Collagen–Hyaluronic Acid Composite Hydrogels with Applications for Chronic Diabetic Wound Repair

Abstract

Chronic diabetic wounds have become a major healthcare challenge worldwide. Improper treatment may lead to serious complications. Current treatment methods including biological and physical methods and skin grafting have limitations and disadvantages, such as poor efficacy, inconvenience of use, and high cost. Therefore, developing a more effective and feasible treatment is of great significance for the repair of chronic diabetic wounds. Hydrogels can be designed to serve multiple functions to promote the repair of chronic diabetic wounds. Furthermore, 3D bioprinting enables hydrogel customization to fit chronic diabetic wounds, thus facilitating the healing process. This paper reports a study of 3D printing of a collagen−hyaluronic acid composite hydrogels with application for chronic diabetic wound repair. In situ printed hydrogels were developed by a macromolecular crosslinking network using methacrylated recombinant human collagen (RHCMA) and methacrylated hyaluronic acid (HAMA), both of which can respond to ultraviolet (UV) irradiation. The hydrogels were also loaded with silver nanoclusters (AgNCs) with ultra-small-size nanoparticles, which have the advantages of deep penetration ability and broad-spectrum high-efficiency antibacterial properties. The results of this study show that the developed RHCMA, HAMA, and AgNCs (RHAg) composite hydrogels present good UV responsiveness, porosity, mechanical properties, printability, and biocompatibility, all of which are beneficial to wound healing. The results of this study further show that the developed RHAg hydrogels not only effectively inhibited Staphylococcus aureus and Pseudomonas aeruginosa but also promoted the proliferation and migration of fibroblasts in vitro and tissue regeneration and collagen deposition in vivo, thus producing a desirable wound repair effect and can be used as an effective functional biomaterial to promote chronic diabetic wound repair.

Neuro-Inspired Biomimetic Microreactor for Sensory Recovery and Hair Follicle Neogenesis under Skin Burns

“…For Neuro-MOF microreactors to be applied more appropriately and under realistic conditions for the burn wounds, they were packed into the cross-linkable HAMA hydrogels (called HAMA + Neuro-MOF). The essence of HAMA hydrogel is hyaluronic acid esterified by methacrylate, which is favored in medical applications because of its good biocompatibility, biodegradability, and low immunogenicity. , The HAMA hydrogel is an ultraviolet (UV) cross-linked biodegradable hydrogel. − We used UV irradiation to cure the HAMA hydrogel, with particular attention to its adverse effects on wound tissue. We used a low-dose and range-restricted approach to confine UV irradiation to the hydrogel area, minimizing its impact on deep and out-of-range tissues.…”

Bioarchitectural Design of Bioactive Biopolymers: Structure–Function Paradigm for Diabetic Wound Healing

“…Recently, 3D bioprinting methods have been employed to create HA-collagen composites (MW 100-200 kDa) incorporated with silver nanoclusters for addressing chronic diabetic wounds. These hydrogels have demonstrated the ability to stimulate fibroblast proliferation and migration, while also augmenting collagen deposition, as evidenced by both in vitro and in vivo investigations [187]. MW dependency is also reported on wound healing outcomes.…”

“…Consequently, modifications to collagen structure can be strategically employed to direct cellular responses. Its hydrophilic nature makes it possible to blend with other natural (dextran [198], chitosan [199], alginate [200], HA [187]), and synthetic polymers (polyacrylamide [201], polyvinyl alcohol [202]) to make stable formulations. Collagen, considered to be a 'self' molecule, is immunologically accepted by the human body and is also highly biocompatible and biodegradable by endogenous collagenases.…”