Hypoxic ADSC-CM-Loaded Separable Bilayer Micropatterned Dressing Improved Diabetic Wound Healing via Tissue Integration and Immune Modulation

Dressings loaded with bioactive factors secreted by adipose-derived stem cells (ADSCs) show potential for diabetic wound healing. However, single functionality and limited integration with wounds hinder their efficacy. Hence, a bilayer micropattern dressing (BMPD) consisting of micropatterned scaffold G5A0.4-MP and an antiadhesion PDMS/A1 layer is prepared. G5A0.4-MP facilitates tissue integration, while the PDMS/A1 layer protects wounds and prevents adhesion. G5A0.4-MP is cross-linked through a photomask, resulting in cylindrical hydrogels with a diameter of 387.4 ± 27.2 μm and a thickness of 417.8 ± 32.3 μm. The swelling ratios of these two layers are significantly different, which allows the detachment of G5A0.4-MP from the PDMS/A1 layer to integrate well with the granulation tissue after lyophilized BMPDs are applied onto wounds. BMPDs with different micropattern interspaces are obtained by changing photomasks, among which the one with an interspace of 100 μm (BMPD-100) shows the best effect on improving wound healing. Hence, a hypoxic ADSC-conditioned medium is loaded into G5A0.4-MP to obtain CM@BMPD-100. CM@BMPD-100 enriches MMP-9 into the micropatterned hydrogel and downregulates the corresponding content in granulation tissue. Additionally, it promotes cell proliferation, regulates the polarization of macrophages from M1 type to M2 type, and enhances vascularization and collagen deposition, and it has been shown to promote diabetic wound healing.