(B-44) Enhancing wound healing quality using biomacromolecular granular hydrogel scaffolds

Introduction:: Scaffold-based wound healing therapies have enabled significant improvement in the rate and quality of healing. To further improve these therapies, hydrogel microparticle (HMP) have been fabricated as building blocks and assembled into granular hydrogel scaffolds (GHS), facilitating cell ingrowth and reducing inflammation. Despite the extensive use of bulk gelatin methacryloyl (GelMA) hydrogel scaffolds for wound healing, the potential of GelMA GHS for this purpose remains vastly unknown.


Materials and Methods:: GHS was formed by photocrosslinking GelMA HMP with a size of 86 ± 3 µm (large) or 30 ± 1 µm (small), and mechanical characterizations were conducted on them (Fig. 1a). The median pore equivalent diameter and void fraction were analyzed via fluorescence microscopy, and the compressive modulus of GHS was measured using an Instron mechanical tester (Fig. 1b). The effect of GHS porosity on macrophage behavior was compared with bulk (non-porous) GelMA scaffolds. A murine model of full-thickness skin injury was used to assess the effect of porosity on wound healing in vivo.

Results, Conclusions, and Discussions:: The median pore equivalent diameter of large and small GelMA GHS is 16 ± 1 µm and 10 ± 1 µm, respectively. The compressive modulus was decreased by increasing the HMP size (Fig. 1c). Thus, the GHS with large HMP, resembling the native skeletal muscle tissue was selected for in vitro and in vivo characterizations. The immune response to the GHS was further evaluated in vitro using bone marrow derived macrophages (BMDMs). Based on the Enzyme-linked immunosorbent assay (ELISA), the pro-inflammatory IFN-γ cytokine was decreased and the immunomodulatory IL-10 cytokine was increased in GHS compared with the bulk scaffold (Fig. 1d). Although the rate of in vivo wound closure was not affected by porosity, hematoxylin and eosin (H&E) staining and immunofluorescence staining 11 days post-implantation showed a thicker granulation tissue, which attested to an improved wound healing quality using GelMA GHS (Fig. 1e). In vitro and in vivo results consistently show that GelMA GHS better supports tissue regeneration than the bulk counterpart. This study lays the foundation for engineering regenerative GelMA GHS.


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