Bilayer micropatterned hydrogel scaffolds loaded with ADSCs improved integration with regenerated tissue and diabetic wound healing

[Display omitted] •Micropatterned hydrogel scaffold (MPS) loaded with ADSC (ADSC@MPS) was fabricated.•The unified bilayer MPS mimicked epidermis/dermis structure of skin.•MPS integrated well with the granulation tissue of diabetic wounds.•ADSC@MPS promoted angiogenesis and neuronal differentiation.•ADSC@MPS improved collagen deposition and diabetic wound healing. Adipose-derived stem cells (ADSCs) have great potential to improve diabetic wound (DW) healing. However, their low cellular retention rate compromises their performance. Here, a bilayer skin-mimicking micropatterned hydrogel scaffold (MPS) loaded with human ADSCs (hADSC@MPS) was developed. In the MPS, the gelatin hydrogel micropattern was well embedded into the crosslinked gelatin electrospun membrane, forming a unified structure. The micropattern was composed of cylindrical hydrogels with a diameter of 511 ± 10 μm and center distance of 801 ± 13 μm, while the fiber diameter of the membrane was 1346 ± 292 nm. In collagenase solution, the micropattern was completely degraded within 15 h, while the membrane degraded in one week. To prepare hADSC@MPS, hADSCs were first adhered on the membrane, onto which a hydrogel micropattern was prepared. The hADSCs showed a high activity; the significantly different degradation rates of the membrane and micropattern may facilitate the retention of the hADSCs in DWs. After being applied to a DW, gross observation and optical coherence tomography-based in situ scanning showed that the MPS integrated well with the wounds. The hADSCs@MPS promoted granulation regeneration, re-epithelialization, collagen deposition, and neuronal differentiation. The MPS degraded at a suitable rate that allowed the hADSCs to modulate macrophage polarization and enhance angiogenesis to synergistically improve DW healing.