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

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.