Endogenous Electric-Field-Coupled Electrospun Short Fiber via Collecting Wound Exudation.
Wang Juan,Lin Jiawei,Chen Liang,Deng Lianfu,Cui Wenguo
Advanced materials (Deerfield Beach, Fla.)
Endogenous electric fields (EF) are the basis of bioelectric signal conduction and the priority signal for damaged tissue regeneration. Tissue exudation directly affects the characteristics of endogenous EF. However, current biomaterials lead to passive repair of defect tissue due to limited management of early wound exudates and inability to actively respond to coupled endogenous EF. Herein, the 3D bionic short-fiber scaffold with the functions of early biofluid collection, response to coupled endogenous EF, is constructed by guiding the short fibers into a 3D network structure and subsequent multifunctional modification. The scaffold exhibits rapid reversible water absorption, reaching maximum after only 30 s. The stable and uniform distribution of polydopamine-reduced graphene oxide endows the scaffold with stable electrical and mechanical performances even after long-term immersion. Due to its unique - bionic structure and tissue affinity, the scaffold further acts as an "electronic skin," which transmits endogenous bioelectricity via absorbing wound exudates, promoting the treatment of diabetic wounds. Furthermore, under the endogenous EF, the cascade release of vascular endothelial growth factor accelerates the healing process. Thus, the versatile scaffold is expected to be an ideal candidate for repairing different defect tissues, especially electrosensitive tissues.
10.1002/adma.202108325
Granular Porous Nanofibrous Microspheres Enhance Cellular Infiltration for Diabetic Wound Healing.
ACS nano
Diabetic foot ulcers (DFUs) are a significant challenge in the clinical care of diabetic patients, often necessitating limb amputation and compromising the quality of life and life expectancy of this cohort. Minimally invasive therapies, such as modular scaffolds, are at the forefront of current DFU treatment, offering an efficient approach for administering therapeutics that accelerate tissue repair and regeneration. In this study, we report a facile method for fabricating granular nanofibrous microspheres (NMs) with predesigned structures and porosities. The proposed technology combines electrospinning and electrospraying to develop a therapeutic option for DFUs. Specifically, porous NMs were constructed using electrospun poly(lactic--glycolic acid) (PLGA):gelatin short nanofibers, followed by gelatin cross-linking. These NMs demonstrated enhanced cell adhesion to human dermal fibroblasts (HDF) during an cytocompatibility assessment. Notably, porous NMs displayed superior performance owing to their interconnected pores compared to nonporous NMs. Cell-laden NMs demonstrated higher Young's modulus values than NMs without loaded cells, suggesting improved material resiliency attributed to the reinforcement of cells and their secreted extracellular matrix. Dynamic injection studies on cell-laden NMs further elucidated their capacity to safeguard loaded cells under pressure. In addition, porous NMs promoted host cell infiltration, neovascularization, and re-epithelialization in a diabetic mouse wound model, signifying their effectiveness in healing diabetic wounds. Taken together, porous NMs hold significant potential as minimally invasive, injectable treatments that effectively promote tissue integration and regeneration.
10.1021/acsnano.4c10044
Highly Elastic and Strain Sensing Corn Protein Electrospun Fibers for Monitoring of Wound Healing.
ACS nano
Due to the lack of sufficient elasticity and strain sensing capability, protein-based ultrafine fibrous tissue engineering scaffolds, though favorable for skin repair, can hardly fulfill on-spot wound monitoring during healing. Herein, we designed highly elastic corn protein ultrafine fibrous smart scaffolds with a three-layer structure for motion tracking at an unpackaged state. The densely cross-linked protein networks were efficiently established by introducing a highly reactive epoxy and provided the fiber substrates with wide-range stretchability (360% stretching range) and ultrahigh elasticity (99.91% recovery rate) at a wet state. With the assistance of the polydopamine bonding layer, a silver conductive sensing layer was built on the protein fibers and endowed the scaffolds with wide strain sensing range (264%), high sensitivity (gauge factor up to 210.55), short response time (<70 ms), reliable cycling stability, and long-lasting duration (up to 30 days). The unpackaged smart scaffolds could not only support cell growth and accelerate wound closure but also track motions on skin and and trigger alarms once excessive wound deformations occurred. These features not only confirmed the great potential of these smart scaffolds for applications in tissue reconstruction and wound monitoring but also proved the possibility of employing various plant protein ultrafine fibers as flexible bioelectronics.
10.1021/acsnano.3c03087
Leveraging the advancements in functional biomaterials and scaffold fabrication technologies for chronic wound healing applications.
Materials horizons
Exploring new avenues for clinical management of chronic wounds holds the key to eliminating socioeconomic burdens and health-related concerns associated with this silent killer. Engineered biomaterials offer great promise for repair and regeneration of chronic wounds because of their ability to deliver therapeutics, protect the wound environment, and support the skin matrices to facilitate tissue growth. This mini review presents recent advances in biomaterial functionalities for enhancing wound healing and demonstrates a move from sub-optimal methods to multi-functionalized treatment approaches. In this context, we discuss the recently reported biomaterial characteristics such as bioadhesiveness, antimicrobial properties, proangiogenic attributes, and anti-inflammatory properties that promote chronic wound healing. In addition, we highlight the necessary mechanical and mass transport properties of such biomaterials. Then, we discuss the characteristic properties of various biomaterial templates, including hydrogels, cryogels, nanomaterials, and biomolecule-functionalized materials. These biomaterials can be microfabricated into various structures, including smart patches, microneedles, electrospun scaffolds, and 3D-bioprinted structures, to advance the field of biomaterial scaffolds for effective wound healing. Finally, we provide an outlook on the future while emphasizing the need for their detailed functional behaviour and inflammatory response studies in a complex environment for superior clinical outcomes and reduced regulatory hurdles.
10.1039/d2mh00115b
Durable Immunomodulatory Nanofiber Niche for the Functional Remodeling of Cardiovascular Tissue.
ACS nano
Functional remodeling and prolonged anti-inflammatory responses are both vital for repairing damage in the cardiovascular system. Although these aspects have each been studied extensively alone, attempts to fabricate scaffolds that combine these effects have seen limited success. In this study, we synthesized salvianic acid A (SA, danshensu) blocked biodegradable polyurethane (PCHU-D) and enclosed it within electrospun nanofibers to synthesize a durable immunomodulatory nanofiber niche (DINN), which provided sustained SA release during inflammation. Given its excellent processability, mechanical properties, and shape memory function, we developed two variants of the DINN as vascular scaffolds and heart patches. Both these variants exhibited outstanding therapeutic effects in experiments. The DINN was expertly designed such that it gradually decomposes along with SA release, substantially facilitating cellular infiltration and tissue remodeling. Therefore, the DINN effectively inhibited the migration and chemotaxis of inflammatory cells, while also increasing the expression of angiogenic genes. As a result, it promoted the recovery of myocardial function after myocardial infarction and induced rapid reendothelialization following arterial orthotopic transplantation repair. These excellent characteristics indicate that the DINN holds great potential as a multifunctional agent for repairing cardiovascular tissues.
10.1021/acsnano.3c09692
Bioactive Electrospun Fibers: Fabrication Strategies and a Critical Review of Surface-Sensitive Characterization and Quantification.
Taskin Mehmet Berat,Ahmad Taufiq,Wistlich Laura,Meinel Lorenz,Schmitz Michael,Rossi Angela,Groll Jürgen
Chemical reviews
Fabricating a porous scaffold with high surface area has been a major strategy in the tissue engineering field. Among the many fabrication methods, electrospinning has become one of the cornerstone techniques due to its enabling the fabrication of highly porous fibrous scaffolds that are of natural or synthetic origin. Apart from the basic requirements of mechanical stability and biocompatibility, scaffolds are further expected to embody functional cues that drive cellular functions such as adhesion, spreading, proliferation, migration, and differentiation. There are abundant distinct approaches to introducing bioactive molecules to have a control over cellular functions. However, the lack of a thorough understanding of cell behavior with respect to the availability and spatial distribution of the bioactive molecules in 3D fibrous scaffolds is yet to be addressed. The rational selection of proper sets of characterization techniques would essentially impact the interpretation of the cell-scaffold interactions. In this timely Review, we summarize the most popular methods to introduce functional compounds to electrospun fibers. Thereafter, the strength and limitations of the conventional characterization methods are highlighted. Finally, the potential and applicability of emerging characterization techniques such as high-resolution/correlative microscopy approaches are further discussed.
10.1021/acs.chemrev.0c00816
Spatiotemporal Immunomodulation and Biphasic Osteo-Vascular Aligned Electrospun Membrane for Diabetic Periosteum Regeneration.
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
Under diabetic conditions, blood glucose fluctuations and exacerbated immunopathological inflammatory environments pose significant challenges to periosteal regenerative repair strategies. Responsive immune regulation in damaged tissues is critical for the immune microenvironment, osteogenesis, and angiogenesis stabilization. Considering the high-glucose microenvironment of such acute injury sites, a functional glucose-responsive immunomodulation-assisted periosteal regeneration composite material-PLA（Polylactic Acid）/COLI(Collagen I）/Lipo(Liposome）-APY29 (PCLA)-is constructed. Aside from stimulating osteogenic differentiation, owing to the presence of surface self-assembled type I collagen in the scaffolds, PCLA can directly respond to focal area high-glucose microenvironments. The PCLA scaffolds trigger the release of APY29-loaded liposomes, shifting the macrophages toward the M2 phenotype, inhibiting the release of inflammatory cytokines, improving the bone immune microenvironment, and promoting osteogenic differentiation and angiogenesis. Bioinformatics analyses show that PCLA enhances bone repair by inhibiting the inflammatory signal pathway regulating the polarization direction and promoting osteogenic and angiogenic gene expression. In the calvarial periosteal defect model of diabetic rats, PCLA scaffolds induce M2 macrophage polarization and improve the inflammatory microenvironment, significantly accelerating periosteal repair. Overall, the PCLA scaffold material regulates immunity in fluctuating high-glucose inflammatory microenvironments, achieves relatively stable and favorable osteogenic microenvironments, and facilitates the effective design of functionalized biomaterials for bone regeneration therapy in patients with diabetes.
10.1002/advs.202302874
Electrospinning and Electrospun Nanofibers: Methods, Materials, and Applications.
Chemical reviews
Electrospinning is a versatile and viable technique for generating ultrathin fibers. Remarkable progress has been made with regard to the development of electrospinning methods and engineering of electrospun nanofibers to suit or enable various applications. We aim to provide a comprehensive overview of electrospinning, including the principle, methods, materials, and applications. We begin with a brief introduction to the early history of electrospinning, followed by discussion of its principle and typical apparatus. We then discuss its renaissance over the past two decades as a powerful technology for the production of nanofibers with diversified compositions, structures, and properties. Afterward, we discuss the applications of electrospun nanofibers, including their use as "smart" mats, filtration membranes, catalytic supports, energy harvesting/conversion/storage components, and photonic and electronic devices, as well as biomedical scaffolds. We highlight the most relevant and recent advances related to the applications of electrospun nanofibers by focusing on the most representative examples. We also offer perspectives on the challenges, opportunities, and new directions for future development. At the end, we discuss approaches to the scale-up production of electrospun nanofibers and briefly discuss various types of commercial products based on electrospun nanofibers that have found widespread use in our everyday life.
10.1021/acs.chemrev.8b00593
Dissecting the microenvironment around biosynthetic scaffolds in murine skin wound healing.
Science advances
The structural properties of biomaterials play crucial roles in guiding cell behavior and influencing immune responses against the material. We fabricated electrospun membranes with three types of surface topography (random, aligned, and latticed), introduced them to dorsal skin excisional wounds in mice and rats, and evaluated their effects on wound healing and immunomodulatory properties. An overview of different immune cells in the microenvironment with the help of single-cell RNA sequencing revealed diverse cellular heterogeneity in vivo. The time course of immune response was advanced toward an adaptive immunity-dominant stage by the aligned scaffold. In mice without mature T lymphocytes, lack of wound-induced hair neogenesis indicated a regulatory role of T cells on hair follicle regeneration. The microenvironment around scaffolds involved an intricate interplay of immune and cutaneous cells.
10.1126/sciadv.abf0787