Growth plate extracellular matrix-derived scaffolds for large bone defect healing

Abstract

Limitations associated with demineralised bone matrix and other grafting materials have motivated the development of alternative strategies to enhance the repair of large bone defects. The growth plate (GP) of developing limbs contain a plethora of growth factors and matrix cues which contribute to long bone growth, suggesting that biomaterials derived from its extracellular matrix (ECM) may be uniquely suited to promoting bone regeneration. The goal of this study was to generate porous scaffolds from decellularised GP ECM and to evaluate their ability to enhance host mediated bone regeneration following their implantation into critically-sized rat cranial defects. The scaffolds were first assessed by culturing with primary human macrophages, which demonstrated that decellularisation resulted in reduced IL-1β and IL-8 production. In vitro, GP derived scaffolds were found capable of supporting osteogenesis of mesenchymal stem cells via either an intramembranous or an endochondral pathway, demonstrating the intrinsic osteoinductivity of the biomaterial. Furthermore, upon implantation into cranial defects, GP derived scaffolds were observed to accelerate vessel in-growth, mineralisation and de novo bone formation. These results support the use of decellularised GP ECM as a scaffold for large bone defect regeneration.

Endochondral bone regeneration: Stepping stones towards clinical translation

“…Evidence supporting the feasibility of using devitalized native cartilage for endochondral bone regeneration (EBR) has been available since 1920, when Asami and Dock [409] implanted boiled ear and xiphoid cartilage subcutaneously in a rabbit and observed new bone formation. Recent studies further confirmed the feasibility of using decellularized or devitalized cartilaginous templates to trigger EBR ectopically [66,95,[103][104][105] and orthotopically in rodents [95,104,114,410]. Nevertheless, unsatisfactory results in terms of bone regeneration were observed when the decellularized or devitalized cartilaginous constructs were compared to the respective living control [104,105,114].…”