Comparison of Cellular Responses to TGF-β1 and BMP-2 Between Healthy and Torn Tendons.
The American journal of sports medicine
BACKGROUND:Tendons heal by fibrotic repair, increasing the likelihood of reinjury. Animal tendon injury and overuse models have identified transforming growth factor beta (TGF-β) and bone morphogenetic proteins (BMPs) as growth factors actively involved in the development of fibrosis, by mediating extracellular matrix synthesis and cell differentiation. PURPOSE:To understand how TGF-β and BMPs contribute to fibrotic processes using tendon-derived cells isolated from healthy and diseased human tendons. STUDY DESIGN:Controlled laboratory study. METHODS:Tendon-derived cells were isolated from patients with a chronic rotator cuff tendon tear (large to massive, diseased) and healthy hamstring tendons of patients undergoing anterior cruciate ligament repair. Isolated cells were incubated with TGF-β1 (10 ng/mL) or BMP-2 (100 ng/mL) for 3 days. Gene expression was measured by real-time quantitative polymerase chain reaction. Cell signaling pathway activation was determined by Western blotting. RESULTS:TGF-β1 treatment induced mRNA expression in both cell types but less in the diseased compared with healthy cells ( < .05). BMP-2 treatment induced mRNA expression in healthy but not diseased cells ( < .01). In the diseased cells, TGF-β1 treatment induced increased mRNA expression ( < .01) and increased small mothers against decapentaplegic (SMAD) signaling ( < .05) compared with those of healthy cells. Moreover, BMP-2 treatment induced mRNA expression in the diseased cells only ( < .05). CONCLUSION:Diseased tendon-derived cells show reduced expression of the proteoglycans aggrecan and biglycan in response to TGF-β1 and BMP-2 treatments. These same treatments induced enhanced fibrotic differentiation and canonical SMAD cell signaling in diseased compared with healthy cells. CLINICAL RELEVANCE:Findings from this study suggest that diseased tendon-derived cells respond differently than healthy cells in the presence of TGF-β1 and BMP-2. The altered responses of diseased cells may influence fibrotic repair processes during tendon healing.
10.1177/03635465211011158
Tendon-derived extracellular matrix induces mesenchymal stem cell tenogenesis via an integrin/transforming growth factor-β crosstalk-mediated mechanism.
Wang Dan,Pun Charmaine C M,Huang Shuting,Tang Thomas C M,Ho Kevin K W,Rothrauff Benjamin B,Yung Patrick S H,Blocki Anna M,Ker Elmer D F,Tuan Rocky S
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Treatment of tendon injuries is challenging. To develop means to augment tendon regeneration, we have previously prepared a soluble, low immunogenic (DNA-free), tendon extracellular matrix fraction (tECM) by urea extraction of juvenile bovine tendons, which is capable of enhancing transforming growth factor-β (TGF-β) mediated tenogenesis in human adipose-derived stem cells (hASCs). Here, we aimed to elucidate the mechanism of tECM-driven hASC tenogenic differentiation in vitro, focusing on the integrin and TGF-β/SMAD pathways. Our results showed that tECM promoted hASC proliferation and tenogenic differentiation in vitro based on tenogenesis-associated markers. tECM also induced higher expression of several integrin subunits and TGF-β receptors, and nuclear translocation of p-SMAD2 in hASCs. Pharmacological inhibition of integrin-ECM binding, focal adhesion kinase (FAK) signaling, or TGF-β signaling independently led to compromised pro-tenogenic effects of tECM and actin fiber polymerization. Additionally, integrin blockade inhibited tECM-driven TGFBR2 expression, while inhibiting TGF-β signaling decreased tECM-mediated expression of integrin α1, α2, and β1 in hASCs. Together, these findings suggest that the strong pro-tenogenic bioactivity of tECM is regulated via integrin/TGF-β signaling crosstalk. Understanding how integrins interact with signaling by TGF-β and/or other growth factors (GFs) within the tendon ECM microenvironment will provide a rational basis for an ECM-based approach for tendon repair.
10.1096/fj.201902377RR
[Outcomes of quadriceps tendon autograft versus bone-patellar tendon-bone autograft for anterior cruciate ligament reconstruction:a Meta-analysis].
Li Fei,Gu Xiao-Dong,Wei Xiao-Chun
Zhongguo gu shang = China journal of orthopaedics and traumatology
OBJECTIVE:To evaluate clinical effect of quadriceps tendon autograft and bone-patellar tendon-bone autograft on anterior cruciate ligament reconstruction by Meta-analysis. METHODS:From the time of building databases to May 2019, literatures on case control study on quadriceps tendon and bone-patellar tendon-bone autograft on anterior cruciate ligament reconstruction were searched form PubMed, EMbase, the Cochrane library, Wanfang and CNKI database. Literature screening, quality evaluation and data extraction were carried out according to include and exclude standard. Difference of forward displacement between the affected and health knee, Lachman test, axial shift test, Lysholm score, international knee documentation committee (IKDC) objective grade, anterior knee joint pain and transplant failure rate were analyzed by Meta analysis. RESULTS:Totally 6 literatures were included, including 915 patients with anterior cruciate ligament reconstruction, 495 patients with quadriceps tendon autograft and 420 patients with bone patellar tendon bone autograft. There were no statistical differences in anterior displacement of tibia was less than 3 mm[=1.53, 95%CI(0.68, 3.44), =0.31], 3 to 5 mm [=0.64, 95%CI(0.31, 1.35), =0.24], greater than 5 mm[=1.18, 95%CI(0.33, 4.22), =0.80], negative rate of Lachman test[=0.88, 95%CI(0.38, 2.02), =0.76], negative rate of axial shift test[=0.63, 95%CI(0.24, 1.68), =0.36] between two groups. There were no differences in Lyshlom score[=-0.56, 95%CI(-2.00, 0.89), =0.45], IKDC objective grade A and B[=0.87, 95%CI (0.47, 1.60), =0.66], and transplant failure rate [=0.76, 95%CI (0.28, 2.02), = 0.58]. In reducing anterior knee pain, quadriceps tendon autograft was better than that of bone patellar tendon bone autograft [=0.16, 95%CI (0.09, 0.29), <0.000 01]. CONCLUSION:Quadriceps tendon autograft and bone patellar tendon bone autograft on anterior cruciate ligament reconstruction has equal clinical and functional outcomes, transplant failure rate, quadriceps tendon autograft could reduce anterior knee pain. For patients with anterior cruciate ligament reconstruction, quadriceps tendon autograft could be seen as suitable alternative bone graft substitutes for anterior cruciate ligament reconstruction.
10.12200/j.issn.1003-0034.2020.07.018
Citrate-based mussel-inspired magnesium whitlockite composite adhesives augmented bone-to-tendon healing.
Yuan Xiaowei,Zhao Yitao,Li Jintao,Chen Xuncai,Lu Zhihui,Li Lianyong,Guo Jinshan
Journal of materials chemistry. B
Citrate-based mussel-inspired whitlockite composite adhesives (CMWAs) were developed and administered to the bone-tendon interface in anterior cruciate ligament (ACL) reconstruction. CMWAs could improve the initial bone-tendon bonding strength, promote the bony inward growth from the bone tunnel and enhance the chondrogenesis and osteogenesis of the bone-tendon interface, thus augmenting bone-to-tendon healing.
10.1039/d1tb01710a
Mesenchymal stromal cells and platelet-rich plasma promote tendon allograft healing in ovine anterior cruciate ligament reconstruction.
Hexter Adam T,Sanghani-Kerai Anita,Heidari Nima,Kalaskar Deepak M,Boyd Ashleigh,Pendegrass Catherine,Rodeo Scott A,Haddad Fares S,Blunn Gordon W
Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA
PURPOSE:The effect of bone marrow mesenchymal stromal cells (BMSCs) and platelet-rich plasma (PRP) on tendon allograft maturation in a large animal anterior cruciate ligament (ACL) reconstruction model was reported for the first time. It was hypothesised that compared with non-augmented ACL reconstruction, BMSCs and PRP would enhance graft maturation after 12 weeks and this would be detected using magnetic resonance imaging (MRI). METHODS:Fifteen sheep underwent unilateral tendon allograft ACL reconstruction using aperture fixation and were randomised into three groups (n = 5). Group 1 received 10 million allogeneic BMSCs in 2 ml fibrin sealant; Group 2 received 12 ml PRP in a plasma clot injected into the graft and bone tunnels; and Group 3 (control) received no adjunctive treatment. At autopsy at 12 weeks, a graft maturation score was determined by the sum for graft integrity, synovial coverage and vascularisation, graft thickness and apparent tension, and synovial sealing at tunnel apertures. MRI analysis (n = 2 animals per group) of the signal-noise quotient (SNQ) and fibrous interzone (FIZ) was used to evaluate intra-articular graft maturation and tendon-bone healing, respectively. Spearman's rank correlation coefficient (r) of SNQ, autopsy graft maturation score and bone tunnel diameter were analysed. RESULTS:The BMSC group (p = 0.01) and PRP group (p = 0.03) had a significantly higher graft maturation score compared with the control group. The BMSC group scored significantly higher for synovial sealing at tunnel apertures (p = 0.03) compared with the control group. The graft maturation score at autopsy significantly correlated with the SNQ (r = - 0.83, p < 0.01). The tunnel diameter of the femoral tunnel at the aperture (r = 0.883, p = 0.03) and mid-portion (r = 0.941, p = 0.02) positively correlated with the SNQ. CONCLUSIONS:BMSCs and PRP significantly enhanced graft maturation, which indicates that orthobiologics can accelerate the biologic events in tendon allograft incorporation. Femoral tunnel expansion significantly correlated with inferior maturation of the intra-articular graft. The clinical relevance of this study is that BMSCs and PRP enhance allograft healing in a translational model, and biological modulation of graft healing can be evaluated non-invasively using MRI.
10.1007/s00167-020-06392-9
Tissue-Engineered Decellularized Allografts for Anterior Cruciate Ligament Reconstruction.
Li Yamin,Zhu Tonghe,Wang Liren,Jiang Jia,Xie Guoming,Huangfu Xiaoqiao,Dong Shikui,Zhao Jinzhong
ACS biomaterials science & engineering
Anterior cruciate ligament (ACL) reconstruction with allografts is limited by high immunogenicity, poor cellularization, and delayed tendon-bone healing. Decellularized tendons (DAs) have been used as bioscaffolds to reconstruct ligaments with variable success. In the study, four kinds of decellularized allogeneic hamstring tendons were prepared and their microstructure and cytocompatibility were examined in vitro. The results showed that decellularized allografts neutralized by 5% calcium bicarbonate had typical reticular and porous microstructures with optical cytocompatibility. Tissue-engineering decellularized allografts (TEDAs) were prepared with the selected decellularized allografts and tendon stem/progenitor cells and used for ACL reconstruction in a rabbit model. Histological staining showed that the TEDAs promoted cellular infiltration and new vessel formation significantly and improved tendon-bone healing moderately compared to decellularized allografts. Better macroscopic scores and biomechanical results were observed in TEDA groups, but there were no significant differences between DA and TEDA groups at months 1, 2, and 3 postoperatively. Immunohistochemical data showed that the tissue-engineering decellularized allografts enhanced the expression of collagen I at each timepoint and collagen III at months 1 and 2. ELISA analysis showed that the tissue-engineering decellularized allografts reduced the secretion of IgE and IL-1β within 1 month and promoted the secretion of IL-2, IL-4, IL-10, and IL-17 after 1 month. The results showed that tissue-engineering decellularized allografts strengthened intra-articular graft remodeling significantly and provided moderate improvements in tendon-bone healing by creating more suitable immune responses than decellularized allografts. The study revealed that tissue-engineering decellularized allografts as a promising option for ACL reconstruction could achieve more favorable outcomes.
10.1021/acsbiomaterials.0c00269
Bioresorbable Stent in Anterior Cruciate Ligament Reconstruction.
Ficek Krzysztof,Rajca Jolanta,Stolarz Mateusz,Stodolak-Zych Ewa,Wieczorek Jarosław,Muzalewska Małgorzata,Wyleżoł Marek,Wróbel Zygmunt,Binkowski Marcin,Błażewicz Stanisław
Polymers
The exact causes of failure of anterior cruciate ligament (ACL) reconstruction are still unknown. A key to successful ACL reconstruction is the prevention of bone tunnel enlargement (BTE). In this study, a new strategy to improve the outcome of ACL reconstruction was analyzed using a bioresorbable polylactide (PLA) stent as a catalyst for the healing process. The study included 24 sheep with 12 months of age. The animals were randomized to the PLA group (n = 16) and control group (n = 8), subjected to the ACL reconstruction with and without the implantation of the PLA tube, respectively. The sheep were sacrificed 6 or 12 weeks post-procedure, and their knee joints were evaluated by X-ray microcomputed tomography with a 50 μm resolution. While the analysis of tibial and femoral tunnel diameters and volumes demonstrated the presence of BTE in both groups, the enlargement was less evident in the PLA group. Also, the microstructural parameters of the bone adjacent to the tunnels tended to be better in the PLA group. This suggested that the implantation of a bioresorbable PLA tube might facilitate osteointegration of the tendon graft after the ACL reconstruction. The beneficial effects of the stent were likely associated with osteogenic and osteoconductive properties of polylactide.
10.3390/polym11121961
Effect of Freshly Isolated Bone Marrow Mononuclear Cells and Cultured Bone Marrow Stromal Cells in Graft Cell Repopulation and Tendon-Bone Healing after Allograft Anterior Cruciate Ligament Reconstruction.
Lu Cheng-Chang,Ho Cheng-Jung,Huang Hsuan-Ti,Lin Sung-Yen,Chou Shih-Hsiang,Chou Pei-Hsi,Ho Mei-Ling,Tien Yin-Chun
International journal of molecular sciences
Graft cell repopulation and tendon-bone tunnel healing are important after allograft anterior cruciate ligament reconstruction (ACLR). Freshly isolated bone marrow mononuclear cells (BMMNCs) have the advantage of short isolation time during surgery and may enhance tissue regeneration. Thus, we hypothesized that the effect of intra-articular BMMNCs in post-allograft ACLR treatment is comparable to that of cultured bone marrow stromal cells (BMSCs). A rabbit model of hamstring allograft ACLR was used in this study. Animals were randomly assigned to the BMMNC, BMSC, and control groups. Fresh BMMNCs isolated from the iliac crest during surgery and cultured BMSCs at passage four were used in this study. A total of 1 × 10 BMMNCs or BMSCs in 100 µL phosphate-buffered saline were injected into the knee joint immediately after ACLR. The control group was not injected with cells. At two and six weeks post operation, we assessed graft cell repopulation with histological and cell tracking staining (PKH26), and tendon-bone healing with histological micro-computed tomography and immunohistochemical analyses for collagen I and monocyte chemoattractant protein-1 (MCP1). At two weeks post operation, there was no significant difference in the total cell population within the allograft among the three groups. However, the control group showed significantly higher cell population within the allograft than that of BM cell groups at six weeks. Histological examination of proximal tibia revealed that the intra-articular delivered cells infiltrated into the tendon-bone interface. Compared to the control group, the BM cell groups showed broader gaps with interfacial fibrocartilage healing, similar collagen I level, and higher MCP1 expression in the early stage. Micro-CT did not reveal any significant difference among the three groups. BMMNCs and BMSCs had comparable effects on cell repopulation and interfacial allograft-bone healing. Intra-articular BM cells delivery had limited benefits on graft cell repopulation and caused higher inflammation than that in the control group in the early stage, with fibrocartilage formation in the tendon-bone interface after allograft ACLR.
10.3390/ijms22062791
Femoral Interference Screw Fixation in ACL Reconstruction Using Bone-Patellar Tendon-Bone Grafts.
Su Charles A,Knapik Derrick M,Trivedi Nikunj N,Megerian Mark F,Salata Michael J,Voos James E
JBJS reviews
» Anterior cruciate ligament (ACL) reconstruction is a commonly performed orthopaedic procedure with numerous reconstructive graft and fixation options. Interference screws have become one of the most commonly utilized methods of securing ACL grafts such as bone-patellar tendon-bone (BPTB) autografts.» The composition of interference screws has undergone substantial evolution over the past several decades, and numerous advantages and disadvantages are associated with each design.» The composition, geometry, and insertional torque of interference screws have important implications for screw biomechanics and may ultimately influence the strength, stability of graft fixation, and biologic healing in ACL reconstruction.» This article reviews the development and biomechanical properties of interference screws while examining outcomes, complications, and gaps in knowledge that are associated with the use of femoral interference screws during BPTB ACL reconstruction.
10.2106/JBJS.RVW.19.00066
Magnesium-pretreated periosteum for promoting bone-tendon healing after anterior cruciate ligament reconstruction.
Wang Jiali,Xu Jiankun,Wang Xinluan,Sheng Liyuan,Zheng Lizhen,Song Bin,Wu Ge,Zhang Ri,Yao Hao,Zheng Nianye,Yun Ong Michael Tim,Yung Patrick Shu-Hang,Qin Ling
Biomaterials
Periosteum can improve tendon-bone healing when applied to wrap the tendon graft in both animal studies and clinical trials. As magnesium (Mg) ions can significantly elevate the levels of relevant cytokines involving in the osteogenic differentiation of periosteum-derived stem cells, the Mg-pretreated periosteum may be an innovative approach for enveloping the tendon graft. To test this hypothesis, we compared the effects of Mg-pretreated periosteum (M - P) and the stainless steel (SS)-pretreated periosteum (SS-P) in ACL reconstruction. We firstly found that the released Mg ions from the Mg implants were partially accumulated in periosteum, resulting in higher Mg/Ca ratio in the M - P compared to the SS-P. Additionally, the M - P showed significantly higher expression levels of calcitonin gene-related peptide (CGRP) and periostin than the SS-P due to the decrease in Cathepsin K (CTSK). Elevation of CGRP and periostin was beneficial for the osteogenic differentiation of periosteum-derived stem cells. More importantly, we demonstrated that the M - P remarkably increased the formation of fibrocartilage at the interface between the periosteum and tendon. Collectively, M - P group demonstrated significantly prevented peri-tunnel bone loss, more osseous ingrowth into the tendon graft and higher maximum load to failure as compared to the SS-P group. In summary, our study warrants further investigations for translating the current proof-of-concept findings to optimize the delivery of CGRP, periostin, and cells as novel practical therapeutic strategy for enhancing tendon-bone interface healing in patients undergoing ACL reconstruction.
10.1016/j.biomaterials.2020.120576
Stem cell therapies in tendon-bone healing.
Xu Yue,Zhang Wan-Xia,Wang Li-Na,Ming Yue-Qing,Li Yu-Lin,Ni Guo-Xin
World journal of stem cells
Tendon-bone insertion injuries such as rotator cuff and anterior cruciate ligament injuries are currently highly common and severe. The key method of treating this kind of injury is the reconstruction operation. The success of this reconstructive process depends on the ability of the graft to incorporate into the bone. Recently, there has been substantial discussion about how to enhance the integration of tendon and bone through biological methods. Stem cells like bone marrow mesenchymal stem cells (MSCs), tendon stem/progenitor cells, synovium-derived MSCs, adipose-derived stem cells, or periosteum-derived periosteal stem cells can self-regenerate and potentially differentiate into different cell types, which have been widely used in tissue repair and regeneration. Thus, we concentrate in this review on the current circumstances of tendon-bone healing using stem cell therapy.
10.4252/wjsc.v13.i7.753
Graft Selection in Anterior Cruciate Ligament Reconstruction.
Lin Kenneth M,Boyle Caroline,Marom Niv,Marx Robert G
Sports medicine and arthroscopy review
Surgical reconstruction of the anterior cruciate ligament (ACL) is often indicated to restore functional stability and prevent early degeneration of the knee joint, as there is little biological healing capacity of the native ACL. Although a reconstructed ACL does not fully restore the original structure or biomechanics properties of the native ACL, the graft used for reconstruction must not only have structural and mechanical properties that closely resemble those of the native ligament, it must also have minimal antigenicity and enough biological potential to incorporate into host bone. There are several considerations in graft selection: autograft versus allograft, and soft tissue grafts versus grafts with bone plugs. Commonly used grafts include bone-patella tendon-bone, hamstring, and quadriceps; among allografts, options further include tibias anterior and posterior, Achilles, an peroneal tendons. Optimal graft selection is not only dependent on graft properties, but perhaps more importantly on patient characteristics and expectations. The purpose of this review is to summarize the relevant biological, biomechancial, and clinical data regarding various graft types and to provide a basic framework for graft selection in ACL reconstruction.
10.1097/JSA.0000000000000265
Effects of Platelet-Rich Plasma on Tendon-Bone Healing After Anterior Cruciate Ligament Reconstruction.
Chen Rong-Jin,Zhu Hao-Zhong,Gu Xin-Yi,Xiang Xian-Xiang
Orthopaedic surgery
OBJECTIVE:To investigate the effect of platelet-rich plasma on tendon-bone healing after anterior cruciate ligament reconstruction. METHODS:This retrospective study included 85 patients (range, 18-50 years; mean age, 33.95 ± 10.53 years; male/female, 49/36) who underwent anterior cruciate ligament reconstruction using autologous hamstring tendons between August 2017 and June 2019 at our institute. The participants in the study group (n = 42) were injected with platelet-rich plasma at both ends of the tendon graft, while those in the control group (n = 43) received an injection of normal saline. Magnetic resonance imaging signal/noise quotient values of the femoral and tibial ends, knee Lysholm scores, and International Knee Documentation Committee scores were compared at 3, 6, and 12 months postoperatively. RESULTS:The signal/noise quotient values of the femoral and tibial ends in both groups were higher at 6 months than at 3 and 12 months postoperatively. The signal/noise quotient values of the tibial end were significantly lower in the platelet-rich plasma group than in the normal saline group at all follow-up time points (P < 0.05). The signal/noise quotient values of the tibial and femoral ends in both groups were significantly different at 3, 6, and 12 months postoperatively (P < 0.05). Additionally, the signal/noise quotient values of the tibia were significantly lower than those of the femur in both groups (P < 0.05). The Lysholm and International Knee Documentation Committee scores were significantly better in the platelet-rich plasma group than in the normal saline group only at 3 months postoperatively. No complications, such as knee joint infection or vascular and nerve injuries, occurred in any of the 85 patients. The knee flexion of all patients were more than 90°, and the straight degree was 0°. No joint stiffness was observed in all patients. CONCLUSION:Platelet-rich plasma can promote tendon-bone healing in grafts and can improve early postoperative knee joint function.
10.1111/os.13175
Opportunities and challenges of hydrogel microspheres for tendon-bone healing after anterior cruciate ligament reconstruction.
Zhao Xibang,Zhou Yuanyuan,Li Jianting,Zhang Chao,Wang Jiali
Journal of biomedical materials research. Part B, Applied biomaterials
Poor angiogenesis and bony ingrowth are the major factors causing unsatisfactory healing between the tendon graft and the bone tunnel surface. Exogenous biological factors, biomaterials, and cells have been considered as new strategies to promote healing quality in recent years. However, it remains challenging for their clinical use because of insufficient in-situ retention time and release efficiency. Increasing attention has been paid to the hydrogel microspheres (HMPs) as potential drug-loading deliveries in biomedicine due to their minimally invasive manner, extended drug retention time, and high loading efficiency. In this review, the healing mechanism between the tendon graft and the bone tunnel is introduced, which is followed by a brief summarization of current methods applied for enhancement of the healing quality. Then, the preclinical studies focusing on HMPs as novel drug carriers are summarized to address the aforementioned concerns in the treatment of tendon-bone healing. Of note, the challenges and perspectives of HMPs in clinical conversion are also outlooked. Collectively, this review may inspire researchers and clinicians to develop clinical available HMPs in orthopedics such as sports medicine from both material and biomedical aspects.
10.1002/jbm.b.34925
Stem cell therapy: a promising biological strategy for tendon-bone healing after anterior cruciate ligament reconstruction.
Hao Zi-Chen,Wang Shan-Zheng,Zhang Xue-Jun,Lu Jun
Cell proliferation
Tendon-bone healing after anterior cruciate ligament (ACL) reconstruction is a complex process, impacting significantly on patients' prognosis. Natural tendon-bone healing usually results in fibrous scar tissue, which is of inferior quality compared to native attachment. In addition, the early formed fibrous attachment after surgery is often not reliable to support functional rehabilitation, which may lead to graft failure or unsatisfied function of the knee joint. Thus, strategies to promote tendon-bone healing are crucial for prompt and satisfactory functional recovery. Recently, a variety of biological approaches, including active substances, gene transfer, tissue engineering and stem cells, have been proposed and applied to enhance tendon-bone healing. Among these, stem cell therapy has been shown to have promising prospects and draws increasing attention. From commonly investigated bone marrow-derived mesenchymal stem cells (bMSCs) to emerging ACL-derived CD34+ stem cells, multiple stem cell types have been proven to be effective in accelerating tendon-bone healing. This review describes the current understanding of tendon-bone healing and summarizes the current status of related stem cell therapy. Future limitations and perspectives are also discussed.
10.1111/cpr.12242
Tendon Healing in Bone Tunnel after Human Anterior Cruciate Ligament Reconstruction: A Systematic Review of Histological Results.
Lu Hongbin,Chen Can,Xie Shanshan,Tang Yifu,Qu Jin
The journal of knee surgery
Most studies concerning to tendon healing and incorporation into bone are mainly based on animal studies due to the invasive nature of the biopsy procedure. The evidence considering tendon graft healing to bone in humans is limited in several case series or case reports, and therefore, it is difficult to understand the healing process. A computerized search using relevant search terms was performed in the PubMed, EMBASE, Scopus, and Cochrane Library databases, as well as a manual search of reference lists. Searches were limited to studies that investigated tendon graft healing to bone by histologic examination after anterior cruciate ligament (ACL) reconstruction with hamstring. Ten studies were determined to be eligible for this systematic review. Thirty-seven cases were extracted from the included studies. Most studies showed that a fibrovascular interface would form at the tendon-bone interface at the early stage and a fibrous indirect interface with Sharpey-like fibers would be expected at the later stage. Cartilage-like tissue at tendon graft-bone interface was reported in three studies. Tendon graft failed to integrate with the surrounding bone in 10 of the 37 cases. Unexpectedly, suspensory type of fixation was used for the above failure cases. An indirect type of insertion with Sharpey-like fibers at tendon-bone interface could be expected after ACL reconstruction with hamstring. Regional cartilage-like tissue may form at tendon-bone interface occasionally. The underlying tendon-to-bone healing process is far from understood in the human hamstring ACL reconstruction. Further human studies are highly needed to understand tendon graft healing in bone tunnel after hamstring ACL reconstruction.
10.1055/s-0038-1653964
FGF2: a key regulator augmenting tendon-to-bone healing and cartilage repair.
Regenerative medicine
Ligament/tendon and cartilage injuries are clinically common diseases that perplex most clinicians. Because of the lack of blood vessels and nerves, their self-repairing abilities are rather poor. Therefore, surgeries are necessary and also widely used to treat ligament/tendon or cartilage injuries. However, after surgery, there are still many problems that affect healing. In recent years, it has been found that exogenous FGF2 plays an important role in the repair of ligament/tendon and cartilage injuries and exerts a synergistic effect with endogenous FGF2. Therefore, FGF2 can be used as a new type of biomolecule to accelerate tendon-to-bone healing and cartilage repair after injury.
10.2217/rme-2019-0080