BACKGROUND:Osteoporotic vertebral compression fractures (OVCFs) are frequently underdiagnosed worldwide due to their subtle radiographic presentation and the inherently low contrast of x-ray images. This diagnostic challenge is further compounded by the limited availability of high-quality annotated datasets. PURPOSE:In this study, we proposed OVCFinder, a deep-learning-based two-stage cascade model designed for the accurate detection of OVCFs and the classification of old and new fractures in x-ray images. METHODS:The segmentation stage is built upon an enhanced DeepLabv3+ backbone, refined to improve local feature sensitivity by reducing the output stride, replacing atrous convolutions with standard ones to suppress noise, and incorporating multiscale convolutional layers to capture morphological variations. In the classification stage, a model library comprising nine diverse deep learning architectures supports both binary and three-class classification tasks, effectively distinguishing normal, new, and old fractures. RESULTS:Experimental results demonstrate that the OVCFinder's performance exceeds that of single-stage detection frameworks. Furthermore, for binary classification, this cascade model obtained an average weighted accuracy of 62.72%, weighted precision of 72.90%, weighted recall of 62.72%, and weighted F1-score of 66.69%. The best individual model performances were achieved by AlexNet, with an accuracy of 70.49%, and VGG16, with an F1-score of 72.36%. These results notably exceeded the average performance of expert physicians (53.42% weighted accuracy, 53.51% weighted precision, 53.42% weighted recall, and 53.16% weighted F1 score). In the more challenging ternary classification task, this model achieved an average weighted accuracy of 37.05%, weighted precision of 50.16%, weighted recall of 22.91%, and weighted F1 score of 30.62%, with the upper-bound performance (ResNet152 reaching 48.09% accuracy and 39.27% F1 score) substantially surpassing that of human experts (39.74% weighted accuracy and 29.49% weighted F1 score). CONCLUSIONS:This work represents the first application of a segmentation-classification cascade strategy for OVCF analysis, enabling end-to-end vertebral segmentation and fracture characterization directly on x-ray images. By decomposing the task, applying targeted optimizations, and adopting a modular design, OVCFinder achieves notable advantages in recognition accuracy, robustness, and interpretability. The OVCFinder's performance in both tasks demonstrates its clinical applicability and diagnostic superiority over conventional approaches, offering a low-cost, high-reliability auxiliary diagnostic tool for use in primary healthcare settings.

Aging is a gradual process leading to the decline of physiological functions across cells, organs, tissues, systems, and the surrounding microenvironment, particularly affecting the musculoskeletal system. Bone aging often presents with osteoporosis and impaired osteogenic niche, thereby increasing fracture risk and decreasing regenerative capacity. Therefore, bone aging and osteoporotic bone defects have become a significant challenge in clinical practice. Tissue-engineered scaffolds are of significant importance in managing osteoporotic bone defects by providing mechanical support, facilitating bone regeneration and repair. They can also serve as a vehicle for drugs or factors for osteoporosis management, thereby enabling localized targeted therapy. The local release of active pharmaceutical agents for the treatment of osteoporosis via biomaterials could serve to reduce the occurrence of systemic side effects, while improving the local aging metabolic microenvironment and immune microenvironment. This review presents a comprehensive discussion of the mechanisms and treatment methods of osteoporosis. The scaffolds used for osteoporotic bone defects are also reviewed. We conducted an in-depth analysis of the impact of diverse preparation techniques and modifications on the osteogenic properties of the scaffolds, and reviewed different materials of drug delivery scaffolds for the repair of osteoporotic bone defects. Finally, we put forward our scientific concept regarding the treatment of bone aging and osteoporotic bone defects. We hope to provide a theoretical basis and research ideas for further in-depth studies on treating osteoporosis and bone aging.

The treatment of bone defects in osteoporotic (OP) patients remain a significant clinical challenge. The most important and challenging task is to promote sufficient bone formation in the early stage and effectively inhibit bone resorption all period of bone healing. Unfortunately, the efficacy of current strategies falls short of meeting this requirement. In this study, we developed a dual-delivery system that allows spatiotemporal release of bone marrow stem cell-derived exosomes (BMSC-Exo) and alendronate (Aln) by core-shell nanofiber to match the spatiotemporal dynamics of bone healing and effectively treat OP bone defects. Core-shell polycaprolactone/polyvinyl alcohol (P/PVA) nanofibers were fabricated through coaxial electrospinning, incorporating Aln within the core layer and BMSC-Exo functionalized onto the surface of nanofiber via chemical modification with polyethyleneimine (PEI). Physicochemical characterization confirmed the successful fabrication of PEI@P/PVA-Aln nanofibers, which exhibited excellent mechanical strength (22.77 MPa), hydrophilicity (9.66°), and enabled the spatiotemporal release of BMSC-Exo and Aln. In vitro experiments showed that Exo-PEI@P/PVA-Aln scaffold effectively promoted osteogenic differentiation by miR-486 in the BMSC-Exo through regulation of the PTEN/AKT signaling axis and significantly reduced osteoclastic differentiation. Under a rat OP cranial defect model, the Exo-PEI@P/PVA-Aln scaffold demonstrated substantially enhanced bone repair efficiency after 4 and 10 weeks. To conclude, our results showed that the dual delivery of BMSC-Exo and Aln with spatiotemporal release orchestrates osteoblastic and osteoclastic activity, providing a potential strategy to facilitate the regeneration of OP bone defects.

Mesenchymal stem cells (MSCs) within the shoulder joint serve as a critical progenitor pool for regenerating the fibrocartilaginous enthesis during rotator cuff repair. However, the chondrogenic potential of MSCs across distinct rotator cuff sites, along with the underlying molecular mechanisms, remains to be elucidated. We performed a comparative analysis of human subacromial bursa-derived MSCs (sMSCs) and rotator cuff enthesis-derived MSCs (rMSCs). By integrating functional chondrogenic assays with longitudinal bulk and single-cell RNA sequencing, we reconstructed source-specific differentiation trajectories and identified key regulatory drivers. rMSCs exhibited superior chondrogenic potency compared to sMSCs. Transcriptional profiling identified a region-specific pro-chondrogenic module in rMSCs driven by the transcription factor SIX2. Single-cell atlas construction revealed that tissue origin dictates lineage fate: rMSCs were enriched for a high-potency SIX2+ progenitor population that differentiated into metabolic-active S100A2+ chondrocytes. Conversely, sMSCs were dominated by DPP4+ progenitors that preferentially bifurcated into an aberrant CXCL8+ inflammatory trajectory. Mechanistically, we demonstrated that SIX2 acted as a competency factor, coordinating early proliferative expansion with late-stage matrix assembly and, crucially, active suppression of inflammatory signaling. Accordingly, lentiviral overexpression of SIX2 in sMSCs was sufficient to rescue their chondrogenic defects and rewire their trajectory toward a regenerative phenotype. Our findings define the transcriptional hierarchy of shoulder-resident progenitors, identifying SIX2 as a master regulator that couples chondrogenesis with immune evasion. This establishes a molecular framework for precision cell sourcing and rational design of lineage-specific therapies.

The repair of peripheral nerve defects necessitates the use of nerve guidance conduits (NGCs). However, the diameter mismatch between NGC and nerve, the complex suturing process, and the slow rate of axonal growth collectively leads to unsatisfactory nerve regeneration. Therefore, an ideal NGC should be diameter-adaptive, suture-free, and capable of providing electrical signals to enhance nerve regeneration. Inspired by the heat shrink tubing, we present an IR-triggered contractile and suture-free NGC with magnetoelectric responsiveness named P/A/PFeC@PAA. P/A/PFeC@PAA is composed of Pluronic F127 diacrylate mixed with Pluronic F127 (collectively referred to as P), alginate (A), and polydopamine-chelated carbon nanotube–Fe3O4 nanohybrid (PFeC), with an adhesive inner layer formed by polymerized acrylic acid and acrylic acid-N-hydroxysuccinimide (PAA). Under IR irradiation, the photothermal effect of PFeC induces the micellar aggregation of P and subsequent contraction of conduit, while PAA mediates adhesion to the nerve stumps, together enabling diameter-adaptive, suture-free repair. In addition, under an alternating magnetic field, anisotropic PFeC generates electrical stimulation in a noninvasive and controllable manner. This multifunctional NGC can greatly simplify the surgical procedure and provide effective post-operative support for nerve regeneration.

ABSTRACT:Peripheral nerve injury often results in irreversible functional deficits that are caused by chronic denervation. Although surgical techniques for nerve repair have advanced, a lack of understanding of the cellular dynamics in the distal nerve microenvironment has impeded the development of effective interventions. In the present study, we constructed a longitudinal single-nucleus transcriptomic atlas of distal sciatic nerve stumps from rats with complete transection injuries across five time points (0, 14, 28, 60, and 90 days postinjury). Sequencing of 63,033 nuclei revealed dynamic state transitions that spanned multiple cell types throughout nerve degeneration. At 14 days post-injury, Schwann cells proliferated and adopted a repair phenotype, whereas immune cells persisted following Wallerian degeneration alongside transient apoptosis in other stromal populations. Diverse cell types sustained robust functional activity supporting axonal regeneration until 28 days post-injury. By 60 days post-injury, persistent denervation triggered the irreversible deterioration of cellular states with minimal changes in cell numbers; this was marked by a loss of Schwann cell regenerative capacity and a pro-inflammatory shift in immune responses. By 90 days post-injury, accelerated apoptosis caused pronounced cellular loss, including a severe decline in Schwann cells. Cell-cell communication analysis identified Schwann cells as central signaling hubs that are essential for coordinating multicellular responses and regulating the microenvironment. Critically, our findings identify 28 days post-injury as a critical threshold for effective nerve regeneration. Within 28 days of injury, distal nerve segments maintain a cellular microenvironment that is capable of actively supporting regeneration; however, beyond 28 days post-injury, this supportive capacity markedly declines because of progressive chronic changes in the Schwann cell phenotype and axonal microenvironment. These results provide mechanistic insights into the pathophysiology of chronic denervation and establish a foundation for targeted interventions that are designed to extend the regenerative window and overcome barriers to nerve repair.

BACKGROUND AND AIMS:Severe peripheral nerve injury (PNI) remains a major clinical challenge, and functional recovery after conventional neurorrhaphy is often unsatisfactory due to fascicular mismatch, suture tension, and limited Schwann cell viability. To address these limitations, we previously developed a small-gap chitosan-based conduit that provides a controlled microenvironment for regenerative interventions. This study aimed to investigate whether SOX5 overexpression enhances Schwann cell regenerative potential and, when combined with this conduit, synergistically promotes peripheral nerve regeneration. METHODS:Schwann cells were transduced with SOX5 lentivirus and assessed for proliferation, migration, and neurotrophic factor secretion in vitro. In a rat sciatic nerve transection model (2-mm gap), animals received a chitosan conduit with intraluminal injection of SOX5 lentivirus. Histological, electrophysiological, and behavioral assessments were conducted at 12 weeks post-surgery. RESULTS:SOX5 overexpression significantly enhanced Schwann cell proliferation, migration, and secretion of BDNF, NGF, CNTF, and VEGF, while maintaining the dedifferentiated repair phenotype. In vivo, the combination of SOX5 lentivirus and chitosan conduit improved axonal regeneration, reduced muscle atrophy, and increased conduction velocity and locomotor recovery relative to the empty conduit group. INTERPRETATION:Lentivirus-mediated SOX5 overexpression drives Schwann cells toward a repair phenotype and, when integrated with a small-gap chitosan-based conduit, effectively promotes structural and functional nerve regeneration.

Peripheral nerve injury (PNI) poses a major clinical challenge, frequently resulting in chronic pain, muscle atrophy, and long-term functional impairment. While autologous nerve grafting remains the gold standard for repairing long-gap defects, its application is limited by donor-site morbidity and limited tissue availability. Nerve guidance conduits (NGCs) have emerged as promising alternatives; however, their efficacy remains suboptimal, primarily because most fail to recapitulate the spatiotemporally coordinated regenerative microenvironment required for robust axonal extension, timely remyelination, and durable neurovascular integration. Key limitations of current designs include an inability to balance the bioactivity of natural materials with the tunability of synthetic polymers, insufficient nutrient and oxygen delivery for long-gap repair, and a lack of dynamic, stage-specific regulation of the healing process. Consequently, microenvironment reconstruction represents the central bottleneck to achieving effective regeneration. This review synthesizes recent advances in purposefully rebuilding the NGC microenvironment across three interdependent dimensions: (i) activation and functional regulation of Schwann cells; (ii) immunomodulation to resolve inflammation while promoting repair; (iii) angiogenesis to ensure metabolic support. We place special emphasis on biomaterial strategies, particularly advanced hydrogels that integrate physical, biochemical, and dynamic cues for spatiotemporally programmed regeneration. Finally, we outline design principles and translational considerations for next-generation NGCs aimed at closing the efficacy gap with autografts.

Postmenopausal osteoporosis, driven by estrogen-deficient bone loss, faces therapeutic challenges due to current drug side effects and off-target effects. While curcumin demonstrates dual osteogenic and antiresorptive activity, its clinical translation is hindered by poor aqueous solubility, chemical instability, and photolability. A bone-targeted delivery system using osteoblast-like cell membrane-coated nanoparticles was designed to enhance precision and efficacy for treating osteoporosis. Through systematic database analysis, osteoblast-like cell membrane containing CXCR4 and TNF-α receptors were selected to coat curcumin-loaded PLGA nanoparticles (Cur@NPs), namely OM/Cur@NPs. OM/Cur@NPs and Cur@NPs were injected into ovariectomized (OVX) mice to comparatively assess in vivo bone-targeting. Additionally, leveraging the specific binding capability of TNFR to TNF-α, we evaluated the effects of cell membrane-coated nanoparticles on osteoblasts and osteoclasts formation under TNF-α stimulation in vitro. We further evaluated the anti-osteoporotic efficacy of OM/Cur@NPs in vivo by micro-CT analysis (BMD, Tb.BV/TV, Tb.N, Tb.Th, Tb.Sp) and histological examination of bone formation and resorption. The OM/Cur@NPs group exhibited higher bone accumulation compared to Cur@NPs in OVX mice. Notably, these biomimetic nanoparticles neutralized TNF-α, thereby enhancing osteoblastic functions, while attenuating the synergistic pro-osteoclastogenic effects of TNF-α and RANKL. In vivo studies demonstrated that the OM/Cur@NPs-treated group showed superior radiographic bone parameters (BMD, Tb.BV/TV, Tb.N, Tb.Th, Tb.Sp) compared to other experimental groups. Furthermore, histological examination revealed the dual efficacy of OM/Cur@NPs in enhancing bone formation while inhibiting bone resorption in osteoporotic mice. This dual-functional platform couples targeted drug delivery with inflammatory microenvironment modulation and holds promise for metabolic bone disorders.

The repair of osteoporotic bone defect (OBD) continues to be challenged by the persistent inflammatory imbalance and impaired osteogenesis. Inspired by the immunomodulatory role of macrophages, we developed a multifunctional bone repair platform consisting of macrophage membrane-liposome hybrid nanovesicles (MM-Lipo) embedded in the GelMA hydrogel. The MM-Lipo nanovesicles, which present membrane-anchored cytokine receptors, effectively scavenged excess RANKL, TNF-α, IL-6 at the defect sites, thereby regulating the local microenvironment. The aqueous core of the nanovesicles allowed for the encapsulation of the hydrophilic teriparatide (PTH 1–34). The GelMA hydrogel served as a sustained-release reservoir, facilitating the sequential delivery of both nanovesicles and drug to promote osteogenic differentiation. In vitro, MM-Lipo efficiently depleted cytokines, inhibited RANKL-induced osteoclastogenesis, and reversed the inhibitory effects TNF-α on osteoblast function. The teriparatide-loaded formulation (MM-Lipo@PTH) further upregulated the expression of osteogenic markers (OSX, OCN) and promoted mineralized matrix deposition. In the mouse OBD model, a single implantation of the GelMA/MM-Lipo@PTH hydrogel rebalanced osteoclast and osteoblast activity, accelerated bone regeneration, and supported well-organized collagen architecture. This synergistic strategy integrates the cytokines-scavenging capability of biomimetic membrane with the controlled, sequential release properties of hydrogel, offering a promising therapeutic platform for inflammation-associated metabolic bone disorders.Abbreviations: ALP, Alkaline phosphatase; ALT, Alanine Aminotransferase; AST, Aspartate aminotransferase; BCA, Bicinchoninic acid; BCIP/NBT, 5-bromo-4-chloro-3-indolyl phosphate/nitro blue tetrazolium; BMSC, bone mesenchymal stem cells; BUN, Blood urea nitrogen; CCK-8, Cell counting kit-8; CREA, Creatinine; DAPI, 4′,6-diamidino-2-phenylindole; Dil, 1,1′-Dioctadecyl-3,3,3′,3′-Tetramethylindocar bocyanine Perchlorate; DiO, 3,3′-Dioctadecyloxacar bocyanine perchlorate; ECL, Enhanced chemiluminescence; EDTA, Ethylenediaminetetraacetic acid; ELISA, Enzyme-linked immunosorbent assay; FBS, Fetal bovine serum; FRET, Förster resonance energy transfer; GelMA, Gelatin methacryloyl; H&E, hematoxylin and eosin; IL-6, Interleukin-6; LAP, Lithium phenyl-2,4,6-trimethylbenzoylphosphinate; α-MEM, α-minimum essential medium; OCN, Osteocalcin; OSX, Osterix; PBS, Phosphate buffered saline; PVDF, Polyvinylidene fluoride; RANKL, Receptor activator of nuclear factor-κ B ligand; SDS-PAGE, Sodium dodecyl sulfate–polyacrylamide gel electrophoresis; TBST, Tris-buffered saline with tween-20; TNF-α, Tumor necrosis factor α; TRAP, Tartrate-resistant acid phosphatase; TRITC, Tetramethylrhodamine isothiocyanate.

Bone mesenchymal stem cells (BMSCs) are multipotent progenitors with significant potential for bone tissue engineering and regenerative medicine. This study compared the mitochondrial imaging and transcriptome of BMSCs under two-dimensional (2D) and three-dimensional (3D) culture conditions during osteogenesis. 2D BMSCs were induced toward osteogenesis for 7, 14, and 21 days, while 3D BMSCs were induced for 21 days. Osteogenic mineralization was assessed by Alizarin Red S (ARS) staining, and whole-transcriptome sequencing (RNA-Seq) was performed to elucidate gene expression profiles. Furthermore, mitochondrial morphology in live cells was monitored at 0, 7, 14, and 21 days of 2D osteogenic differentiation to observe the mitochondrial changes. High-Sensitivity Structured Illumination Microscopy (HIS-SIM) imaging showed that mitochondrial morphology in BMSCs underwent a shift toward elongated and interconnected networks over time. The transcriptional profile showed that genes associated with skeletal morphogenesis, bone development, and extracellular matrix organization were significantly upregulated in 3D culture systems. These findings indicate that 3D culture is associated with a transcriptional profile enriched in pathways commonly observed during in vivo osteogenesis, which can inform scaffold-based bone-regeneration strategies.

Background: Peripheral Nerve Injury often cause severe functional impairments and long-term disability. There are various surgical methods to treat PNI, however they all have different shortcomings such as limited donor nerve choices and mismatch of nerve diameters. In addition, effective nerve function recovery also requires continuous nutritional support. Our study focused on the outcome of long-term resveratrol (RSV) supplementation in combination with small gap chitin conduits with variated diameters to promote nerve transfer repair. Methods: We constructed SD rat nerve transfer model with small gap conduit for tibial nerve repair. Then the rats were divided into saline, RSV, mecobalamin, and sham group, which receives different gavage treatments respectively. 16 weeks after surgery, the functional recovery of the tibial nerve was assessed in each group of rats. Results: Compared to the saline group, the RSV group and mecobalamin group showed enhanced performance in both motor function and nerve conduction, as well as improved histomorphology of both nerve and muscle fibers. Conclusion: Long-term RSV supplementation significantly improved functional recovery of tibial nerve after nerve transfer in small gap conduit with variated diameters.

BACKGROUND:The repair technology of peripheral nerve injuries has made great progress, but the simultaneous repair and promotion of nerve regeneration in multiple distal nerves remains a challenging task. The current cylindrical nerve conduits are unsuitable for nerve transposition repair. This study aims to assess the effect of conical chitosan conduits (different inner diameters at both ends) on nerve transposition repair, in conjunction with methylcobalamin (MeCbl). METHODS:In this study, a conical chitosan conduit was used to bridge a 2 mm defect between the proximal common peroneal nerve and distal tibial nerve and common peroneal nerve in rats. Additionally, we administered MeCbl at various concentrations to evaluate post-surgical adjuvant treatment effect. At 16 weeks post-surgery, gait analysis, electrophysiology testing, transmission electron microscopy (TEM) observation, toluidine blue staining, immunofluorescence staining, muscle wet weight determination and Masson's trichrome staining were performed to assess nerve regeneration and reinnervation of gastrocnemius. RESULTS:Gross observations did not reveal the formation of neuromas after bridging the distal nerves in each group. In terms of motor function (**p < 0.01), compound muscle action potential (CMAP) amplitude and latency (**p < 0.01), the quantity of regenerated nerve fibers, muscle fiber morphology and other parameters (**p < 0.01), 200 μg/kg MeCbl administration as a supplementary treatment had a significant positive impact compared to the chitosan conduit+normal saline (Chi/NS) group. CONCLUSIONS:Our findings demonstrated that conical chitosan conduits combined with MeCbl can effectively promote nerve transposition repair following multiple distal nerve injuries.

Bone aging diseases, including osteoporosis and osteoarthritis, present significant global health challenges, particularly in countries experiencing demographic aging. Conventional treatment strategies such as pharmacotherapy and lifestyle adjustments frequently yield suboptimal therapeutic outcomes and are carry risks of long-term adverse effects. In recent years, biomembrane-derived nanoparticles have emerged as promising candidates for advanced drug delivery systems to overcome these limitations. By encapsulating therapeutic agents within biomembranes (cell membrane, extracellular vesicles), these systems enhance biocompatibility, prolong circulation time, and enable targeted delivery to pathological sites. Moreover, biomembranes can be functionally modified to optimize their therapeutic performance. In this review, we explore the pathophysiology of bone aging diseases, current treatment approaches, and the development of biomembrane-derived nanoparticles, with a focus on their potential applications in osteoporosis and osteoarthritis. These innovative delivery systems offer the potential to improve treatment efficacy and minimize side effects, thereby laying the foundation for clinical translation in the future.

Background: Peripheral nerve injury is a challenging orthopedic issue in clinical management that often leads to limb dysfunction or even disability in severe cases. A thorough exploration of the repair process of peripheral nerve injury and the underlying mechanism contributes to formulate more effective therapeutic strategies. Methods: In the present study, we established a sciatic nerve transection injury model in Sprague-Dawley (SD) rats. A 12-week compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis was then performed via sleeve jointing the proximal common peroneal nerve to the distal tibial nerve and common peroneal nerve, with a 2 mm interval. Compensatory repair via small gap amplification was observed via gross observation of nerve specimen, osmic acid staining, and electrophysiological stimulation of sciatic nerve branches of the tibial and common peroneal nerve. Rat limbs were observed, and the functional recovery of effector muscles of the gastrocnemius and tibialis anterior muscles was assessed through weighing the muscle wet weight, Hematoxylin and Eosin (H&E) staining, and muscle strength detection. H&E staining, Masson staining, and toluidine blue staining were performed to observe the morphological changes of the dorsal root ganglion. Positive expressions of key proteins involved in the Phosphatase and tensin homologue deleted on chromosome ten (PTEN)-protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, including PTEN, AKT, mTOR, Toll-like receptor 4 (TLR4), and Caspase9 in the dorsal root ganglion during compensatory repair of sciatic nerve after injury via small gap amplification, were detected by immunohistochemical staining. Results: It is found that the compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis via sleeve jointing effectively restored the continuity, number of myelinated nerve fibers, and nerve conduction velocity. It promoted toe abduction recovery, improved muscle fiber morphology and increased the wet weight and muscle strength of the gastrocnemius muscle and tibialis anterior muscle. Moreover, it increased the number of neurons and nerve fibers, and improved their morphology. Downregulated PTEN, TLR4, and Caspase9 in the dorsal root ganglia and upregulated AKT and mTOR were observed after small gap amplification than those of the transection injury group, which were closer to those of the control group. Conclusions: Compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis via sleeve jointing can restore the morphology and function of the sciatic nerve, effector muscles, and corresponding dorsal root ganglia by activating the PTEN-AKT/mTOR signaling pathway in the dorsal root ganglia. Our findings provide novel therapeutic targets for peripheral nerve injuries.

Treating severe peripheral nerve injuries is difficult. Nerve repair with conduit small gap tubulization is a treatment option but still needs to be improved. This study aimed to assess the use of microgels containing growth factors, along with chitosan-based conduits, for repairing nerves. Using the water-oil emulsion technique, microgels of methacrylic alginate (AlgMA) that contained vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) were prepared. The effects on rat Schwann cells (RSC96) and human umbilical vein endothelial cells (HUVECs) were evaluated. Chitosan-based conduits were fabricated and used in conjunction with microgels containing two growth factors to treat complete neurotmesis in rats. The results showed that the utilization of dual growth factor microgels improved the migration and decreased the apoptosis of RSC96 cells while promoting the growth and formation of tubes in HUVECs. The utilization of dual growth factor microgels and chitosan-based conduits resulted in notable advancements in the regeneration and myelination of nerve fibers, recovery of neurons, alleviation of muscle atrophy and recovery of neuromotor function and nerve conduction. In conclusion, the use of dual growth factor AlgMA microgels in combination with chitosan-based conduits has the potential to significantly improve the effectiveness of nerve repair.

The clinical treatment of osteosarcoma faces great challenges of residual tumor cells leading to tumor recurrence and irregular bone defects difficult to repair after surgery removal of the primary tumor tissue. We developed an injectable and in-situ cross-linkable hydrogel (named MOG hydrogel) using MgO2 nanoparticles and dopamine-conjugated gelatin as main components. MgO2 was rationally designed as a multifunctional active ingredient to mediate in situ gelation, tumor therapy, and bone repair sequentially. The 10MOG (with 10 mg/mL MgO2 content) showed excellent gel stability, injectability, shape adaptability, tissue adhesion, and rapid hemostatic ability. Importantly, 10MOG exhibited ideal sequential H2O2 and Mg2+ release property. The released H2O2 synergized with photothermal therapy for enhanced tumor recurrence suppression, and the sustainable Mg2+ release efficiently promoted bone regeneration. The MOG hydrogel, possessing excellent on-demand antitumor and osteogenic capabilities in vitro and in vivo, exhibited tremendous potential in the clinical application for challenging postsurgical osteosarcoma treatment.

FK506(Tacrolimus) is a systemic immunosuppressant approved by the U.S. Food and Drug Administration. FK506 has been shown to promote peripheral nerve regeneration, however, its precise mechanism of action and its pathways remain unclear. In this study, we established a rat model of sciatic nerve injury and found that FK506 improved the morphology of the injured sciatic nerve, increased the numbers of motor and sensory neurons, reduced inflammatory responses, markedly improved the conduction function of the injured nerve, and promoted motor function recovery. These findings suggest that FK506 promotes peripheral nerve structure recovery and functional regeneration by reducing the intensity of inflammation after neuronal injury and increasing the number of surviving neurons.

Over the past two decades, advances in arthroscopic and minimally invasive surgical techniques have led to significant growth in sports medicine surgery. Implants such as suture anchors, interference screws, and endo-buttons are commonly used in these procedures. However, traditional implants made of metal or inert materials are not absorbable, leading to complications that affect treatment outcomes. To address this issue, absorbable materials with excellent mechanical properties, good biocompatibility, and controlled degradation rates have been developed and applied in clinical practice. These materials include absorbable polymers, absorbable bioceramics, and absorbable metals. In this paper, we will provide a comprehensive summary of these absorbable materials from the perspective of clinicians, and discuss their clinical applications and related research in sport medicine.

Severe peripheral nerve injuries, such as deficits over long distances or proximal nerve trunk injuries, pose complex reconstruction challenges that often result in unfavorable outcomes. Innovative techniques, such as nerve transposition repair with conduit suturing, can be employed to successfully treat severe peripheral nerve damage. However, cylindrical nerve guides are typically unsuitable for nerve transposition repair. Furthermore, angiogenic and neurotrophic factors are necessary to stimulate the emergence of axonal lateral sprouts, proximal growth, and the rehabilitation of neuron structures and functions. In the current study, we used chitosan to make chitin conduits with different inner diameters at both ends, combined with gelatin methacrylate hydrogels that can continuously release dual growth factors, namely, the vascular endothelial growth factor (VEGF) and the nerve growth factor (NGF), and evaluated its impact on nerve transposition repair in rats. At 16 weeks after the operation, our findings showed that the conduit combined with the dual growth factor hydrogel significantly improved the restoration of both motor and conduction functions of the nerve. In addition, histological analysis showed significant recovery of nerve fibers, target muscles, and neurons. In conclusion, the combination of chitin conduits with different inner diameters and dual growth factor hydrogels can significantly improve the effect of nerve transposition repair, which has important potential clinical value.