Biomimetic Periosteum Induces Neurovascularized Bone Regeneration

Bone defects are great challenges for orthopedics.The current repair effect of implant materials can not meet the demand.Periosteum is extremely important for bone defects.There are a lot of vessels and nerves in periosteum.In the process of fracture repair,the repair of nerves and blood vessels is carried out before bone repair,which also shows that nerves and blood vessels have an important starting and regulating role before bone repair.It is very important to construct biomimetic periosteum that can promote the repair of nerves and blood vessels to repair bone defects.In this study,the biomimetic periosteum was constructed by electrospinning,and different components were loaded to induce the repair of nerves or blood vessels,thus promoting the repair of bone defects.There are three body in the research:1 Small Intestinal Submucosa Biomimetic Periosteum Promotes Bone RegenerationObjective: Critical bone defects are a significant problem in clinics.The periosteum plays a vital role in bone regeneration.A tissue-engineered periosteum(TEP)has been a novel strategy for bone defect repairs.Methods: In this experiment,a biomimetic periosteum was fabricated by using coaxial electrospinning technology with decellularized porcine small intestinal submucosa(SIS)as the shell and polycaprolactone(PCL)as the core.In vitro,the effects of the biomimetic periosteum on Schwann cells,vascular endothelial cells,and bone marrow mesen-chymal stem cells were detected by a scratch test,an Ed U,a tube-forming test,and an osteogenesis test.In vivo,HE staining was used to evaluate the effect of the biomimetic periosteum on bone regeneration.Results: In vitro experiments showed that the biomimetic periosteum could significantly promote the formation of angiogenesis,osteogenesis,and repaired Schwann cells(SCs).In vivo experiments showed that the biomimetic periosteum could promote the repair of bone defects.Conclusions: The biomimetic periosteum could simulate the structural function of the periosteum and promote bone repair.This strategy may provide a promising method for the clinical treatment of skull bone defects.2 Endogenous Electric Field-Coupled PD@BP Biomimetic Periosteum Promotes Bone Regeneration through Sensory NerveObjective: To treat bone defects,repairing the nerve-rich periosteum is critical for repairing the local electric field.In this study,an endogenous electric field is coupled with 2D black phosphorus electroactive periosteum to explore its role in promoting bone regeneration through nerves.Methods: TEM and SEM are used to observe the electrically active biomimetic periosteum.Here,the in vitro effects exerted by the electrically active periosteum on the transformation of Schwann cells into the repair phenotype,AIS and DCV,and bone marrow mesenchymal stem cells were assessed using SEM,immunofluorescence,and calcium ion probes.Micro-computed tomography and other in vivo techniques are used to study the effects of the electrically active periosteum on bone regeneration.Results: The electrically active periosteum stimulates Schwann cells into a neuroprotective phenotype,enhances the AIS effect of sensory neurons,regulates DCV transport,and releases neurotransmitters,promoting the osteogenic transformation of bone marrow mesenchymal stem cells.Conclusions: The results show that the electrically active periosteum promotes nerveinduced osteogenic repair,providing a potential clinical strategy for bone regeneration.3 Exosome engineering biomimetic periosteum is used for neurovascular bone regenerationObjective: Repairing critical bone defects is a complex problem in the clinic.The periosteum rich in nerve plays a vital role in initiating and regulating bone regeneration.However,current studies have paid little attention to repairing nerves in the periosteum to promote bone regeneration.Thus,it is essential to construct bionic periosteum with the targeted injured nerves in the periosteum.Methods: We coupled phosphatidylserine(PS)targeted aptamers with repair Schwann cell exosomes to construct exosome@aptamer(EA),and then through PEI,EA was successfully built on the surface of the electrospun fiber,which was PCL@PEI@exosome@aptamer(PPEA).Through SEM,TEM,and other technologies,PPEA was characterized.In vivo,biomimetic periosteum has an apparent ability to promote nerve and bone regeneration by using Microcomputer tomography,hematoxylin-eosin,Masson,and Immunofluorescence.In vitro,Immunofluorescence,Real-Time Quantitative PCR,Alkaline phosphatase staining,and other tests were used to confirm that it has central nerve,blood vessel,and bone regeneration ability.Results: In vivo and in vitro,it has an excellent repair effect on damaged nerves and regeneration of vascular and bones.Conclusions: The PPEA biomimetic periosteum has apparent neurogenic,angiogenic,and osteogenic effects.The PPEA biomimetic periosteum will provide a promising method for treating bone defects.