Injectable Mussel-Inspired Immobilization of Platelet-Rich Plasma on Microspheres Bridging Adipose Micro-Tissues to Improve Autologous Fat Transplantation by Controlling Release of PDGF and VEGF, Angiogenesis, Stem Cell Migration.

Abstract

Platelets-rich plasma (PRP) can produce growth factors (GFs) to improve angiogenesis. However, direct injection of PRP does not lead to highly localized GFs. The current study employs a mussel-inspired polydopamine to immobilize PRP on gelatin microspheres (GMs) with the purpose of bridging adipose micro-tissues to help implanted fat survive (GM-pDA-PRP). Enhanced PRP adhesion leads to a prolonged and localized production of GFs, which is verified by platelet counting and by ELISA of vascular endothelial growth factors (VEGFs) and of platelet derived growth factors (PDGFs). The GM-pDA-PRP "hatches" a microenvironment for the proliferation of adipose-derived stem cells. After the adipose micro-tissue has bridged with GM-pDA-PRP after 16 weeks, triple-fluorescence staining reveals that the mature adipocytes, blood vessels, and capillaries are arranged like in normal adipose tissue. The survival fat increases significantly compared to that in control, PRP, and GM-PRP groups (84.8 ± 11.4% versus 47.8 ± 8.9%, 56.9 ± 9.7%, and 60.2 ± 10.5%, respectively). Both histological assessments and CD31 immunofluorescence indicate that the improvement of angiogenesis in GM-pDA-PRP is higher than in the fat graft group (6.4-fold in quantitative CD31 positive cells). The CD34 positive cells in the GM-pDA-PRP group are around 3.5-fold the amount in the fat graft group, which suggests that more stem cells migrate to the implant area. Cell proliferation staining shows that the number of Ki67 positive cells is around five times as high as that in the fat graft group.