Cord Blood Platelet-Poor Plasma Functionalizes Polycaprolactone Scaffolds for Coupled Vascularization and Osteogenesis in Bone Tissue Engineering.

Abstract

Background: Angiogenesis is critical for the success of 3D scaffolds in bone tissue engineering. This study investigated the use of platelet-poor plasma (PPP) derived from umbilical cord blood (UCB) as a bioactive coating agent to impart osteo-inductive, angiogenic, and immunomodulatory properties to 3D-printed polycaprolactone (PCL) scaffolds.

Methods: PCL scaffolds were coated with UCB-PPP and evaluated in vitro for cell adhesion, proliferation, extracellular matrix (ECM) expression, and osteogenic differentiation of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and fibroblasts (hFBs). In vitro angiogenesis was evaluated via the tube formation of human umbilical vein-derived endothelial cells. In vivo neovascularization and tissue integration were assessed using a subcutaneous mouse implantation model, alongside immunogenicity testing using rat and human allogeneic mononuclear cells.

Results: The PPP coating proved highly effective, enhancing adhesion and proliferation of hUC-MSCs and hFBs by upregulating ECM components and pro-regenerative cytokines. In vitro, PPP coating promoted osteoblast differentiation of hUC-MSCs, as evidenced by increased calcium deposition and expression of osteoprogenitor markers. Crucially, the PPP coating stimulated robust in vitro tube formation and in vivo subcutaneous neovascularization, evidenced by functional, erythrocyte-perfused endothelial lumens, elevated VEGF-A expression, and M2 macrophage polarization. Moreover, PPP-coated scaffolds demonstrated low immunogenicity in both rat and human allogeneic mononuclear cells, thereby supporting preclinical safety and immunomodulation.

Conclusions: UCB-PPP serves as an immune-tolerant, highly bioactive coating that functionalizes inert PCL scaffolds by promoting in vitro osteogenesis and in vivo functional vascular integration. This dual-action strategy provides a promising proof-of-concept for addressing vascularization bottlenecks in bone tissue engineering applications.