Generation of a PLLA Scaffold Functionalised with Mesenchymal Cells and Microvascular Fragments for Chronic Wound Regeneration

Chronic wounds are challenging due to impaired cellular activity, reduced vascularization, and high infection risk. We developed a three- dimensional tissue-engineered construct using PLLA scaffolds seeded with dermal fibroblasts (RDFs) and adipose-derived microvascular fragments (MVFs) to support cell colonization and vascular network formation in a preclinical rat model. Fibroblasts adhered, proliferated, and deposited extracellular matrix, while MVFs retained angiogenic potential, forming lumenized, interconnected vascular networks stabilized by scaffold biofunctionalization and VEGF supplementation. Co-culture generated dense, pre-vascularized constructs, demonstrating synergistic interactions that recapitulate native tissue features. Translational studies with human dermal fibroblasts confirmed effective adhesion, proliferation, and matrix remodeling on the scaffolds, with coated surfaces enhancing early cellular integration and extracellular matrix formation. These findings highlight a robust platform for generating functional, vascularized tissue constructs that could support chronic wound repair in both preclinical and human contexts.