Novel injectable adhesive hydrogel loaded with exosomes for holistic repair of hemophilic articular cartilage defect

Hemophilic articular cartilage damage presents a significant challenge for surgeons,characterized by recurrent intraarticular bleeding,a severe inflammatory microenvironment,and limited self-repair capability of cartilage tissue.Currently,there is a lack of tissue engineering-based integrated therapies that address both early hemostasis,anti-inflammation,and long-lasting chondrogenesis for hemophilic articular cartilage defects.Herein,we developed an adhesive hydrogel using oxidized chondroitin sulfate and gelatin,loaded with exosomes derived from bone marrow stem cells(BMSCs)(Hydrogel-Exos).This hydrogel demonstrated favorable injectability,self-healing,biocompatibility,biodegradability,swelling,frictional and mechanical properties,providing a comprehensive approach to treating hemophilic articular cartilage defects.The adhesive hydrogel,featuring dynamic Schiff base bonds and hydrogen bonds,exhibited excellent wet tissue adhesiveness and hemostatic properties.In a pig model,the hydrogel could be smoothly injected into the knee joint cartilage defect site and gelled in situ under fluid-irrigated arthroscopic conditions.Our in vitro and in vivo experiments confirmed that the sustained release of exosomes yielded anti-inflammatory effects by modulating macrophage M2 polarization through the NF-κB pathway.This immunoregulatory effect,coupled with the extracellular matrix components provided by the adhesive hydrogel,enhanced chondrogenesis,promoted the cartilage repair and joint function restoration after hemophilic articular cartilage defects.In conclusion,our results highlight the significant application potential of Hydrogel-Exos for early hemostasis,immunoregulation,and long-term chondrogenesis in hemophilic patients with cartilage injuries.This innovative approach is well-suited for application during arthroscopic procedures,offering a promising solution for addressing the complex challenges associated with hemophilic articular cartilage damage.

Triple-functional bone adhesive with enhanced internal fixation,bacteriostasis and osteoinductive properties for open fracture repair

At present,effective fixation and anti-infection implant materials represent the mainstay for the treatment of open fractures.However,external fixation can cause nail tract infections and is ineffective for fixing small fracture fragments.Moreover,closed reduction and internal fixation during the early stage of injury can lead to potential bone infection,conducive to bone nonunion and delayed healing.Herein,we designed a bone adhesive with anti-infection,osteogenic and bone adhesion fixation properties to promote reduction and fixation of open fractures and subsequent soft tissue repair.It was prepared by the reaction of gelatin(Gel)and oxidized starch(OS)with vancomycin(VAN)-loaded mesoporous bioactive glass nanoparticles(MBGNs)covalently cross-linked with Schiff bases.Characterization and adhesion experiments were conducted to validate the successful preparation of the Gel-OS/VAN@MBGNs(GOVM-gel)adhesive.Meanwhile,in vitro cell experiments demonstrated its good antibacterial effects with the ability to stimulate bone marrow mesenchymal stem cell(BMSCs)proliferation,upregulate the expression of alkaline phosphatase(ALP)and osteogenic proteins(RunX2 and OPN)and enhance the deposition of calcium nodules.Additionally,we established a rat skull fracture model and a subcutaneous infection model.The histological analysis showed that bone adhesive enhanced osteogenesis,and in vivo experiments demonstrated that the number of inflammatory cells and bacteria was significantly reduced.Overall,the adhesive could promote early reduction of fractures and antibacterial and osteogenic effects,providing the foothold for treatment of this patient population.

Exosomes-loaded electroconductive nerve dressing for nerve regeneration and pain relief against diabetic peripheral nerve injury

Over the years,electroconductive hydrogels(ECHs)have been extensively applied for stimulating nerve regeneration and restoring locomotor function after peripheral nerve injury(PNI)with diabetes,given their favorable mechanical and electrical properties identical to endogenous nerve tissue.Nevertheless,PNI causes the loss of locomotor function and inflammatory pain,especially in diabetic patients.It has been established that bone marrow stem cells-derived exosomes(BMSCs-Exos)have analgesic,anti-inflammatory and tissue regeneration properties.Herein,we designed an ECH loaded with BMSCs-Exos(ECH-Exos)electroconductive nerve dressing to treat diabetic PNI to achieve functional recovery and pain relief.Given its potent adhesive and self-healing properties,this laminar dressing is convenient for the treatment of damaged nerve fibers by automatically wrapping around them to form a size-matched tube-like structure,avoiding the cumbersome implantation process.Our in vitro studies showed that ECH-Exos could facilitate the attachment and migration of Schwann cells.Meanwhile,Exos in this system could modulate M2 macrophage polarization via the NF-κB pathway,thereby attenuating inflammatory pain in diabetic PNI.Additionally,ECH-Exos enhanced myelinated axonal regeneration via the MEK/ERK pathway in vitro and in vivo,consequently ameliorating muscle denervation atrophy and further promoting functional restoration.Our findings suggest that the ECH-Exos system has huge prospects for nerve regeneration,functional restoration and pain relief in patients with diabetic PNI.