title: Cell-free scaffolds with different stiffness but same microstructure promote bone regeneration in rabbit large bone defect model.
abstract: To promote bone healing, bone repair biomaterials are increasingly designed to incorporate growth factors. However, the impact of matrix mechanics of cell-free scaffold independent of microstructure on the osteogenic differentiation of endogenous osteoprogenitor cells orchestrating bone repair and regeneration remains not to be fully understood. In our recent study, three-dimensional (3D) scaffolds with different stiffness but same microstructure have been successfully fabricated by coating decellularized bone with collagen/hydroxyapatite (HA) mixture with different collagen rations. It has been demonstrated that the scaffold with optimal stiffness can induce the osteogenic differentiation of MSCs in vitro and in the subcutaneous tissue. The present in vivo study further investigated the repair efficiency of these scaffolds in a rabbit radius with a critical-sized segmental defect model and its potential mechanism. Micro-computed tomography (μ-CT), X-ray and histological analysis were carried out to evaluate the repair capacity of these scaffolds. The results demonstrated that the cell-free scaffold with optimal stiffness incorporation of endogenous osteoprogenitor cells significantly promoted the repair and reconstruction quality of mass bone defect. One of the crucial mechanisms was that hypoxia and stromal cell-derived factor-1α (SDF-1α) mediated mesenchymal stem cells (MSCs) migration by which matrix mechanics exerted influence on bone fracture healing. These findings suggested that only modulating the matrix stiffness of cell-free scaffold can be one of the most attractive strategies for promoting the progression of bone healing.
authors.affiliation: Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing, 400044, People's Republic of China.|Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing, 400044, People's Republic of China.
authors.forename: Guobao
authors.initials: G
authors.lastname: Chen
authors.affiliation: Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing, 400044, People's Republic of China.|Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing, 400044, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, Bioengineering College, Chongqing University, Chongqing, 400044, People's Republic of China.|Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing, 400044, People's Republic of China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Lv
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001861:Bone Regeneration; D018786:Bone Substitutes / Q000737:chemistry*; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000032:analysis / Q000378:metabolism; D003094:Collagen / Q000737:chemistry*; D017886:Durapatite / Q000737:chemistry; D017102:Fracture Healing; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D010012:Osteogenesis; D011817:Rabbits; D011884:Radius / Q000166:cytology / Q000293:injuries* / Q000473:pathology / Q000502:physiology*; D011885:Radius Fractures / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D018786:Bone Substitutes; D054377:Chemokine CXCL12; D003094:Collagen; D017886:Durapatite
keywords: cell recruitment; cell-free scaffold; matrix stiffness; osteogenic differentiation; radius defect model