Four-Arm Polymer-Guided Formation of Curcumin-Loaded Flower-Like Porous Microspheres as Injectable Cell Carriers for Diabetic Wound Healing.

Abstract

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 canprovide shelter for bone mesenchymal stem cells (BMSC). Herein, curcumin-loaded flower-like porous microspheres (CFPM) are designed by combining phase inversion emulsification with thermally induced phase separation-guided four-arm poly (l-lactic acid) (B-PLLA). Notably, the CFPM shows a well-defined surface topography and inner structure, ensuring a high surface area to enable the incorporation and delivery of a large amount of -BMSC and curcumin. The BMSC-carrying CFPM (BMSC@CFPM) maintains the proliferation, retention, and stemness of -BMSCs, which, in combination with their sustainable curcumin release, facilitates the endogenous production of growth/proangiogenic factors and offers a local anti-inflammatory function. An in vivobioluminescence assay demonstrates that BMSC@CFPM cansignificantly increase the retention and survival of BMSC in wound sites. Accordingly, BMSC@CFPM, with no significant systemic toxicity, couldsignificantly accelerate diabetic wound healing by promoting angiogenesis, collagen reconstruction, and M2 macrophage polarization. RNA sequencing further unveils the mechanisms by which BMSC@CFPM promotes diabetic wound healing by increasing -growth factors and enhancing angiogenesis through the JAK/STAT pathway. Overall, BMSC@CFPM represents a potential therapeutic tool for diabetic wound healing.