A Combined Treatment of BMP2 and Soluble VEGFR1 for the Enhancement of Tendon-Bone Healing by Regulating Injury-Activated Skeletal Stem Cell Lineage.
The American journal of sports medicine
BACKGROUND:Bone morphogenetic protein 2 (BMP2) is an appealing osteogenic and chondrogenic growth factor for promoting tendon-bone healing. Recently, it has been reported that soluble vascular endothelial growth factor (VEGF) receptor 1 (sVEGFR1) (a VEGF receptor antagonist) could enhance BMP2-induced bone repair and cartilage regeneration; thus, their combined application may represent a promising treatment to improve tendon-bone healing. Moreover, BMP2 could stimulate skeletal stem cell (SSC) expansion and formation, which is responsible for wounded tendon-bone interface repair. However, whether the codelivery of BMP2 and sVEGFR1 increases tendon enthesis injury-activated SSCs better than does BMP2 alone needs further research. PURPOSE:To study the effect of BMP2 combined with sVEGFR1 on tendon-bone healing and injury-activated SSC lineage. STUDY DESIGN:Controlled laboratory study. METHODS:A total of 128 C57BL/6 mice that underwent unilateral supraspinatus tendon detachment and repair were randomly assigned to 4 groups: (1) untreated control group; (2) hydrogel group, which received a local injection of the blank hydrogel at the injured site; (3) BMP2 group, which received an injection of hydrogel with BMP2; and (4) BMP2 with sVEGFR1 group, which received an injection of hydrogel with BMP2 and sVEGFR1. Histology, micro-computed tomography, and biomechanical tests were conducted to evaluate tendon-bone healing at 4 and 8 weeks after surgery. In addition, flow cytometry was performed to detect the proportion of SSCs and their downstream differentiated subtypes, including bone, cartilage, and stromal progenitors; osteoprogenitors; and pro-chondrogenic progenitors within supraspinatus tendon enthesis at 1 week postoperatively. RESULTS:The repaired interface in BMP2 with sVEGFR1 group showed a significantly improved collagen fiber continuity, increased fibrocartilage, greater newly formed bone, and elevated mechanical properties compared with the other 3 groups. There were more SSCs; bone, cartilage, and stromal progenitors; osteoprogenitors; and pro-chondrogenic progenitors in the BMP2 with sVEGFR1 group than that in the other groups. CONCLUSION:Our study suggests that the combined delivery of BMP2 and sVEGFR1 could promote tendon-bone healing and stimulate the expansion of SSCs and their downstream progeny within the injured tendon-bone interface. CLINICAL RELEVANCE:Combining BMP2 with sVEGFR1 may be a good clinical treatment for wounded tendon enthesis healing.
10.1177/03635465231225244
BMP-2/TGF-β1 gene insertion into ligament-derived stem cells sheet promotes tendon-bone healing in a mouse.
Biotechnology journal
Bone morphogenetic protein-2 (BMP-2) and transforming growth factor-β1 (TGF-β1) reportedly induce the osteogenic and tenogenic differentiation of anterior cruciate ligament (ACL)-derived stem cells (LDSCs), respectively. However, few studies have investigated the effect of BMP-2/TGF-β1 on the differentiation of LDSC. We developed a BMP-2/TGF-β1 gene insertion into an LDSC cell sheet that promotes tendon-bone healing in a mouse ACL reconstruction (ACLR) model. CD34 LDSCs were isolated from human ACL stump tissues, virally transduced to express BMP-2 or TGF-β1, and then embedded within cell sheets. All mice underwent ACLR using an autograft wrapped with a cell sheet and were randomly divided into three groups: BMP-2-, TGF-β1-, and BMP-2/TGF-β1-transduced. At 4 and 8 weeks, tendon-bone healing was evaluated by micro-CT, biomechanical test, and histological analysis. BMP-2 and TGF-β1 promoted the osteogenic and tenogenic differentiation of LDSC in vitro. BMP-2/TGF-β1-transduced LDSC sheet application contributed to early improvement in mean failure load and graft stiffness, accelerated maturation of the tendon-bone junction, and inhibited bone tunnel widening. Furthermore, reduced M1 macrophage infiltration and a higher M2 macrophage percentage were observed in the BMP-2/TGF-β1-transduced LDSC group. This work demonstrated that BMP-2 and TGF-β1 promoted CD34 LDSCs osteogenic and tenogenic differentiation in vitro and in vivo, which accelerated the tendon-bone healing after ACLR using autografts wrapped with cell sheets in a mouse model.
10.1002/biot.202200470
Autologous Dedifferentiated Osteogenic Bone Marrow Mesenchymal Stem Cells Promote Bone Formation in a Rabbit Model of Anterior Cruciate Ligament Reconstruction versus Bone Marrow Mesenchymal Stem Cells.
Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association
PURPOSE:This study aimed to verify whether transplantation of dedifferentiated osteogenic bone marrow mesenchymal stem cells (De-BMSCs) at the tendon-bone interface could result in more bone formation than BMSC transplantation in anterior cruciate ligament (ACL) reconstruction. METHODS:BMSCs from femur and tibia of New Zealand White rabbit were subjected to osteogenic induction and then cultured in osteogenic factor-free medium; the obtained cell population was termed De-BMSCs. Bilateral ACL reconstruction was performed in 48 adult rabbits. Three groups were established: control group with alginate gel injection, BMSCs group with the BMSCs injection, and De-BMSCs group with the De-BMSCs injection. At week 4 and 12 postoperatively, tendon-bone healing by histologic staining, micro-computed tomography examination, and biomechanical test were evaluated. RESULTS:The expression of α1 chain of type I collagen, osteocalcin, and osteopontin at the tendon-bone interface in the De-BMSCs group was greater than in the control or BMSCs group. The bone volume/total volume by micro-computed tomography scan was significantly greater in the De-BMSCs group than that in the control group (P = .013) or BMSCs group (P = .045) at 4 weeks, and greater than that in the control group (P = .014) or BMSCs group (P = .017) at 12 weeks. The tunnel area was significantly smaller in the De-BMSCs group than in the control group (P = .013) or BMSCs group (P = .044) at 12 weeks. The failure load and stiffness in De-BMSCs group were both significantly enhanced at 4 and 12 weeks than control group or De-BMSCs group. CONCLUSIONS:De-BMSCs transplantation can promote bone formation at the tendon-bone interface better than BMSCs transplantation in ACL reconstruction and increase the early biomechanical strength of the reconstructed ACL CLINICAL RELEVANCE: De-BMSCs transplantation is a potential choice for enhancing early bone formation in the tunnel in ACL reconstruction.
10.1016/j.arthro.2022.01.021
Hyperbaric oxygen therapy enhances graft healing and mechanical properties after anterior cruciate ligament reconstruction: An experimental study in rabbits.
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
Hyperbaric oxygen therapy (HBOT) has proven successful in wound healing. However, its potential effects on anterior cruciate ligament (ACL) injuries remain uncertain. This study aimed to investigate the impact of HBOT on graft healing following ACL reconstruction in rabbits. Male New Zealand rabbits underwent ACL reconstruction and were randomly divided into two groups: the HBOT group and the ambient air group. The HBOT group received 100% oxygen at 2.5 atmospheres absolute for 2 h daily for 5 consecutive days, starting from the first day after surgery. The ambient air group was maintained in normal room air throughout the entire period. After 12 weeks following the surgery, animals were euthanized, and their knees were harvested for analysis. The HBOT group demonstrated superior graft maturation and integration in comparison to the ambient air group, as evidenced by lower graft signal intensity on magnetic resonance imaging, decreased femoral and tibial tunnel size, and higher bone mineral density values on high-resolution peripheral quantitative computed tomography scans. Additionally, biomechanical testing indicated that the HBOT group had greater load to failure and stiffness values than the ambient air group. In conclusion, the adjuvant use of HBOT improved ACL graft maturation and integration, reduced tunnel widening, and enhanced the biomechanical properties of the graft. These results may provide important insights into the potential clinical application of HBOT as a therapeutic intervention to enhance graft healing after ACL reconstruction, paving the way for further research in this area.
10.1002/jor.25787
Effect of Graft Choice for ACL Reconstruction on Clinical Outcomes in Combined ACL and MCL Injuries: Comparison Between Bone-Patellar Tendon-Bone and Hamstring Autografts.
Journal of clinical medicine
The optimal graft, particularly in combined anterior cruciate ligament (ACL) and medial collateral ligament (MCL) injuries, remains controversial. We evaluated the influence of graft choice between bone-patellar tendon-bone (BPTB) and hamstring autografts on clinical outcomes in combined ACL and MCL injuries. This retrospective analysis included patients with concurrent ACL and MCL injuries who underwent single-bundle ACL reconstruction with BPTB (group B) or hamstring (group H) grafts, between 2010 and 2019, with a ≥2-year follow-up. Patients were classified based on the MCL injury grade (I, II, or III). Clinical outcomes were assessed through knee stability evaluations using valgus stress radiographs and the KT-2000 arthrometer, patient-reported outcomes using the International Knee Documentation Committee (IKDC) subjective score and Lysholm score, and radiologic outcomes using the IKDC radiographic grade. The study included 169 patients (group B, 92; group H, 77). No significant between-group differences in knee stability or functional outcomes were found after follow-up. Within the same MCL injury grade, particularly in high-grade MCL injuries, BPTB grafts resulted in significantly better medial stability (side-to-side difference in medial joint opening on valgus stress radiographs: grade II, = 0.006; grade III, = 0.039) and functional outcomes (IKDC subjective score: grade II, = 0.045; grade III, = 0.038) than hamstring grafts. In the hamstring group, higher-grade MCL injuries were associated with worse outcomes (Lysholm knee score, = 0.009; IKDC subjective score, = 0.015). Graft choice in ACL reconstruction with concomitant MCL injuries may affect clinical outcomes, particularly in high-grade MCL injuries. Although both graft types performed similarly overall, BPTB grafts provided superior medial stability and functional results in higher-grade MCL injuries. However, caution is needed when interpreting these results due to limitations such as the small sample size and the lack of randomization in graft selection.
10.3390/jcm13216316
[Research on Runx2 gene induced differentiation of human amniotic mesenchymal stem cells into ligament fibroblasts and promotion of tendon-bone healing in rabbits].
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery
Objective:To investigate whether the Runx2 gene can induce the differentiation of human amniotic mesenchymal stem cells (hAMSCs) to ligament fibroblasts and promote the tendon-bone healing in rabbits. Methods:hAMSCs were isolated from the placentas voluntarily donated from healthy parturients and passaged, and then identified by flow cytometric identification. Adenoviral vectors carrying Runx2 gene (Ad-Runx2) and empty vector adenovirus (Ad-NC) were constructed and viral titer assay; then, the 3rd generation hAMSCs were transfected with Ad-Runx2 (Ad-Runx2 group) or Ad-NC (Ad-NC group). The real-time fluorescence quantitative PCR and Western blot were used to detect Runx2 gene and protein expression to verify the effectiveness of Ad-Runx2 transfection of hAMSCs; and at 3 and 7 days after transfection, real-time fluorescence quantitative PCR was further used to detect the expressions of ligament fibroblast-related genes [vascular endothelial growth factor (VEGF), collagen type Ⅰ, Fibronectin, and Tenascin-C]. The hAMSCs were used as a blank control group. The hAMSCs, hAMSCs transfected with Ad-NC, and hAMSCs were mixed with Matrigel according to the ratio of 1 : 1 and 1 : 2 to construct the cell-scaffold compound. Cell proliferation was detected by cell counting kit 8 (CCK-8) assay, and the corresponding cell-scaffold compound with better proliferation were taken for subsequent animal experiments. Twelve New Zealand white rabbits were randomly divided into 4 groups of sham operation group (Sham group), anterior cruciate ligament reconstruction group (ACLR group), anterior cruciate ligament reconstruction+hAMSCs transfected with Ad-NC-scaffold compound group (Ad-NC group), and anterior cruciate ligament reconstruction+hAMSCs transfected with Ad-Runx2-scaffold compound group (Ad-Runx2 group), with 3 rabbits in each group. After preparing the ACL reconstruction model, the Ad-NC group and the Ad-Runx2 group injected the optimal hAMSCs-Matrigel compunds into the bone channel correspondingly. The samples were taken for gross, histological (HE staining and sirius red staining), and immunofluorescence staining observation at 1 month after operation to evaluate the inflammatory cell infiltration as well as collagen and Tenascin-C content in the ligament tissues. Results:Flow cytometric identification of the isolated cells conformed to the phenotypic characteristics of MSCs. The Runx2 gene was successfully transfected into hAMSCs. Compared with the Ad-NC group, the relative expressions of VEGF and collagen type Ⅰ genes in the Ad-Runx2 group significantly increased at 3 and 7 days after transfection ( <0.05), Fibronectin significantly increased at 3 days ( <0.05), and Tenascin-C significantly increased at 3 days and decreased at 7 days ( <0.05). CCK-8 detection showed that there was no significant difference ( >0.05) in the cell proliferation between groups and between different time points after mixed culture of two ratios. So the cell-scaffold compound constructed in the ratio of 1∶1 was selected for subsequent experiments. Animal experiments showed that at 1 month after operation, the continuity of the grafted tendon was complete in all groups; HE staining showed that the tissue repair in the Ad-Runx2 group was better and there were fewer inflammatory cells when compared with the ACLR group and the Ad-NC group; sirius red staining and immunofluorescence staining showed that the Ad-Runx2 group had more collagen typeⅠ and Ⅲ fibers, tending to form a normal ACL structure. However, the fluorescence intensity of Tenascin-C protein was weakening when compared to the ACLR and Ad-NC groups. Conclusion:Runx2 gene transfection of hAMSCs induces directed differentiation to ligament fibroblasts and promotes tendon-bone healing in reconstructed anterior cruciate ligament in rabbits.
10.7507/1002-1892.202306010
Bone Grafting of the Bone Defects after Harvesting the Bone Patellar Tendon Bone Graft - A Novel Surgical Technique.
Journal of orthopaedic case reports
Introduction:The anterior knee pain is the most common post-operative complaint associated with anterior cruciate ligament reconstruction (ACLR) using bone patellar tendon bone graft. It has been attributed to various factors such as loss of terminal extension, infrapatellar branch neuroma, and also due to the bone harvest site defect itself. Bone grafting of the defects in the patella and tibia has been shown to decrease anterior knee pain. At the same time, it also prevents post-operative stress fractures. Surgical Technique:Numerous bone pieces were produced in the knee joint as a result of the drilling during ACL reconstruction. Using a wash cannula and tissue grasper, all the bone fragments were gathered into a kidney tray. The bony fragments with the saline which were collected in the metal container were allowed to sediment at the bottom. The bone that was sedimented in the metal container was collected by decantation and placed into the bony defects of the patellar and tibial sides. Conclusion:Bone grafting of the defects in the patella and tibia has been shown to decrease anterior knee pain. Our technique is cost-effective as there is no requirement for special instrumentation like coring reamers, and no requirement for allograft or bone substitutes. Second, there is no morbidity associated with autografts harvested from elsewhere, we used the bone generated during the ACLR itself.
10.13107/jocr.2023.v13.i03.3590
Analysis of Graft Types Augmented With an Internal Brace for ACL Reconstruction: A Systematic Review.
The American journal of sports medicine
BACKGROUND:New techniques are being developed to decrease the failure rate of anterior cruciate ligament (ACL) grafts and prevent revision surgery. One such technique involves high-strength suture tape (ST), also referred to as internal bracing. Recent literature has highlighted the use of ST for ACL reconstruction, but no study has compared ST augmentation between graft types. PURPOSE:To compare the use of ST augmentation for ACL reconstruction based on the type of graft used (ie, bone-patellar tendon-bone [BPTB], quadriceps, hamstring). STUDY DESIGN:Systematic review; Level of evidence, 5. METHODS:An online search of multiple databases was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and was completed April 2022 to identify studies related to ST augmentation of ACL grafts. RESULTS:Of 926 studies identified, 10 met inclusion criteria. Five studies (50%) used hamstring tendon (HT), 3 (30%) used quadriceps tendon (QT), 1 (10%) used BPTB, and 1 (10%) used both HT and QT grafts. HT autografts augmented with ST had decreased dynamic and peak elongation (15%-56%), increased load to failure, and increased initial and final dynamic stiffness compared with controls. There was no significant difference in postoperative physical examination findings (range of motion, Lachman, pivot shift), except that ST-augmented grafts had significantly less laxity after surgery compared with HT alone (0.8 vs 1.9 mm; < .05). QT allografts with ST augmentation showed increased graft strength. Human QT autograft studies showed higher Knee injury and Osteoarthritis Outcome Score scores compared with controls. BPTB allografts with ST augmentation had decreased cyclic displacement by 31% ( = .015) and increased load (758 ± 128 N; < .001) and stiffness (156 ± 23 N/mm; = .003) compared with nonaugmented groups. The complication rate was low or showed no increase in the ST augmentation groups compared with control groups. CONCLUSION:HT, QT, and BPTB grafts augmented with ST demonstrate an effective method for ACL reconstruction. All graft types with ST augmentation showed no evidence of clinical disadvantage, with some studies indicating significant biomechanical or clinical advantages compared with conventional ACL reconstruction.
10.1177/03635465231196157
In Vitro Investigation of the Fixation Performance of a Bioabsorbable Magnesium ACL Interference Screw Compared to a Conventional Interference Screw.
Life (Basel, Switzerland)
An anterior cruciate ligament (ACL) reconstruction is a common treatment for patients with ACL rupture that aims to regain pre-injury knee stability and kinematics. During the ACL reconstruction, one method to fix the graft is the use of an interference screw (IS). The IS should provide initial stability and secure the graft during the healing period. In recent years, magnesium has emerged as an alternative material to permanent metal and polymer ISs. In addition, differences in designs, such as the shape of the IS, can influence the fixation performance of the IS. Therefore, in this biomechanical experiment, two different screw designs with two ligament materials were compared in an insertion and a pull-out test at a rate of 1 mm/s. The screw designs were a conventional polymer screw and a magnesium screw. Porcine tendon and nylon rope were used as ligament materials. All tests were performed in polyurethane foam blocks with 15 PCF density (Synbone AG, Switzerland). As a result, both screw designs required an insertion torque of less than 3 Nm. There was a significant difference between the porcine and nylon rope in pull-out tests for each screw design. The magnesium screw had the highest pull-out force at 412.14 ± 50.00 N for porcine tendon and 707.38 ± 21.81 N for nylon rope. There were no significant differences in tunnel widening (narrow-wide ratio) between each ligament material. The magnesium screw showed the lowest narrow-wide tunnel ratio, implying a better ability to compress the graft to the tunnel. In conclusion, a more optimized magnesium IS design resulted in better graft fixation and an improved ACL reconstruction outcome.
10.3390/life13020484
Trends in Anterior Cruciate Ligament Reconstruction Techniques and Postoperative Care Among Leaders in the Field: A Survey of the Herodicus Society.
Orthopaedic journal of sports medicine
Background:Despite a growing body of literature regarding anterior cruciate ligament reconstruction (ACLR), there remains a wide diversity in surgical technique and clinical practice across providers. Purpose:To (1) describe current ACLR practice preferences among members of the Herodicus society and (2) determine whether these preferences are influenced by years in practice and overall surgical volume. Study Design:Cross-sectional study. Methods:A 24-question survey investigating surgeons' practices and preferred ACLR surgical techniques was sent via email to all active Herodicus Society members. Survey responses were subdivided by years of experience and overall ACLR annual case volume. Descriptive statistics were compiled and chi-square testing was utilized to determine the significance of experience and case volume on survey responses. Results:Of the 113 invited Herodicus Society members who perform ACLR, 69 (61%) completed the survey. Respondents had a mean ± SD of 30.9 ± 9.8 years of experience in clinical practice and performed a mean of 96.0 ± 50.7 primary and 21.6 ± 16.9 revision ACLR annually. Of revision cases, 72.1% were performed using a single-stage technique. Mean frequency of graft usage by surgeon was bone-patellar tendon-bone autograft (58.6%), quadriceps autograft (14.6%), hamstring tendon autograft (14.0%), and allograft (11.8%). The plurality of surgeons responded that they used anterolateral augmentation "rarely" in primary ACLR (39.1%) and "sometimes" in revision ACLR (31.9%), with the majority performing lateral extra-articular tenodesis (66.7%) rather than anterolateral ligament reconstruction (14.5%). Most surgeons would not allow a 20-year-old football player to return before 7 months after ACLR (71.0%) but highly valued return-to-sports testing to determine readiness (94.2%). Higher volume surgeons performed single-stage revision ACLR at a significantly higher rate (79.8% vs 62.9%, = .02) and significantly differed in return-to-sports criteria, with a greater proportion relying primarily on biometric testing ( = .01). Conclusion:The survey demonstrated that, in the Herodicus Society, a wide range of preferences exist regarding ACLR surgical technique. Bone-patellar tendon-bone autograft is the most frequent primary ACLR graft choice. Most participants have not embraced newer techniques such as anterolateral or suture tape augmentation. Return to sports is generally not allowed before 7 months and heavily factors-in return-to-sports testing metrics, suggesting that purely time-based criteria for return to sports is not modern practice among elite sports medicine surgeons.
10.1177/23259671241274770
Sustainability studies in orthopaedic surgery: The carbon footprint of anterior cruciate ligament reconstruction depends on graft choice.
Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA
PURPOSE:Environmental sustainability in medicine is a growing concern. Determining the carbon footprint of medical procedures may aid in selecting a less impactful technique moving forward. The purpose of this study was to understand the environmental impact of different anterior cruciate ligament reconstruction techniques, for which there is no consensus in terms of optimal graft. METHODS:A life cycle analysis of different anterior cruciate ligament reconstruction techniques was performed. These included quadrupled semitendinosus graft, bone-patellar tendon-bone graft, iliotibial band augmented with gracilis graft, doubled semitendinosus and doubled gracilis graft, and quadriceps tendon graft. All procedures were systematically paired with a lateral extra-articular procedure. The study was conducted in a specialised centre using surgeon preference cards, with the help of a dedicated organisation for calculation according to the ISO 14044 standard. The primary outcome measure was the carbon footprint of each of the five techniques. Secondary outcomes included other environmental impact indicators, including human carcinogenic toxicity and mineral resource scarcity, among others, based on the ReCiPe 2016 midpoint guideline. The analysis had three scopes, each encompassing varying numbers of processes: graft implantation, full procedure, and entire environmental impact, from medical prescription to patient discharge. Results were reported as percentage increases compared to the graft technique with the lowest environmental impact. RESULTS:It was demonstrated that the surgical procedure itself accounted for <40% of the life cycle, with arthroscopy being 88% of surgery's GHG emissions, and scrubbing and draping contributing 39% to the carbon footprint. The iliotibial band augmented with gracilis tendon technique had the lowest carbon footprint (0.199 Kg Co eq), and the least impact in most categories at all scopes of the life cycle analysis. Using this technique as a reference, in terms of graft implantation, it was determined that extensor mechanism grafts had the highest carbon footprint (300% higher than the reference). Greater scopes showed a similar trend, with percentage differences decreasing significantly, reaching 1-3% when considering the entire environmental impact for most categories. Nevertheless, among the aforementioned factors of the ReCiPe 2016 guidelines, the semitendinosus graft paried with a lateral extra-articular procedure displayed greater difference in human carcinogenic toxicity and mineral resource scarcity (6% and 10% respectively) compared to the reference. The individual processes with the highest impact were also highlighted. CONCLUSIONS:In the institution where the study was conducted, the studied iliotibial band graft option was found to have the lowest environmental impact. Such analyses of standardised procedures can be replicated in individual institutions in order to determine their environmental impact. Identification of procedures with comparable results and differing environmental consequences may influence the future decision-making process. LEVEL OF EVIDENCE:Level II, prospective cohort study.
10.1002/ksa.12035
Development of a novel geometrically-parametric patient-specific finite element model for anterior cruciate ligament reconstruction.
The Knee
PURPOSE:A personalized model of the knee joint, with adjustable effective geometric parameters for the transplanted autograft diameter in Anterior Cruciate Ligament Reconstruction (ACLR) using the bone-patella-tendon-bone (BPTB) technique, has been developed. The model will assist researchers in understanding how different graft sizes impact a patient's recovery over time. METHODS:The study involved selecting a group of individuals without knee injuries and one patient who had undergone knee surgery. Gait analysis was conducted on the control group and the patient at various time points. A 3D model of the knee joint was created using medical images of the patient. Forces and torques obtained from the gait analysis were applied to the model to perform finite element analysis. RESULTS:The results of the finite element (FE) analysis, along with kinetic data from both groups, indicate that models with diameters of 7.5 mm and 12 mm improved joint motion during follow-up after ACLR. Additionally, a comparison of the stress applied to the ACL model revealed that a 12 mm autograft diameter showed a more favorable trend in patient recovery during the three follow-up intervals after ACL reconstruction surgery. CONCLUSION:The development of a personalized parametric model with adjustable geometric parameters in ACLR, such as the transplanted autograft diameter, as presented in this study, along with FE using the patient's kinetic data, allows for the examination and selection of an appropriate autograft diameter for Patella Tendon grafting. This can help reduce stress on the autograft and prevent damage to other knee joint tissues after ACLR.
10.1016/j.knee.2024.07.020
Sheathed fixation improves BASHTI technique in an anterior cruciate ligament reconstruction.
Proceedings of the Institution of Mechanical Engineers. Part H, Journal of engineering in medicine
Bone and Site Hold Tendon Inside (BASHTI) technique is an implant-less surgical methodology used for anterior cruciate ligament (ACL) reconstruction. It has some clinical advantages, such as speeding up the healing process. Since the force required to insert the core bone inside the tunnel may damage the core bone and affect the fixation process, the study aims to investigate the strength of fixation of BASHTI technique using proposed sheathed core bones. Experimental tests were performed to evaluate the biomechanical strength of the fixation. Synthetic bone combined with bovine tendons as a graft was used. Polymers were used to create the sheath for mechanical testing. The results showed that fixation strength and stiffness in PTFE sheath with 0.1 mm were 343.86 N and 114.62 N/mm and in PVC sheath with similar thickness, 235.95 N, and 93.36 N/mm. Subsequently, 0.2 mm PTFE sheaths were tested in two different sections: incomplete fixation and complete fixation. The strength and stiffness of the first section were 221.6 N and 66.99 N/mm and for the second section 420.02 N and 126.16 N/mm. Using sheath facilitates the fixation process in BASHTI technique. The 0.1 mm PTFE sheath and 0.2 mm PTFE sheath with complete fixation provide higher fixation strength than other groups. The outcome showed that engaged length has a direct effect on the fixation strength. The BASHTI technique offers an implant-less organic ACL reconstruction method that can improve the fixation method and speed up the healing process.
10.1177/09544119231153198
Additional suture augmentation to anterior cruciate ligament reconstruction with hamstring autografts bring no benefits to clinical results, graft maturation and graft-bone interface healing.
BMC musculoskeletal disorders
BACKGROUND:From the perspective of graft protection and early rehabilitation during the maturation and remodeling phases of graft healing, suture augmentation (SA) for anterior cruciate ligament reconstruction (ACLR) has attracted more and more attention. STUDY DESIGN:Retrospective study. PURPOSE:To determine whether the additional SA affects clinical results, graft maturation and graft-bone interface healing during two years follow-up after ACLR. METHODS:20 ACLRs with additional SA (ACLR-SA group) and 20 ACLRs without additional SA (ACLR group) were performed between January 2020 and December 2021 by the same surgeon and were retrospectively analyzed. Pre- and postoperative International Knee Documentation Committee (IKDC) scores, Lysholm scores, graft failure and reoperation were evaluated. The signal/noise quotient (SNQ) of autografts and the signal intensity of graft-bone interface were analyzed. All 40 patients in ACLR-SA group and ACLR group completed 2-years follow-up. RESULTS:There was no patient in the two cohorts experienced graft failure and reoperation. The postoperative IKDC and Lysholm scores have been significantly improved compared with preoperative scored in both ACLR-SA group and ACLR group, however, there was no significant difference between two groups. The SNQ of proximal graft of ACLR-SA group (14.78 ± 8.62 vs. 8.1 ± 5.5, p = 0.041) was significantly greater while the grades of graft-bone interface healing of posterior tibial was significantly lower than that of ACLR group at 1-year postoperatively (p = 0.03), respectively. There were no significant differences between the two groups of the SNQ of proximal, distal medial graft segments, and the graft-bone interface healing grades of anterior femoral, posterior femoral, anterior tibial and posterior tibial at other time points (p>0.05). CONCLUSIONS:The additional SA in ACLR had no effect on IKDC scores, Lysholm scores, graft maturation and graft-bone interface healing at 2-year postoperatively. Our research does not support the routine use of SA in ACLR.
10.1186/s12891-024-07426-w
Editorial Commentary: Anterior Cruciate Ligament Reconstruction or Repair With Suture Augmentation Allows Early Rehabilitation: Collagen Co-braid Sutures May Improve Biological Integration.
Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association
Suture augmentation in anterior cruciate ligament (ACL) reconstruction has the potential to combine improved long-term stability and high functional outcomes with accelerated rehabilitation, enhancing the biomechanical properties of the graft and reducing the risk of graft failure, particularly during the critical early phases of rehabilitation. Suture augmentation, applied to either ACL reconstruction (ACLR) or primary repair, introduces a "safety belt" synergistically sharing loads acting on the graft or repair. Several biomechanical studies using different autologous grafts for ACLR, as well as studies on ACL repair, have shown that suture augmentation enhances strength and prevents elongation of the graft or ligament. Suture augmentation can protect the graft-brace integrity under loads of 350 N, and reduces cyclic displacement by up to 31% compared with conventional ACLR using bone-patellar tendon-bone allograft. Perhaps, as above, the greatest advantage of suture augmentation is allowing early rehabilitation. Assuming successful ligamentization of the graft, the graft itself should stabilize the knee joint, thereby diminishing the long-term benefit of suture augmentation. In practice, we use suture augmentation to support immediate postoperative mobilization and weight bearing, enabling safe and early rehabilitation while minimizing the risk of failure. Regarding the oft-mentioned risk of overconstraint, this is not supported by biomechanical studies or clinical experience. The recent introduction of collagen co-braid sutures for suture augmentation offers 2 distinct advantages: first, potentially improved biocompatibility, and second, gradual biological integration allowing suture degradation over time.
10.1016/j.arthro.2024.10.022
Hamstring autografts demonstrate either similar or inferior outcomes to quadriceps or bone-patellar tendon-bone autografts in revision anterior cruciate ligament reconstruction: A systematic review of comparative studies.
Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA
PURPOSE:To evaluate the clinical outcomes in patients undergoing revision anterior cruciate ligament reconstruction (r-ACLR) using hamstring tendon (HT) autografts with those using either quadriceps tendon (QT) or bone-patellar tendon-bone (BPTB) autografts or allografts. METHODS:Three databases were searched on 8 August 2023. The authors adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Revised Assessment of Multiple Systematic Reviews (R-AMSTAR) guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. Data on demographics, surgical details, patient-reported outcome measures (PROMs), rates of instability, failure and return to sport (RTS) were extracted. RESULTS:Eleven studies comprising 859 patients were included in this review. Five studies compared HT and QT autografts. One study each reported greater IKDC scores (p = 0.04) and Tegner scores (p = 0.04) in the QT group, while one study each reported higher anterior translation (p = 0.04), rates of positive pivot shift (p = 0.03) and rates of failure (p = 0.03) in the HT group. Six studies compared HT and BPTB autografts with one study each reporting greater Lysholm scores (p = 0.02) and less side-to-side anterior laxity (p < 0.01) in the BPTB group. Two studies compared HT autografts with allografts with only one study reporting a faster time to RTS in the HT group than the allograft group (p < 0.001). All other comparisons were not significant. CONCLUSIONS:HT autografts result in either similar or inferior outcomes in r-ACLR when compared to QT or BPTB autograft options. Allografts resulted in similar outcomes to HT autografts apart from greater time to RTS for r-ACLR. LEVEL OF EVIDENCE:Level III.
10.1002/ksa.12366
Multiphasic bone-ligament-bone integrated scaffold enhances ligamentization and graft-bone integration after anterior cruciate ligament reconstruction.
Bioactive materials
The escalating prevalence of anterior cruciate ligament (ACL) injuries in sports necessitates innovative strategies for ACL reconstruction. In this study, we propose a multiphasic bone-ligament-bone (BLB) integrated scaffold as a potential solution. The BLB scaffold comprised two polylactic acid (PLA)/deferoxamine (DFO)@mesoporous hydroxyapatite (MHA) thermally induced phase separation (TIPS) scaffolds bridged by silk fibroin (SF)/connective tissue growth factor (CTGF)@Poly(l-lactide-co-ε-caprolactone) (PLCL) nanofiber yarn braided scaffold. This combination mimics the native architecture of the ACL tissue. The mechanical properties of the BLB scaffolds were determined to be compatible with the human ACL. experiments demonstrated that CTGF induced the expression of ligament-related genes, while TIPS scaffolds loaded with MHA and DFO enhanced the osteogenic-related gene expression of bone marrow stem cells (BMSCs) and promoted the migration and tubular formation of human umbilical vein endothelial cells (HUVECs). In rabbit models, the BLB scaffold efficiently facilitated ligamentization and graft-bone integration processes by providing bioactive substances. The double delivery of DFO and calcium ions by the BLB scaffold synergistically promoted bone regeneration, while CTGF improved collagen formation and ligament healing. Collectively, the findings indicate that the BLB scaffold exhibits substantial promise for ACL reconstruction. Additional investigation and advancement of this scaffold may yield enhanced results in the management of ACL injuries.
10.1016/j.bioactmat.2023.08.004
Current trends in graft choice for anterior cruciate ligament reconstruction - part I: anatomy, biomechanics, graft incorporation and fixation.
Journal of experimental orthopaedics
Graft selection in anterior cruciate ligament (ACL) reconstruction is critical, as it remains one of the most easily adjustable factors affecting graft rupture and reoperation rates. Commonly used autografts, including hamstring tendon, quadriceps tendon and bone-patellar-tendon-bone, are reported to be biomechanically equivalent or superior compared to the native ACL. Despite this, such grafts are unable to perfectly replicate the complex anatomical and histological characteristics of the native ACL. While there remains inconclusive evidence as to the superiority of one autograft in terms of graft incorporation and maturity, allografts appear to demonstrate slower incorporation and maturity compared to autografts. Graft fixation also affects graft properties and subsequent outcomes, with each technique having unique advantages and disadvantages that should be carefully considered during graft selection.
10.1186/s40634-023-00600-4
Investigation of the medium-term effect of osteoprotegerin/bone morphogenetic protein 2 combining with collagen sponges on tendon-bone healing in a rabbit.
Journal of orthopaedic surgery (Hong Kong)
BACKGROUND:Osteoprotegerin (OPG) and bone morphogenetic protein-2 (BMP-2) could be administered sequentially to promote tendon-bone healing. There remain several unresolved issues in our previously published study: a) the release kinetics of OPG/BMP-2 from the OPG/BMP-2/collagen sponge (CS) combination in vitro remained unclear; b) the medium-term effect of the OPG/BMP-2/CS combination was not analyzed. Hence, we design this study to address the issues mentioned above. METHODS:30 rabbits undergoing anterior cruciate ligament reconstruction (ACLR) with an Achilles tendon autograft randomly received one of the 3 delivery at the femoral and tibial tunnels: OPG/BMP-2, OPG/BMP-2/CS combination, and nothing (blank control). At 8 and 24 weeks post-surgery, the biomechanical tests and histologic analysis were used to evaluate the tendon-bone healing. RESULTS:In mechanical tests, the OPG/BMP-2/CS group showed a higher final failure load and stiffness than the other groups at 8 and 24 weeks. Additionally, the maximum stretching distance showed a decreasing trend. The mechanical failure pattern of samples shifted from a tunnel pull-away to a graft midsubstance rupture after OPG/BMP-2/CS-treated. From histological analysis, the OPG/BMP-2/CS treatment increased the amount of collagen fibers (collagen I and II) and promoted fibrocartilage attachment. CONCLUSION:CS as a carrier promotes the medium-term effect of OPG and BMP-2 on tendon-bone healing at the tendon-bone interface in a rabbit ACLR model. OPG, BMP-2 and CS were already applied in several clinical practice, but a further study of clinic use of OPG/BMP-2/CS is still needed.
10.1177/10225536231163467
Slit Guidance Ligand 3 (SLIT3) Loaded in Hydrogel Microparticles Enhances the Tendon-Bone Healing through Promotion of Type-H Vessel Formation: An Experimental Study in Mice.
International journal of molecular sciences
Poor tendon-bone interface (TBI) integration is one of the major causes contributing to unsatisfactory healing quality in patients after anterior cruciate ligament (ACL) reconstruction. Type H vessels have been recently found to closely modulate bone formation via regulation of the osteo-angiogenic crosstalk, so the strategies favoring type H vessel formation may be promising therapeutic approaches for improved graft osteointegration. In this study, we reported for the first time the treatment outcome of slit guidance ligand 3 (slit3), a novel proangiogenic factor favoring type H vessel formation, in TBI healing in mice with ACL reconstruction. The mice (n = 87) were divided into three groups for various treatments: hydrogel microparticles (HMP, control group), slit3@HMP, and slit3 neutralizing antibody@HMP (slit3-AB@HMP). Histological analysis, gait performance, radiographic measurement, and biomechanical testing were performed to assess the TBI healing quality. Increased bony ingrowth and reduced fibrous scar tissue was formed at the TBI in the slit3@HMP group when compared to the HMP group. Meanwhile, the slit3-AB@HMP inhibited the osseous ingrowth and increased fibrous scar tissue formation relative to the HMP group. Compared to the HMP group, the slit3@HMP favored type H vessel formation at the TBI while the slit3-AB@HMP impeded it. According to micro-CT assessment, compared to the HMP group, the slit3@HMP significantly increased the peri-tunnel bone mass while the slit3-AB@HMP significantly reduced the peri-tunnel bone mass. The mice in the slit3@HMP group showed the best gait performance in terms of stance time, stride length, paw print area, and stance pressure. Dynamic laxity measurement and tensile testing showed the slit3@HMP group exhibited significantly reduced laxity displacement and improved failure load and stiffness relative to the other two groups. Collectively, the injection of slit3 could be used to enhance tendon-bone integration, which may be ascribed to modulation of angiogenesis-osteogenesis crosstalk coupled by type H vessels.
10.3390/ijms241713638
Scaffold-induced compression enhances ligamentization potential of decellularized tendon graft reseeded with ACL-derived cells.
iScience
Anterior cruciate ligament (ACL) reconstruction is often performed using a tendon graft. However, the predominant synthesis of fibrotic scar tissue (type III collagen) occurs during the healing process of the tendon graft, resulting in a significantly lower mechanical strength than that of normal ACL tissue. In this study, ACL-derived cells were reseeded to the tendon graft, and scaffold-induced compression was applied to test whether the compressive force results in superior cell survival and integration. Given nanofiber polycaprolactone (PCL) scaffold-induced compression, ACL-derived cells reseeded to a tendon graft demonstrated superior cell survival and integration and resulted in higher gene expression levels of type I collagen compared to non-compressed cell-allograft composites . Translocation of Yes-associated protein (YAP) into the nucleus was correlated with higher expression of type I collagen in the compression group. These data support the hypothesis of a potential role of mechanotransduction in the ligamentization process.
10.1016/j.isci.2023.108521
Biomimetic Intrafibrillar Mineralization of Native Tendon for Soft-Hard Interface Integration by Infiltration of Amorphous Calcium Phosphate Precursors.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
Soft and hard tissues possess distinct biological properties. Integrating the soft-hard interface is difficult due to the inherent non-osteogenesis of soft tissue, especially of anterior cruciate ligament and rotator cuff reconstruction. This property makes it difficult for tendons to be mineralized and integrated with bone in vivo. To overcome this challenge, a biomimetic mineralization strategy is employed to engineer mineralized tendons. The strategy involved infiltrating amorphous calcium phosphate precursors into collagen fibrils, resulting in hydroxyapatite deposition along the c-axis. The mineralized tendon presented characteristics similar to bone tissue and induced osteogenic differentiation of mesenchymal stem cells. Additionally, the interface between the newly formed bone and tendon is serrated, suggesting a superb integration between the two tissues. This strategy allows for biomineralization of tendon collagen and replicating the hallmarks of the bone matrix and extracellular niche, including nanostructure and inherent osteoinductive properties, ultimately facilitating the integration of soft and hard tissues.
10.1002/advs.202304216
Enhancing tendon-bone integration and healing with advanced multi-layer nanofiber-reinforced 3D scaffolds for acellular tendon complexes.
Materials today. Bio
Advancements in tissue engineering are crucial for successfully healing tendon-bone connections, especially in situations like anterior cruciate ligament (ACL) restoration. This study presents a new and innovative three-dimensional scaffold, reinforced with nanofibers, that is specifically intended for acellular tendon complexes. The scaffold consists of a distinct layered arrangement comprising an acellular tendon core, a middle layer of polyurethane/type I collagen (PU/Col I) yarn, and an outside layer of poly (L-lactic acid)/bioactive glass (PLLA/BG) nanofiber membrane. Every layer is designed to fulfill specific yet harmonious purposes. The acellular tendon core is a solid structural base and a favorable environment for tendon cell functions, resulting in considerable tensile strength. The central PU/Col I yarn layer is vital in promoting the tendinogenic differentiation of stem cells derived from tendons and increasing the expression of critical tendinogenic factors. The external PLLA/BG nanofiber membrane fosters the process of bone marrow mesenchymal stem cells differentiating into bone cells and enhances the expression of markers associated with bone formation. Our scaffold's biocompatibility and multi-functional design were confirmed through extensive evaluations, such as histological staining and biomechanical analyses. These assessments combined showed notable enhancements in ACL repair and healing. This study emphasizes the promise of multi-layered nanofiber scaffolds in orthopedic tissue engineering and also introduces new possibilities for the creation of improved materials for regenerating the tendon-bone interface.
10.1016/j.mtbio.2024.101099
Synovium-Derived Mesenchymal Stem Cell-Based Scaffold-Free Fibrocartilage Engineering for Bone-Tendon Interface Healing in an Anterior Cruciate Ligament Reconstruction Model.
Tissue engineering and regenerative medicine
BACKGROUND:Current tendon and ligament reconstruction surgeries rely on scar tissue healing which differs from native bone-to-tendon interface (BTI) tissue. We aimed to engineer Synovium-derived mesenchymal stem cells (Sy-MSCs) based scaffold-free fibrocartilage constructs and investigate in vivo bone-tendon interface (BTI) healing efficacy in a rat anterior cruciate ligament (ACL) reconstruction model. METHODS:Sy-MSCs were isolated from knee joint of rats. Scaffold-free sy-MSC constructs were fabricated and cultured in differentiation media including TGF-β-only, CTGF-only, and TGF-β + CTGF. Collagenase treatment on tendon grafts was optimized to improve cell-to-graft integration. The effects of fibrocartilage differentiation and collagenase treatment on BTI integration was assessed by conducting histological staining, cell adhesion assay, and tensile testing. Finally, histological and biomechanical analyses were used to evaluate in vivo efficacy of fibrocartilage construct in a rat ACL reconstruction model. RESULTS:Fibrocartilage-like features were observed with in the scaffold-free sy-MSC constructs when applying TGF-β and CTGF concurrently. Fifteen minutes collagenase treatment increased cellular attachment 1.9-fold compared to the Control group without affecting tensile strength. The failure stress was highest in the Col + D + group (22.494 ± 13.74 Kpa) compared to other groups at integration analysis in vitro. The ACL Recon + FC group exhibited a significant 88% increase in estimated stiffness (p = 0.0102) compared to the ACL Recon group at the 4-week postoperative period. CONCLUSION:Scaffold-free, fibrocartilage engineering together with tendon collagenase treatment enhanced fibrocartilaginous BTI healing in ACL reconstruction.
10.1007/s13770-023-00593-2
Kartogenin-loaded polyvinyl alcohol/nano-hydroxyapatite composite hydrogel promotes tendon-bone healing in rabbits after anterior cruciate ligament reconstruction.
Journal of biomedical materials research. Part A
Accumulating evidence supports the role of cartilage tissue engineering in cartilage defect repair, but the biological function has yet to be fully explained. In this work, kartogenin (KGN), an emerging chondroinductive nonprotein small molecule, was incorporated into a composite hydrogel of polyvinyl alcohol/nano-hydroxyapatite (PVA/n-HA) to fabricate an appropriate microenvironment for tendon-bone healing after anterior cruciate ligament (ACL) reconstruction. KGN/PVA/n-HA composite hydrogel scaffolds were prepared by in situ synthesis and physical adsorption, followed by characterization under a scanning electron microscope. The scaffolds were transplanted into healthy New Zealand White (NZW) rabbits. It was confirmed that KGN/PVA/n-HA scaffolds were successfully prepared and exhibited good supporting properties and excellent biocompatibility. Unilateral ACL reconstruction was constructed with tendon autograft in NZW rabbits, and the morphology and diameter of collagen fiber were analyzed. The scaffolds were shown to promote ACL growth and collagen fiber formation. Furthermore, microcomputerized tomography analysis and bone formation histology were performed to detect new bone formation. KGN/PVA/n-HA scaffolds effectively alleviated cartilage damage and prevented the occurrence of osteoarthritis. Meanwhile, ligament-bone healing and bone formation were observed in the presence of KGN/PVA/n-HA scaffolds. In conclusion, these results suggest that the KGN/PVA/n-HA scaffolds can facilitate tendon-bone healing after ACL reconstruction and might be considered novel hydrogel biomaterials in cartilage tissue engineering.
10.1002/jbm.a.37605
No Clinically Significant Differences in Outcomes After Anterior Cruciate Ligament Reconstruction When Comparing Quadriceps, Bone-Patellar Tendon-Bone, and Hamstring Autografts of 9 mm or Greater.
Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association
PURPOSE:To determine whether there are patient-reported outcome differences in bone-patellar tendon-bone (BPTB), quadriceps tendon (QT), and hamstring (HS) grafts of comparable size. METHODS:We performed a retrospective analysis of global registry data to include all patients who had an anterior cruciate ligament reconstruction with BPTB, QT, or HS autograft of at least 9 mm in diameter between 2010 and 2021 with complete 1- and 2-year outcome scores. We compared 1- and 2-year postoperative outcome scores (visual analog scale [VAS], Knee Injury and Osteoarthritis Outcome Score [KOOS] pain, Marx Activity Rating Scale [MARS], Veterans RAND 12-Item Health Survey [VR-12]) between BPTB, QT, and HS of the same size graft. RESULTS:In total, 2,318 subjects were included in the analysis, and all graft types showed improved patient-reported outcome measures at 1 and 2 years postoperatively when compared with baseline. The KOOS pain score for the BPTB group was significantly better than the HS (between-group difference = 2.71, P < .01) and QT (between-group difference = 2.51, P < .01) groups at 1 year, and the BPTB group was better than HS (between-group difference = 1.88, P < .01) at 2 years. However, the differences were small and not clinically meaningful. When we compared graft type, there were no differences in the percentage of patients who reached Minimal clinically important difference, or clinical scores VAS or MARS at 2-year follow-up. CONCLUSIONS:There is no clinically meaningful difference in KOOS-pain, VR-12, VAS, and MARS at 1 and 2 years postoperatively in patients having anterior cruciate ligament reconstruction with BPTB, HS, or QT if graft size is at least 9 mm in diameter. LEVEL OF EVIDENCE:Level III, retrospective comparative study.
10.1016/j.arthro.2024.08.015
Editorial Commentary: Analysis of Practice Patterns and Changes for Anterior Cruciate Ligament Surgery Document the Past and Present, but High-Quality Data Should Inform the Future.
Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association
Trends in practice patterns for anterior cruciate ligament surgery can give us a real-world look at what surgeons are actually doing. When large institutional studies show changing practice patterns over time, we can use those data to help benchmark our own practices. Innovations are inspired by colleagues, published literature, and industry, and not all innovation is positive. A return to independent drilling of the femoral and tibial tunnels reverses a single-incision trend that was less anatomic. Although hamstring tendon grafts are a popular graft choice, hamstring tendon grafts are associated with greater revision rates, and high-volume surgeons prefer bone-patellar tendon-bone and quadriceps tendon and autografts in general. Additional data are required to determine the benefit of quadriceps tendon and of lateral extra-articular tenodesis augmentation of anterior cruciate ligament reconstruction. Although a first step is to identify current practice patterns, the most important step is to develop high-quality outcome data, which can be used to inform surgeons so they can individualize and optimize surgery for their patients.
10.1016/j.arthro.2024.05.015
Editorial Commentary: Quadrupled Semitendinosus Autograft Is a Suitable Graft Choice for Anterior Cruciate Reconstruction, Regardless of Diameter, in Patients With Lower Risk for Rerupture.
Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association
Multiple options exist for anterior cruciate ligament reconstruction autografts, including bone-patellar tendon-bone, quadriceps tendon, and hamstring tendon (HT). A variant among HT options is quadrupled semitendinosus autograft. In addition, smaller graft diameter (<8 mm) has been associated with failure of HT anterior cruciate ligament reconstruction. However, recent research shows that quadrupled semitendinosus autograft diameters <8 mm are not correlated with a higher rerupture rate in older patients. While among individuals with a lower risk of rerupture, graft diameter does not significantly alter graft rupture rates, and a smaller-diameter soft tissue graft is safe to use in the low-risk population, caution is required when applying this dogma to patients who are younger than 21 years or play higher-risk sports. In such patients, a reliable option is bone-patellar tendon-bone autograft and/or adding a secondary stabilizing procedure such as anterolateral ligament reconstruction or lateral extra-articular tenodesis. Finally, recent research shows there is little utility in trying to predict graft size prior to surgery.
10.1016/j.arthro.2024.09.031
Total flavonoids of Rhizoma drynariae improves tendon-bone healing for anterior cruciate ligament reconstruction in mice and promotes the osteogenic differentiation of bone mesenchymal stem cells by the ERR1/2-Gga1-TGF-β/MAPK pathway.
Environmental toxicology
BACKGROUND:Total flavonoids of Rhizoma drynariae (TFRD) is broadly used in the treatment of orthopedic diseases. Nevertheless, the effects and underlying mechanism of TFRD on tendon-bone healing after anterior cruciate ligament reconstruction (ACLR) remain unclear. METHODS:The ACLR mouse model was established. Hematoxylin and Eosin (HE) staining was used for histological analysis of tendon-bone healing. Western blot was utilized to detect the levels of osteogenic related factors (ALP, OCN, RUNX2). The viability and alkaline phosphatase (ALP) activity of bone mesenchymal stem cells (BMSCs) were determined by Cell Counting Kit-8 (CCK-8) and ALP assays. The interaction of estrogen related receptor alpha (ESRRA), estrogen related receptor beta (ESRRB), and golgi-localized γ-ear containing ADP ribosylation factor-binding protein 1 (Gga1) was detected by luciferase reporter assays. The levels of important proteins on the TGF-β/MAPK pathway were measured by western blot. RESULTS:TFRD improved tendon-bone healing, restored biomechanics of ACLR mice and activated the TGF-β/MAPK pathway. TFRD treatment also enhanced the viability and osteogenic differentiation of BMSCs in vitro. Then, we demonstrated that TFRD targeted ESRRA and ESRRB to transcriptionally activate Gga1 expression. Knockdown of ESRRA, ESRRB, or Gga1 suppressed the viability and osteogenic differentiation of TFRD-induced BMSCs, which was revealed to be restored by Gga1 overexpression. The overexpression of ESRRA, ESRRB, or Gga1 was demonstrated to promote the BMSC viability and osteogenic differentiation. TGF-β1 treatment can reverse the impact of Gga1 inhibition on osteogenic differentiation in TFRD-induced BMSCs. CONCLUSION:TFRD improves tendon-bone healing in ACLR mouse models and facilitates the osteogenic differentiation of BMSCs through the ERR1/2-Gga1-TGF-β/MAPK pathway, which might deepen our understanding of the underlying mechanism of TFRD in tendon-bone healing.
10.1002/tox.23955
[Effect of Kartogenin combined with adipose-derived stem cells on tendon-bone healing after anterior cruciate ligament reconstruction].
Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery
Objective:To investigate the effect of Kartogenin (KGN) combined with adipose-derived stem cells (ADSCs) on tendon-bone healing after anterior cruciate ligament (ACL) reconstruction in rabbits. Methods:After the primary ADSCs were cultured by passaging, the 3rd generation cells were cultured with 10 μmol/L KGN solution for 72 hours. The supernatant of KGN-ADSCs was harvested and mixed with fibrin glue at a ratio of 1∶1; the 3rd generation ADSCs were mixed with fibrin glue as a control. Eighty adult New Zealand white rabbits were taken and randomly divided into 4 groups: saline group (group A), ADSCs group (group B), KGN-ADSCs group (group C), and sham-operated group (group D). After the ACL reconstruction model was prepared in groups A-C, the saline, the mixture of ADSCs and fibrin glue, and the mixture of supernatant of KGN-ADSCs and fibrin glue were injected into the tendon-bone interface and tendon gap, respectively. ACL was only exposed without other treatment in group D. The general conditions of the animals were observed after operation. At 6 and 12 weeks, the tendon-bone interface tissues and ACL specimens were taken and the tendon-bone healing was observed by HE staining, c-Jun N-terminal kinase (JNK) immunohistochemical staining, and TUNEL apoptosis assay. The fibroblasts were counted, and the positive expression rate of JNK protein and apoptosis index (AI) were measured. At the same time point, the tensile strength test was performed to measure the maximum load and the maximum tensile distance to observe the biomechanical properties. Results:Twenty-eight rabbits were excluded from the study due to incision infection or death, and finally 12, 12, 12, and 16 rabbits in groups A-D were included in the study, respectively. After operation, the tendon-bone interface of groups A and B healed poorly, while group C healed well. At 6 and 12 weeks, the number of fibroblasts and positive expression rate of JNK protein in group C were significantly higher than those of groups A, B, and D (<0.05). Compared with 6 weeks, the number of fibroblasts gradually decreased and the positive expression rate of JNK protein and AI decreased in group C at 12 weeks after operation, with significant differences (<0.05). Biomechanical tests showed that the maximum loads at 6 and 12 weeks after operation in group C were higher than in groups A and B, but lower than those in group D, while the maximum tensile distance results were opposite, but the differences between groups were significant (<0.05). Conclusion:After ACL reconstruction, local injection of a mixture of KGN-ADSCs and fibrin glue can promote the tendon-bone healing and enhance the mechanical strength and tensile resistance of the tendon-bone interface.
10.7507/1002-1892.202305011
Allograft to bone-tunnel integration in a canine anterior cruciate ligament reconstruction model: a comparison study of allograft preparation methods.
Journal of orthopaedic surgery and research
The procedure of anterior cruciate ligament (ACL) allograft preparation can be divided into fresh-frozen method (FF-allograft) or freeze-dried method (FD-allograft). This study aims to biomechanically and histologically compare the graft to bone tunnel integration between the two allografts. In-vitro results indicated that FF-allograft and FD-allograft showed excellent biocompatibility and biomechanics, while FD-allograft showed a denser collagen fiber arrangement than FF-allograft and autograft. Then, in-vivo preformation of the FF-allograft, FD-allograft, and autograft on bone tunnel integration was evaluated via a canine ACL reconstruction model. In-vivo results indicated that no signs of infection or osteoarthritis were shown in the femur-graft-tibia complexes, but more vascularity and synovitis formed around the implanted FF-allograft. Micro-computed tomography showed that peri-graft bone in the FF-allograft group was significantly increased and remodeled compared with the FD-allograft group; Histologically, the FF-allograft group exhibited similar graft-bone tunnel healing to the FD-allograft group. Tartrate-resistant acid phosphatase (TRAP) staining showed significantly more osteoclasts presented in the FD-allograft group compared to the FF-allograft group. Meanwhile, a significantly higher failure load was shown in the FF-allograft group when compared with the FD-allograft group (P < 0.05). In conclusion, the FF-allograft integrated more firmly into the bone tunnel than the FD-allograft when used in ACL reconstruction.
10.1186/s13018-024-05191-z
Anterior cruciate ligament reconstruction in a translational model in sheep using biointegrative mineral fiber reinforced screws.
Scientific reports
Anterior cruciate ligament reconstruction (ACLR) is one of the more common procedures performed worldwide and perhaps the most widely studied construct in orthopedic literature. Interference screws are reliable and frequently used for ligament reconstruction, providing rigid fixation and facilitates graft incorporation allowing for the physiologic loads of early rehabilitation. The purpose of this study was to determine the bio-integration profile and quality of soft tissue graft when using mineral fiber-reinforced screws in an ACLR interference model. Nine sheep underwent ACLR using harvested autologous tendon graft fixated with 4.75 mm screws made of continuous mineral fibers. Histopathology and imaging evaluation at 28, 52, 104, 132-weeks (W) demonstrated mesenchymal tissue ingrowth into implant wall at 28 W, which increased at 52 W and peaked at 104 W. At 132 W, implants fully replaced by newly remodeled bone. Graft cellularity was evident at 28 W and continued to increase through 132 W as the tendon ossified at sites of bone contact. Pro-healing M2-macrophages and giant cells remained infrequent, with minor increases between 52 W and 104 W, attributed to expected phagocytic response. Pro-inflammatory cells (i.e., M1-macrophages, polymorphonuclears) were absent through the entire study course. In conclusion, bio-integrative screws provide secure soft tissue fixation with replacement by bone demonstrating graft cellularization over time.
10.1038/s41598-024-75914-z
Injectable FHE+BP composites hydrogel with enhanced regenerative capacity of tendon-bone interface for anterior cruciate ligament reconstruction.
Frontiers in bioengineering and biotechnology
Features of black phosphorous (BP) nano sheets such as enhancing mineralization and reducing cytotoxicity in bone regeneration field have been reported. Thermo-responsive FHE hydrogel (mainly composed of oxidized hyaluronic acid (OHA), poly-ε-L-lysine (ε-EPL) and F127) also showed a desired outcome in skin regeneration due to its stability and antibacterial benefits. This study investigated the application of BP-FHE hydrogel in anterior cruciate ligament reconstruction (ACLR) both in and , and addressed its effects on tendon and bone healing. This BP-FHE hydrogel is expected to bring the benefits of both components (thermo-sensitivity, induced osteogenesis and easy delivery) to optimize the clinical application of ACLR and enhance the recovery. Our results confirmed the potential role of BP-FHE significantly increased rBMSC attachment, proliferation and osteogenic differentiation with ARS and PCR analysis. Moreover, results indicated that BP-FHE hydrogels can successfully optimize the recovery of ACLR through enhancing osteogenesis and improving the integration of tendon and bone interface. Further results of Biomechanical testing and Micro-CT analysis [bone tunnel area (mm2) and bone volume/total volume (%)] demonstrated that BP can indeed accelerate bone ingrowth. Additionally, histological staining (H&E, Masson and Safranin O/fast green) and immunohistochemical analysis (COL I, COL III and BMP-2) strongly supported the ability of BP to promote tendon-bone healing after ACLR in murine animal models.
10.3389/fbioe.2023.1117090
Cartilage fragments combined with BMSCs-Derived exosomes can promote tendon-bone healing after ACL reconstruction.
Materials today. Bio
Anterior cruciate ligament reconstruction (ACLR) often fails due to the inability of tendon-bone integration to regenerate normal tissues and formation of fibrous scar tissues in the tendon-bone interface. Cartilage fragments and exosomes derived from bone mesenchymal stromal cells (BMSCs-Exos) can enhance enthesis healing. Nevertheless, the effects on the tendon-bone healing of ACLR remain unknown. This study found that BMSCs-Exos can promote the proliferation of chondrocytes in cartilage fragments, and activated the expression of chondro-related genes SOX9 and Aggrecan. The optimal effect concentration was 10 events/uL. Besides, BMSCs-Exos could significantly upregulated the expression of BMP7 and Smad5 in cartilage fragments, and further enhanced the expression of chondrogenic genes. Moreover, this study established a rat model of ACLR and implanted the BMSCs-Exos/cartilage fragment complex into the femoral bone tunnel. Results demonstrated that the mean diameters of the femoral bone tunnels were significantly smaller in the BE-CF group than those in the CF group (p = 0.038) and control group (p = 0.007) at 8 weeks after surgery. Besides, more new bone formation was observed in the femoral tunnels in the BE-CF group, as demonstrated by a larger BV/TV ratio based on the reconstructed CT scans. Histological results also revealed the regeneration of tendon-bone structures, especially fibrocartilage. Thus, these findings provide a promising result that BMSCs-Exos/cartilage fragment complex can prevent the enlargement of bone tunnel and promote tendon-bone healing after ACLR, which may have resulted from the regulation of the BMP7/Smad5 signaling axis.
10.1016/j.mtbio.2023.100819
Anterior Cruciate Ligament Reconstruction using Bone-Tendon-Bone Allograft: Surgical Technique Using Augmentation with Bio-Composite Scaffold.
Arthroscopy techniques
Anterior cruciate ligament (ACL) rupture rates remain high; the incidence of isolated ACL ruptures is 68.6 per 100,000. This Technical Note introduces a technique for ACL reconstruction (ACLR) using a bone-tendon-bone (BTB) allograft augmented with BioBrace, a biocomposite scaffold. The BioBrace scaffold is sutured onto the BTB allograft to reinforce the ligament and accelerate healing. Graft preparation with BioBrace, ACLR, and graft passage is described. This technique aims to reduce re-rupture risk, enhance graft healing, and improve patient-reported outcomes. BioBrace offers advantages over other augmentation approaches and synthetic materials, providing improved remodeling, biologic integration, and increased mechanical strength. Feasibility and efficacy have been demonstrated in animal models and human applications. This technique presents a promising approach to enhance ACLR outcomes.
10.1016/j.eats.2023.11.005
Bioactive Decellularized Tendon-Derived Stem Cell Sheet for Promoting Graft Healing After Anterior Cruciate Ligament Reconstruction.
The American journal of sports medicine
BACKGROUND:Stem cell sheets provide a scaffold-free option for the promotion of graft healing after anterior cruciate ligament reconstruction (ACLR). However, cell viability, stability, and potential uncontrolled actions create challenges for clinical translation. The decellularization of cell sheets may overcome these problems as studies have shown that the natural extracellular matrix of stem cells is bioactive and can promote tissue repair. HYPOTHESIS:The decellularized tendon-derived stem cell (dTDSC) sheet can promote graft healing after ACLR. STUDY DESIGN:Controlled laboratory study. METHODS:An optimized decellularization protocol was developed to decellularize the TDSC sheets. A total of 64 Sprague-Dawley rats underwent ACLR with or without the dTDSC sheet wrapping the tendon graft (n = 32/group). At 2 and 6 weeks after surgery, graft healing was assessed by micro-computed tomography, histology, and biomechanical testing. The accumulation of iNOS and CD206 cells and the expression of metalloproteinase 1 (MMP-1), MMP-13, and tissue inhibitor of metalloprotease 1 (TIMP-1) were assessed by immunohistochemistry. RESULTS:The decellularization was successful, with the removal of 98.4% nucleic acid while preserving the collagenous proteins and bioactive factors. The expression of bone morphogenetic protein 2 (BMP-2) and VEGF in the dTDSC sheet was comparable with the TDSC sheet ( > .05). Micro-computed tomography showed significantly more tunnel bone formation in the dTDSC sheet group. The dTDSC sheet group demonstrated better graft osteointegration and higher integrity of graft midsubstance with significantly higher ultimate failure load (16.58 ± 7.24 vs 8.93 ± 2.45 N; = .002) and stiffness (11.97 ± 5.21 vs 6.73 ± 2.20 N/mm; = .027). Significantly fewer iNOS cells but more CD206 cells, as well as lower MMP-1 and MMP-13 but higher TIMP-1 expression, were detected at the tendon-bone interface and graft midsubstance in the dTDSC sheet group. CONCLUSION:An optimized decellularization protocol for producing bioactive dTDSC sheets was developed. Wrapping tendon graft with a dTDSC sheet promoted graft healing after ACLR, likely via enhancing bone formation and angiogenesis by BMP-2 and VEGF, modulating macrophage polarization and MMP/TIMP expression, and physically protecting the tendon graft. CLINICAL RELEVANCE:dTDSC sheets alleviate the quality control and safety concerns of cell transplantation and can be used as a cell-free alternative for the promotion of graft healing in ACLR.
10.1177/03635465221135770
Mesenchymal stem cells and macrophages and their interactions in tendon-bone healing.
Journal of orthopaedic translation
Tendon-bone insertion injuries (TBI), such as anterior cruciate ligament (ACL) and rotator cuff injuries, are common degenerative or traumatic pathologies with a negative impact on the patient's daily life, and they cause huge economic losses every year. The healing process after an injury is complex and is dependent on the surrounding environment. Macrophages accumulate during the entire process of tendon and bone healing and their phenotypes progressively transform as they regenerate. As the "sensor and switch of the immune system", mesenchymal stem cells (MSCs) respond to the inflammatory environment and exert immunomodulatory effects during the tendon-bone healing process. When exposed to appropriate stimuli, they can differentiate into different tissues, including chondrocytes, osteocytes, and epithelial cells, promoting reconstruction of the complex transitional structure of the enthesis. It is well known that MSCs and macrophages communicate with each other during tissue repair. In this review, we discuss the roles of macrophages and MSCs in TBI injury and healing. Reciprocal interactions between MSCs and macrophages and some biological processes utilizing their mutual relations in tendon-bone healing are also described. Additionally, we discuss the limitations in our understanding of tendon-bone healing and propose feasible ways to exploit MSC-macrophage interplay to develop an effective therapeutic strategy for TBI injuries. The Translational potential of this article:This paper reviewed the important functions of macrophages and mesenchymal stem cells in tendon-bone healing and described the reciprocal interactions between them during the healing process. By managing macrophage phenotypes, mesenchymal stem cells and the interactions between them, some possible novel therapies for tendon-bone injury may be proposed to promote tendon-bone healing after restoration surgery.
10.1016/j.jot.2022.12.005
Strategies for promoting tendon-bone healing: Current status and prospects.
Frontiers in bioengineering and biotechnology
Tendon-bone insertion (TBI) injuries are common, primarily involving the rotator cuff (RC) and anterior cruciate ligament (ACL). At present, repair surgery and reconstructive surgery are the main treatments, and the main factor determining the curative effect of surgery is postoperative tendon-bone healing, which requires the stable combination of the transplanted tendon and the bone tunnel to ensure the stability of the joint. Fibrocartilage and bone formation are the main physiological processes in the bone marrow tract. Therefore, therapeutic measures conducive to these processes are likely to be applied clinically to promote tendon-bone healing. In recent years, biomaterials and compounds, stem cells, cell factors, platelet-rich plasma, exosomes, physical therapy, and other technologies have been widely used in the study of promoting tendon-bone healing. This review provides a comprehensive summary of strategies used to promote tendon-bone healing and analyses relevant preclinical and clinical studies. The potential application value of these strategies in promoting tendon-bone healing was also discussed.
10.3389/fbioe.2023.1118468
Strategies to promote tendon-bone healing after anterior cruciate ligament reconstruction: Present and future.
Frontiers in bioengineering and biotechnology
At present, anterior cruciate ligament (ACL) reconstruction still has a high failure rate. Tendon graft and bone tunnel surface angiogenesis and bony ingrowth are the main physiological processes of tendon-bone healing, and also the main reasons for the postoperative efficacy of ACL reconstruction. Poor tendon-bone healing has been also identified as one of the main causes of unsatisfactory treatment outcomes. The physiological process of tendon-bone healing is complicated because the tendon-bone junction requires the organic fusion of the tendon graft with the bone tissue. The failure of the operation is often caused by tendon dislocation or scar healing. Therefore, it is important to study the possible risk factors for tendon-bone healing and strategies to promote it. This review comprehensively analyzed the risk factors contributing to tendon-bone healing failure after ACL reconstruction. Additionally, we discuss the current strategies used to promote tendon-bone healing following ACL reconstruction.
10.3389/fbioe.2023.1104214
Therapeutic potential and mechanisms of mesenchymal stem cell-derived exosomes as bioactive materials in tendon-bone healing.
Journal of nanobiotechnology
Tendon-bone insertion (TBI) injuries, such as anterior cruciate ligament injury and rotator cuff injury, are the most common soft tissue injuries. In most situations, surgical tendon/ligament reconstruction is necessary for treating such injuries. However, a significant number of cases failed because healing of the enthesis occurs through scar tissue formation rather than the regeneration of transitional tissue. In recent years, the therapeutic potential of mesenchymal stem cells (MSCs) has been well documented in animal and clinical studies, such as chronic paraplegia, non-ischemic heart failure, and osteoarthritis of the knee. MSCs are multipotent stem cells, which have self-renewability and the ability to differentiate into a wide variety of cells such as chondrocytes, osteoblasts, and adipocytes. Numerous studies have suggested that MSCs could promote angiogenesis and cell proliferation, reduce inflammation, and produce a large number of bioactive molecules involved in the repair. These effects are likely mediated by the paracrine mechanisms of MSCs, particularly through the release of exosomes. Exosomes, nano-sized extracellular vesicles (EVs) with a lipid bilayer and a membrane structure, are naturally released by various cell types. They play an essential role in intercellular communication by transferring bioactive lipids, proteins, and nucleic acids, such as mRNAs and miRNAs, between cells to influence the physiological and pathological processes of recipient cells. Exosomes have been shown to facilitate tissue repair and regeneration. Herein, we discuss the prospective applications of MSC-derived exosomes in TBI injuries. We also review the roles of MSC-EVs and the underlying mechanisms of their effects on promoting tendon-bone healing. At last, we discuss the present challenges and future research directions.
10.1186/s12951-023-01778-6
Challenges in tendon-bone healing: emphasizing inflammatory modulation mechanisms and treatment.
Frontiers in endocrinology
Tendons are fibrous connective tissues that transmit force from muscles to bones. Despite their ability to withstand various loads, tendons are susceptible to significant damage. The healing process of tendons and ligaments connected to bone surfaces after injury presents a clinical challenge due to the intricate structure, composition, cellular populations, and mechanics of the interface. Inflammation plays a pivotal role in tendon healing, creating an inflammatory microenvironment through cytokines and immune cells that aid in debris clearance, tendon cell proliferation, and collagen fiber formation. However, uncontrolled inflammation can lead to tissue damage, and adhesions, and impede proper tendon healing, culminating in scar tissue formation. Therefore, precise regulation of inflammation is crucial. This review offers insights into the impact of inflammation on tendon-bone healing and its underlying mechanisms. Understanding the inflammatory microenvironment, cellular interactions, and extracellular matrix dynamics is essential for promoting optimal healing of tendon-bone injuries. The roles of fibroblasts, inflammatory cytokines, chemokines, and growth factors in promoting healing, inhibiting scar formation, and facilitating tissue regeneration are discussed, highlighting the necessity of balancing the suppression of detrimental inflammatory responses with the promotion of beneficial aspects to enhance tendon healing outcomes. Additionally, the review explores the significant implications and translational potential of targeted inflammatory modulation therapies in refining strategies for tendon-bone healing treatments.
10.3389/fendo.2024.1485876
Bone marrow mesenchymal stem cell‑derived exosomes: A novel therapeutic agent for tendon‑bone healing (Review).
International journal of molecular medicine
In sports medicine, injuries related to the insertion of tendons into bones, including rotator cuff injuries, anterior cruciate ligament injuries and Achilles tendon ruptures, are commonly observed. However, traditional therapies have proven to be insufficient in achieving satisfactory outcomes due to the intricate anatomical structure associated with these injuries. Adult bone marrow mesenchymal stem cells possess self‑renewal and multi‑directional differentiation potential and can generate various mesenchymal tissues to aid in the recovery of bone, cartilage, adipose tissue and bone marrow hematopoietic tissue. In addition, extracellular vesicles derived from bone marrow mesenchymal stem cells known as exosomes, contain lipids, proteins and nucleic acids that govern the tissue microenvironment, facilitate tissue repair and perform various biological functions. Studies have demonstrated that bone marrow mesenchymal stem cell‑derived exosomes can function as natural nanocapsules for drug delivery and can enhance tendon‑bone healing strength. The present review discusses the latest research results on the role of exosomes released by bone marrow mesenchymal stem cells in tendon‑bone healing and provides valuable information for implementing these techniques in regenerative medicine and sports health.
10.3892/ijmm.2023.5324
Engineered exosomes: a promising strategy for tendon-bone healing.
Journal of advanced research
BACKGROUND:Due to the spatiotemporal complexity of the composition, structure, and cell population of the tendon-bone interface (TBI), it is difficult to achieve true healing. Recent research is increasingly focusing on engineered exosomes, which are a promising strategy for TBI regeneration. AIM OF REVIEW:This review discusses the physiological and pathological characteristics of TBI and the application and limitations of natural exosomes in the field of tendon-bone healing. The definition, loading strategies, and spatiotemporal properties of engineered exosomes were elaborated. We also summarize the application and future research directions of engineered exosomes in the field of tendon-bone healing. KEY SCIENTIFIC CONCEPTS OF REVIEW:Engineered exosomes can spatially deliver cargo to targeted sites and temporally realize the sustained release of therapeutic molecules in TBI. This review expounds on the multidifferentiation of engineered exosomes for tendon-bone healing, which effectively improves the biological and biomechanical properties of TBI. Engineered exosomes could be a promising strategy for tendon-bone healing.
10.1016/j.jare.2023.11.011
Synergistic enhancement of tendon-to-bone healing via anti-inflammatory and pro-differentiation effects caused by sustained release of Mg/curcumin from injectable self-healing hydrogels.
Chen Baojun,Liang Yongping,Zhang Jing,Bai Lang,Xu Meiguang,Han Qian,Han Xuezhe,Xiu Jintao,Li Meng,Zhou Xiaoling,Guo Baolin,Yin Zhanhai
Theranostics
Poor healing response after rotator cuff reconstruction is multifactorial, with the inflammatory microenvironment and deficiency of stem cell differentiation factors at the lesion site being most relevant. However, there is a lack of effective tissue engineering strategies that can simultaneously exert anti-inflammatory and pro-differentiation effects to promote rotator cuff healing. In this study, we synthesized and characterized a novel active drug delivery vector that successfully overcame the challenge of simultaneous high-efficiency loading and controlled release of Mg and curcumin. The anti-inflammatory and pro-differentiation effects of the composite hydrogel were evaluated and . Moreover, healing of the rotator cuff tendon-to-bone interface was studied by histology, immunofluorescence, and biomechanical tests. The composite hydrogel exhibited excellent biocompatibility and injectability, good adhesiveness, and rapid self-healing. The released curcumin showed obvious anti-inflammatory and antioxidation effects, which protected stem cells and tendon matrix. Furthermore, released Mg promoted stem cell aggregation and chondrogenesis. Moreover, biomechanical tests and histological results of a rat rotator cuff tear model at 8 weeks after surgery indicated that the composite hydrogel significantly enhanced tendon-to-bone healing. The composite hydrogel mediated sustained release of curcumin and Mg to effectively promote rotator cuff tendon-to-bone healing via anti-inflammatory and pro-differentiation effects. Therefore, this composite hydrogel offers significant promise for rotator cuff repair.
10.7150/thno.56266