4.6 Article

Functionalized Decellularized Bone Matrix Promotes Bone Regeneration by Releasing Osteogenic Peptides

Journal

ACS BIOMATERIALS SCIENCE & ENGINEERING
Volume 9, Issue 8, Pages 4953-4968

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.3c00413

Keywords

decellularized bone matrix; osteogenic peptide; Smad; Runx2 pathway; osteogenic differentiation; bone regeneration

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In this study, a functionalized decellularized bone scaffold was developed by incorporating peptides derived from bone morphogenetic protein-2, which enhanced osteogenesis and showed great potential for the treatment of large bone defects.
The decellularized bone matrix (DCB) provides a promisingbonesubstitute for the treatment of bone defects because of its similarbiochemical, biophysical, and mechanical properties to normal bonetissue. However, the decellularized procedure also greatly reducedits osteogenic induction activity. In this study, peptides derivedfrom the knuckle epitope of bone morphogenetic protein-2 were incorporatedinto the thermo-sensitive hydrogel poloxamer 407, and the peptide-loadedhydrogel was then filled into the pores of DCB to construct a functionalizedscaffold with enhanced osteogenesis. In vitro studies have shown thatthe functionalized DCB scaffold possessed appropriate mechanical propertiesand biocompatibility and exhibited a sustained release profile ofosteogenic peptide. These performances critically facilitated cellproliferation and cell spreading of bone marrow mesenchymal stem cellsand upregulated the expression of osteogenic-related genes by activatingthe Smad/Runx2 signaling pathway, thereby promoting osteogenic differentiationand extracellular matrix mineralization. Further in vivo studies demonstratedthat the functionalized DCB scaffold accelerated the repair of criticalradial defects in rabbits without inducing excessive graft-relatedinflammatory responses. These results suggest a clinically meaningfulstrategy for the treatment of large segmental bone defects, and theprepared osteogenic peptide modified composite DCB scaffold has greatapplication potential for bone regeneration.

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