Biomimetic Supramolecular Drug Delivery Hydrogels for Accelerated Skin Tissue Regeneration

Abstract

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.

Supramolecular Hydrogels for Precisely Controlled Antimicrobial Peptide Delivery for Diabetic Wound Healing

“…Since the beginning of clinical applications of protein and peptide drugs, there have been extensive research efforts to extend their short half-lives in the body. , Among them, PEGylation technology has attracted great attention to protect protein and peptide drugs from degradation and rapid clearance. − However, PEGylation suffered from nonbiodegradability, accelerated blood clearance by repeated injections, and immune responses. As an alternative, HA conjugation has been proposed for target-specific and long-acting protein and peptide drug delivery. , In this work, we used supramolecular HA hydrogels for smart delivery of AMP in response to the bacterial infection. For the Ad–HA–AMP synthesis, Ad–HA was modified with 52 ± 1 mol % aldehyde as reported elsewhere .…”

“…The sHGs exhibited shear thinning and injectability with biodegradability. In addition, the sHGs prevented the uncontrolled initial burst release of tethered drugs due to the supramolecular interaction between the hydrogels and conjugated drugs . It is expected that the sHGs would be transplanted in a minimally invasive manner with good integration to the wound site as a controlled drug-delivery carrier.…”

“…Ad–HA–AMP was synthesized by the aldehyde–amine reaction between Ad–HA–ald and AMP . First, the aldehyde motif was introduced to Ad–HA by using sodium periodate.…”

Biomimetic Biomaterials Based on Polysaccharides: Recent Progress and Future Perspectives

“…This idea was applied in a recent investigation related to the preparation of supramolecular hydrogels that mimicked the properties of the extracellular matrix via the interactions between cyclodextrin‐modified gelatin and adamantane‐modified hyaluronate. [ 191 ] In vivo essays demonstrated a good survival and proliferation of fibroblasts for more than 21 d and accelerated skin tissue regeneration. A biomimetic mineralization ability was observed for heterojunctions containing nanohydroxyapatite, carboxymethyl chitosan, and β ‐CD fused with date seed extract, which improved bone tissues regeneration.…”

Biomimetic Extracellular Scaffolds by Microfluidic Superstructuring of Nanofibers

“…The extracellular matrix (ECM) is a masterwork of biology that provides mechanical support and biological signals according to each tissue’s specific needs. − Among many other functions, it mediates biochemical signaling pathways, supports and directs cell growth, and remodels its chemistry and microstructure in response to cellular activity . Although many different biomaterials have been suggested as mimics for ECM, the chemical versatility, morphologic adaptability, and biodegradability of nanoscopic supramolecular biomaterials represent an exceptionally promising option. − …”