Four-arm Polymer-Guided Formation of Curcumin-Loaded Flower-Like Porous Microspheres As Injectable Cell Carriers For Diabetic Wound Healing.

Stem cell injection is an effective approach for treating diabetic wounds; however, shear stress during injections can negatively affect their stemness and cell growth. Cell-laden porous microspheres could provide shelter for stem cells. We herein designed curcumin-loaded flower-like porous microspheres (CFPM) by combining phase inversion emulsification with thermally induced phase separation-guided four-arm poly(L-lactic acid) (B-PLLA). Notably, the CFPM showed a well-defined surface topography and inner structure, ensuring a high surface area to enable the incorporation and delivery of a large amount of stem cells and curcumin. The stem cell-carrying CFPM (BMSC@CFPM) maintained the proliferation, retention and stemness of BMSC, which, in combination with their sustainable curcumin release, facilitated the endogenous production of growth/proangiogenic factors and offered a local anti-inflammatory function. An in vivo bioluminescence assay demonstrated that BMSC@CFPM could significantly increase the retention and survival of BMSC in wound sites. Accordingly, BMSC@CFPM, with no significant systemic toxicity, could significantly accelerate diabetic wound healing by promoting angiogenesis, collagen reconstruction and M2 macrophage polarization. RNA sequencing further unveiled the mechanisms by which BMSC@CFPM promoted diabetic wound healing by increasing the expression of growth factors and enhancing angiogenesis through the JAK/STAT pathway. Overall, BMSC@CFPM represents a potential therapeutic tool for diabetic wound healing. This article is protected by copyright. All rights reserved.