Plasma-polymerized pericyte patches improve healing of murine wounds through increased angiogenesis and reduced inflammation

Pericytes have the potential to be developed as a cell therapy for the treatment of wounds; however, the efficacy of any cell therapy relies on the successful delivery of intact and functioning cells. Here, the effect of delivering pericytes on wound repair was assessed alongside the development of a surface-functionalized pericyte patch. Plasma polymerization (PP) was used to functionalize the surface of silicone patches with heptylamine (HA) or acrylic acid (AA) monomers. Human pericytes were subsequently delivered to murine excisional wounds by intradermal injection or using the pericyte-laden patches and the comparative effects on wound healing, inflammation and revascularization determined. The AA surface provided the superior transfer of the cells to de-epidermized dermis. Excisional murine wounds treated either with pericytes injected directly into the wound or with the pericyte-laden AA patches showed improved healing with decreased neutrophil infiltration and reduced numbers of macrophages in the wounds. Pericyte delivery also enhanced angiogenesis through a mechanism independent of VEGF signalling. Pericytes, when delivered to wounds, improved healing responses by dampening inflammation and promoting angiogenesis. Delivery of pericytes using PP-AA-functionalized patches was equally as effective as direct injection of pericytes into wounds. Pericyte-functionalized dressings may therefore be a clinically relevant approach for the treatment of wounds.Hannah M. Thomas, Parinaz Ahangar, Robert Fitridge, Giles T.S. Kirby, Stuart J. Mills and Allison J. Cowi

Microparticles for sustained growth factor delivery in the regeneration of critically-sized segmental tibial bone defects

The Publisher's final version can be found by following the DOI link. Open access article.This study trialled the controlled delivery of growth factors within a biodegradable scaffold in a large segmental bone defect model. We hypothesised that co-delivery of vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) followed by bone morphogenetic protein-2 (BMP-2) could be more effective in stimulating bone repair than the delivery of BMP-2 alone. Poly(lactic-co-glycolic acid) (PLGA ) based microparticles were used as a delivery system to achieve a controlled release of growth factors within a medical-grade Polycaprolactone (PCL) scaffold. The scaffolds were assessed in a well-established preclinical ovine tibial segmental defect measuring 3 cm. After six months, mechanical properties and bone tissue regeneration were assessed. Mineralised bone bridging of the defect was enhanced in growth factor treated groups. The inclusion of VEGF and PDGF (with BMP-2) had no significant effect on the amount of bone regeneration at the six-month time point in comparison to BMP-2 alone. However, regions treated with VEGF and PDGF showed increased vascularity. This study demonstrates an effective method for the controlled delivery of therapeutic growth factors in vivo, using microparticles