Injectable Pectin–Alginate Hydrogels for Improving Vascularization and Adipogenesis of Human Fat Graft

Abstract

Autologous fat grafting (AFG) is the most prevailing tool for soft tissue regeneration in clinics, although efficiency is limited to unpredictable volume resorption due to poor vascularization and eventual necrosis. This study sought to improve the AFG efficiency using a hydrogel as a carrier for human fat graft (F) with and without platelet-rich plasma (PRP). PRP is clinically well known for the local release of several endogenous growth factors and has been in clinical use already. A human-fat-graft-encapsulated pectin–alginate hydrogel (FG) was developed and characterized. PRP was added to F to develop a human fat graft with PRP (FP). FP was admixed with a pectin–alginate hydrogel to develop FGP. FG and FGP showed the smooth injectable, elastic, and shear-thinning properties. FG and FGP groups showed enhanced cell viability and proliferation compared to the control F in vitro. We also investigated the in vivo angiogenesis and neo-adipogenesis ability of F, FG, FGP, and FP in nude mice after subcutaneous injection. After 2 and 4 weeks, an MRI of the mice was conducted, followed by graft explantation. The explanted grafts were also assessed histologically and with immunohistochemistry (IHC) studies. MRI and histology results revealed better vascularity of the FG and FGP system compared to fat graft alone. Further, the IHC studies, CD 31, and perilipin staining also revealed better vasculature and adipogenesis of FG and FGP systems. These results indicate the enhanced angiogenesis and adipogenesis of FG and FGP. Thus, developed pectin–alginate hydrogel-based fat graft systems FG and FGP replenish the native microenvironment by mediating angiogenesis and adipogenesis, thereby maximizing the clinical outcomes of autologous fat grafting.

Engineering 3D-Printed Bioresorbable Scaffold to Improve Non-Vascularized Fat Grafting: A Proof-of-Concept Study

“…Third, several tissue engineering strategies have been developed to enhance fat graft survival and therefore allow for the maintenance of tissue volume. These include the use of natural biomaterials [35] and/or growth factors [36]. Although very attractive, these approaches are often difficult to integrate into clinical practice due to regulatory constraints and potential risk.…”

Harnessing extracellular vesicles-mediated signaling for enhanced bone regeneration: novel insights into scaffold design

“…The findings presented in figure 8 offer empirical evidence of the IPN scaffolds' enhanced ability to stimulate vascularization compared to controls, marking a significant step forward in improving artificial bone grafts and advancing bone tissue engineering. Janarthanan et al previously demonstrated pectin's significant effects on endothelial cells, promoting vascularization [94]. Flournoy et al's research further underscores the role of mechanobiological factors, like substrate stiffness and geometry, in regulating angiogenesis [95].…”