Biomimetic Supramolecular Drug Delivery Hydrogels for Accelerated Skin Tissue Regeneration.

Skin tissue is regenerated by the combinational function of skin cells, extracellular matrix (ECM), and bioactive molecules. As an artificial ECM, supramolecular hydrogels exhibited outstanding capability to mimic the physical properties of ECM. However, the lack of biochemical function in supramolecular hydrogels has limited further tissue engineering applications. Here, we developed self-assembling supramolecular drug delivery hydrogels to mimic the skin tissue regeneration process. The supramolecular hydrogels were prepared to encapsulate fibroblasts by the host-guest interaction of cyclodextrin-modified gelatin (GE-CD) and adamantane-modified hyaluronate (Ad-HA) in conjugation with human growth hormone (hGH) for accelerated skin tissue regeneration. In vitro, GE-CD/Ad-HA-hGH hydrogels showed highly facilitated cell growth by the controlled hGH delivery. After a subcutaneous injection into the back of mice, IVIS imaging of bioengineered fibroblasts to express red fluorescence protein (RFP) revealed prolonged cell survival and proliferation in the supramolecular hydrogels for more than 21 days. We could also observe the improved skin tissue regeneration by the facilitated fibroblast proliferation with angiogenesis. Taken together, we could confirm the feasibility of biomimetic supramolecular drug delivery GE-CD/Ad-HA-hGH hydrogels for various tissue engineering applications.