Harnessing human decellularized blood vessel matrices and cellular construct implants to promote bone healing in an ex vivo organotypic bone defect model

Abstract

Decellularised matrices offer a beneficial substitute for biomimetic scaffolds in tissue engineering. The current study examines the potential of decellularised placental vessel sleeves (PVS) as a periosteal protective sleeve to enhance bone regeneration in embryonic day 18 chick femurs contained within the PVS and cultured organotypically over a 10 day period. The femurs are inserted into decellularised biocompatibility-tested PVS and maintained in an organotypic culture for a period of 10 days. In femurs containing decellularised PVS, a significant increase in bone volume (p<0.001) is evident demonstrated by micro-computed tomography (µCT) compared to femurs without PVS. Histological and immunohistological analysis revealed extensive integration of decellularised PVS with the bone periosteum, and enhanced conservation of bone architecture within the PVS. In addition the expression of Hypoxia inducible factor-1 alpha (HIF-1α), COL-II and proteoglycans were observed, indicating a possible repair mechanism via a cartilaginous stage of the bone tissue within the sleeve. The use of decellularised matrices like PVS offers a promising therapeutic strategy in surgical tissue replacement promoting biocompatibility and architecture of the tissue as well as a factor-rich niche environment with negligible immunogenicity.

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Identifiers

ORCID for Janos Kanczler: orcid.org/0000-0001-7249-0414

ORCID for Richard Oreffo: orcid.org/0000-0001-5995-6726

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