Fabrication And Mechanism Study Of An Engineered Small Intestinal Submucosa Scaffolds For Bone Repair

Objective: The treatment of large bone defects,such as disease and external trauma,needs to be treated by bone graft.In recent years,the rapid development of tissue engineering bone provides a new way to solve this problem.Decellularized small intestinal submucosa has been broadly applied in tissue engineering in vitro and in vivo.In this study,our aim was to study the osteogenic capacity of SIS-based scaffold for different types of bone defect.Methods:(1)The effect of SIS scaffolds on cell attachment,cell proliferation,cell differentiation were examined in vitro.A mouse calvarial defect model to assess new bone formation and to investigate the mechanism in this process in vivo.(2)SIS/PMMA specimens were characterized by morphology,compressive modulus and compressive strength.The cell responses to composites were studied in vitro.SD rat was used in a vertebral defect model to assess osteointegration and new bone formation.(3)Osteoblasts-derived extracellular matrix was used to coating SIS,cell adhesion,proliferation and osteogenic differentiation of ADSCs on ECM-SIS were evaluated in vitro.A mouse calvarial defect model was used to assess effects on bone regeneration in vivo.Results:(1)SIS scaffold was beneficial for cell attachment,proliferation,migration and osteogenic differentiation of various cells contributing to bone repair.In mouse calvarial defect model,bone regeneration was significantly enhanced in the defects implanted with SIS scaffolds,along with the activation of BMP-SMAD pathway.(2)SIS/PMMA has a porous three-dimensional structure with lower compressive strength and compressive modulus.Cytocompatibility of the SIS/PMMA composite was enhanced in vitro.In a vertebral defect model,the SIS/PMMA composite greatly enhanced osteointegration,tissue union and bone regeneration.(3)Abundant ECM was coated on SIS,which facilitated cell adhesion,proliferation and osteogenic differentiation of ADSCs.Bone regeneration in vivowas enhanced by ECM-SIS + ADSCs via BMP/SMAD pathway.Conclusion: SIS is a potential osteoconductive and osteoinductive biomaterial for bone tissue engineering,which can be used as a clinical additive of PMMA cement to vertebral body repair.Meanwhile,we developed a bone matrix modified SIS composite scaffold,which can synergy with stem cells to enhance the effect of bone repair in vivo.