Vascular restoration through local delivery of angiogenic factors stimulates bone regeneration in critical size defects

Critical size bone defects represent a significant challenge worldwide,often leading to persistent pain and physical disability that profoundly impact patients’quality of life and mental well-being.To address the intricate and complex repair processes involved in these defects,we performed single-cell RNA sequencing and revealed notable shifts in cellular populations within regenerative tissue.Specifically,we observed a decrease in progenitor lineage cells and endothelial cells,coupled with an increase in fibrotic lineage cells and pro-inflammatory cells within regenerative tissue.Furthermore,our analysis of differentially expressed genes and associated signaling pathway at the single-cell level highlighted impaired angiogenesis as a central pathway in critical size bone defects,notably influenced by reduction of Spp1 and Cxcl12 expression.This deficiency was particularly pronounced in progenitor lineage cells and myeloid lineage cells,underscoring its significance in the regeneration process.In response to these findings,we developed an innovative approach to enhance bone regeneration in critical size bone defects.Our fabrication process involves the integration of electrospun PCL fibers with electrosprayed PLGA microspheres carrying Spp1 and Cxcl12.This design allows for the gradual release of Spp1 and Cxcl12 in vitro and in vivo.To evaluate the efficacy of our approach,we locally applied PCL scaffolds loaded with Spp1 and Cxcl12 in a murine model of critical size bone defects.Our results demonstrated restored angiogenesis,accelerated bone regeneration,alleviated pain responses and improved mobility in treated mice.

Carboxymethyl chitosan-alginate enhances bone repair effects of magnesium phosphate bone cement by activating the FAK-Wnt pathway

There is a continuing need for artificial bone substitutes for bone repair and reconstruction,Magnesium phosphate bone cement(MPC)has exceptional degradable properties and exhibits promising biocompatibility.However,its mechanical strength needs improved and its low osteo-inductive potential limits its therapeutic application in bone regeneration.We functionally modified MPC by using a polymeric carboxymethyl chitosan-sodium alginate(CMCS/SA)gel network.This had the advantages of:improved compressive strength,ease of handling,and an optimized interface for bioactive bone in-growth.The new composites with 2%CMCS/SA showed the most favorable physicochemical properties,including mechanical strength,wash-out resistance,setting time,injectable time and heat release.Biologically,the composite promoted the attachment and proliferation of osteoblast cells.It was also found to induce osteogenic differentiation in vitro,as verified by expression of osteogenic markers.In terms of molecular mechanisms,data showed that new bone cement activated the Wnt pathway through inhibition of the phosphorylation ofβ-catenin,which is dependent on focal adhesion kinase.Through micro-computed tomography and histological analysis,we found that the MPC-CMCS/SA scaffolds,compared with MPC alone,showed increased bone regeneration in a rat calvarial defect model.Overall,our study suggested that the novel composite had potential to help repair critical bone defects in clinical practice.