Construction of Smart Biomaterials for Promoting Diabetic Wound Healing

Abstract

Diabetes mellitus is a complicated metabolic disease that has become one of the fastest-growing health crises in modern society. Diabetic patients may suffer from various complications, and diabetic foot is one of them. It can lead to increased rates of lower-extremity amputation and mortality, even seriously threatening the life and health of patients. Because its healing process is affected by various factors, its management and treatment are very challenging. To address these problems, smart biomaterials have been developed to expedite diabetic wound closure and improve treatment outcomes. This review begins with a discussion of the basic mechanisms of wound recovery and the limitations of current dressings used for diabetic wound healing. Then, the categories and characteristics of the smart biomaterial scaffolds, which can be utilized as a delivery system for drugs with anti-inflammatory activity, bioactive agency, and antibacterial nanoparticles for diabetic wound treatment were described. In addition, it can act as a responsive system to the stimulus of the pH, reactive oxygen species, and glucose concentration from the wound microenvironment. These results show that smart biomaterials have an enormous perspective for the treatment of diabetic wounds in all stages of healing. Finally, the advantages of the construction of smart biomaterials are summarized, and possible new strategies for the clinical management of diabetic wounds are proposed.

Keywords: biological dressings; diabetic foot; hydrogel; regenerative medicine; tissue engineering; wound healing.

Figure 1

Four overlapping but distinct stages of wound repair healing: hemostasis, inflammation, epidermal regeneration, and scar maturation. Reproduced with permission from Ref. [7]. Published by The Royal Society, 2020.

Figure 2

Factors affecting diabetic wound healing, including hyperglycemia, neuropathy, microvascular complications, and infection.

Figure 3

(A): Here, CNPs@GMs were obtained by loading CNPs into GMs, and CNPs@GMs were mixed with thermosensitive hydrogel and covered on the wounds of diabetic mice. Reproduced with permission from Ref. [73]. Published by ACS Publications, 2018. (B): Inflammatory-responsive drug hydrogels were synthesized after encapsulation with vancomycin-conjugated silver nanoclusters (VAN-AgNCs) and nimesulide (NIM)-loaded pH-sensitive micelles for promoting the healing of infected wounds. Reproduced with permission from Ref. [74]. Published by ACS Publications, 2021.

Figure 4

Summary of the key role of bio-intelligent materials in delivering growth factors in healing.

Figure 5

The application of smart biomaterials loaded with nanoparticles in diabetic wound healing.

Figure 6

GelDerm is a multifunctional dressing for wound monitoring and management. When skin is damaged, the acidic environment can be disturbed. GelDerm is capable of colorimetric pH measurements, connects to an internal smartphone app (iDerm), records a digital image of the GelDerm, reports the pH, and releases antibiotics into the wound site. Reproduced with permission from Ref. [91]. Published by Wiley, 2017.