The challenges posed by delayed atrophic healing and nonunion stand as formidable obstacles in osteoporotic fracture treatment. The processes of type H angiogenesis and osteogenesis emerge as pivotal mechanisms during bone regeneration. Notably, the preconditioning of adipose-derived stem cell (ADSC) exosomes under hypoxic conditions has garnered attention for its potential to augment the secretion and functionality of these exosomes. In the present investigation, we embarked upon a comprehensive elucidation of the underlying mechanisms of hypo-ADSC-Exos within the milieu of osteoporotic bone regeneration. Our findings revealed that hypo-ADSC-Exos harboured a preeminent miRNA, namely, miR-21-5p, which emerged as the principal orchestrator of angiogenic effects. Through in vitro experiments, we demonstrated the capacity of hypo-ADSC-Exos to stimulate the proliferation, migration, and angiogenic potential of human umbilical vein endothelial cells (HUVECs) via the mediation of miR-21-5p. The inhibition of miR-21-5p effectively attenuated the proangiogenic effects mediated by hypo-ADSC-Exos. Mechanistically, our investigation revealed that exosomal miR-21-5p emanating from hypo-ADSCs exerts its regulatory influence by targeting sprouly1 (SPRY1) within HUVECs, thereby facilitating the activation of the PI3K/AKT signalling pathway. Notably, knockdown of SPRY1 in HUVECs was found to potentiate PI3K/AKT activation and, concomitantly, HUVEC proliferation, migration, and angiogenesis. The culminating stage of our study involved a compelling in vivo demonstration wherein GelMA loaded with hypo-ADSC-Exos was validated to substantially enhance local type H angiogenesis and concomitant bone regeneration. This enhancement was unequivocally attributed to the exosomal modulation of SPRY1. In summary, our investigation offers a pioneering perspective on the potential utility of hypo-ADSC-Exos as readily available for osteoporotic fracture treatment. Graphical

The treatment of open tibial shaft fractures is challenging. External fixation (EF) is comparatively safe in treating these open injuries, meanwhile it has the advantages of easy application, minimal additional disruption, and convenient subsequent soft tissue repair. Nevertheless, its application is accompanied by a series of problems in alignment and bone healing. Therefore, limited internal fixation (LIF), such as cortical screws, has been used based on the external fixator for better therapeutic effect. The aim of this study is to compare the outcomes of EF combined with LIF and simple EF in the management of open tibial shaft fractures, evaluating the efficacy and safety of using the combined technique in treating such fractures. From January 2012 to December 2016, patients with open tibial shaft fractures treated with EF with or without LIF augmentation were identified. A total of 152 patients were included in the analysis, and there were 85 patients in the simple external fixation group and 67 patients in the EF-LIF group. General assessment indicators included the direct cost of hospitalization and the times of first surgery, full weight bearing, and complete union. Infections and complications in union or limb alignment were compared as primary outcomes. Additionally, the number of patients who changed the fixation system for various reasons were analysed. Effective follow-up of all participants for statistical analysis was obtained. The follow-up time averaged 17.15 months (range: 12.00 to 24.00 months) in the EF group and 16.20 months (range: 12.00 to 19.00 months) in the EF-LIF group. Combined fixation provided shortened time to bear full weight and achieve complete bone union, while requiring additional first surgery time. No significant difference was found in infection rates or direct cost of hospitalization. Delayed union and non-union in the EF-LIF group were significantly decreased (20.9% versus 40.0, 1.5% versus 14.1%, p < 0.05). In limb alignment, patients with combined fixation exhibited reduced malreduction, loss of reduction, and malunion. In terms of secondary fixation, the EF-LIF group showed a markedly lower incidence (5.8% versus 34.1%, p < 0.001). Compared with simple EF, combined fixation is an effective and safe alternative for management of open tibial diaphyseal fractures. It provides superior initial reduction, better stability and decreases the risk of inferior alignment and delayed union without increasing the risk of infection.

The healing of infected tendons is hindered by mechanical dysfunction, tissue adhesion, bacterial colonization, and immune imbalance. Inspired by the biphasic “adhesion-lubrication” structure of tendon sheaths, we developed a Janus hydrogel, named HAPP@H-EXO, for spatiotemporal repair. The material exhibits antifatigue properties and redistributes mechanical stress through a dynamic network formed by norbornylated PVA and boronic acid-modified hyaluronic acid-PVA. Its high-adhesion side integrates tissue via borate and hydrogen bonds, whereas the lotus leaf-induced low-adhesion side prevents postsurgical adhesion. The incorporation of oligo-polyethyleneimine and phenylboronic acid groups traps and kills bacteria, overcoming resistance. The pH-responsive release of hypoxic tendon stem cell exosomes reprogrammes macrophages via inhibition of the NF-κB pathway, reducing inflammation and promoting regeneration. In an infected Achilles tendon model, HAPP@H-EXO eliminated MRSA, suppressed early inflammation, and enhanced regeneration. Within 8 weeks, it significantly improved biomechanical strength, prevented adhesion, and restored motor function, establishing a mechanoimmunotherapeutic strategy for infected tissue regeneration.

The wounds at the joints are subject to repeated pulling. This not only causes repeated rupture and bleeding of new granulation tissue, but also causes excessive exogenous mechanical stimulation of cell populations, leading to excessive cell proliferation and vascular proliferation at the trauma site. Inspired by the energy conversion of tendons, the “energy transit station” hydrogel is designed. When applied to dynamic joint wounds, the rigid cross‐linked network of hydrogels rapidly absorbs wound edge stress by elastic deformation and stores them as elastic potential energy in the topological network matrix, driving the hydrogels to exhibit programmable elastic recoil capabilities. Thus, the “energy transfer station” hydrogel not only shields stress concentration in sports injuries, but also reprograms energy forms to provide reasonable biomimetic contraction for wounds. In vivo research, compared with the control group (83.06%), this hydrogel can significantly accelerate the healing process of sports injuries (99.87%). The “energy transit station” property significantly downregulated the En1 lineage‐positive fibroblast population (only 9.21% of the control group) and coordinated the activation of α‐SMA‐positive myofibroblasts (only 14.62% of the control group). This research provides an innovative strategy for high‐quality healing of joint wounds through the conversion and re‐transmission of energy.