Fabrication of a bio-instructive scaffold conferred with a favorable microenvironment allowing for superior implant osseointegration and accelerated in situ vascularized bone regeneration via type H vessel formation

Abstract

The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone, most likely resulted from the inability to replicate appropriate endogenous crosstalk between cells. Human umbilical vein endothelial cell-derived decellularized extracellular matrix (HdECM), which contains a collection of angiocrine biomolecules, has recently been demonstrated to mediate endothelial cells(ECs) – osteoprogenitors(OPs) crosstalk. We employed the HdECM to create a PCL (polycaprolactone)/fibrin/HdECM (PFE) hybrid scaffold. We hypothesized PFE scaffold could reconstitute a bio-instructive microenvironment that reintroduces the crosstalk, resulting in vascularized bone regeneration. Following implantation in a rat femoral bone defect, the PFE scaffold demonstrated early vascular infiltration and enhanced bone regeneration by microangiography (μ-AG) and micro-computational tomography (μ-CT). Based on the immunofluorescence studies, PFE mediated the endogenous angiogenesis and osteogenesis with a substantial number of type H vessels and osteoprogenitors. In addition, superior osseointegration was observed by a direct host bone-PCL interface, which was likely attributed to the formation of type H vessels. The bio-instructive microenvironment created by our innovative PFE scaffold made possible superior osseointegration and type H vessel-related bone regeneration. It could become an alternative solution of improving the osseointegration of bone substitutes with the help of induced type H vessels, which could compensate for the inherent biological inertness of synthetic polymers.

A Comprehensive Review on Collagen Type I Development of Biomaterials for Tissue Engineering: From Biosynthesis to Bioscaffold

“…Decellularized extracellular matrix hydrogels, which may or may not contain cells, can be used as printing inks for three-dimensional bioprinting [ 245 , 246 , 247 ]. Other decellularization processes include decellularizing cornea to fabricate improved constructs [ 248 ], decellularizing human-umbilical-vein-endothelial-cell (HUVEC)-derived extracellular matrix to be integrated into a manufactured scaffold with collagen type I to improve endothelial cells with progenitor cell crosstalk due to their intact angiocrine biomolecules for osseointegration [ 249 ], and decellularizing rat livers to form acellular 3D bioscaffolds suitable for seeding with induced pluripotent stem cells (iPSCs) [ 250 ]. The focus of research may vary depending on the technology and application, but the fundamental use of collagen type I is undeniable.…”

3D bioprinting of dECM/Gel/QCS/nHAp hybrid scaffolds laden with mesenchymal stem cell-derived exosomes to improve angiogenesis and osteogenesis

“…Culture in a 3D bioprinted scaffold with unique nanostructures and enhanced further the proliferation of hBMSCs in the dGQH 20 @Exo group in comparison to all other groups. Therefore, the beneficial physical structure and bioactive factors are both required to foster an angiogenic-osteogenic microenvironment for accelerating bone regeneration [90].…”

Recent Advances in Decellularized Matrix-Derived Materials for Bioink and 3D Bioprinting

“…Endothelial cell dECMs promote angiogenesis in the bone microenvironment. In vivo research revealed the importance of vascular infiltration and bone regeneration using a hybrid PCL/fibronectin/dECM scaffold (PFE) made from HUVEC-derived dECMs (HdECM), demonstrating that the environmental signals in the dECM could induce angiogenesis and osteogenesis [ 97 ].…”