Biomimetic Glycopolypeptide Hydrogels with Tunable Adhesion and Microporous Structure for Fast Hemostasis and Highly Efficient Wound Healing

Abstract

Despite clinical applications of the first‐generation tissue adhesives and hemostats, the correlation among microstructure and hemostasis of hydrogels with wound healing is less understood and it is elusive to design high‐performance hydrogels to meet worldwide growing demands in wound closure, hemostasis, and healing. Inspired by the microstructure of extracellular matrix and mussel‐mimetic chemistry, two kinds of coordinated and covalent glycopolypeptide hydrogels are fabricated, which present tunable tissue adhesion strength (14.6–83.9 kPa) and microporous structure (8–18 µm), and lower hemolysis <1.5%. Remarkably, the microporous size mainly controls the hemostasis, and those hydrogels with larger pores of 16–18 µm achieve the fastest hemostasis of ≈14 s and the lowest blood loss of ≈6% than fibrin glue and others. Moreover, both biocompatibility and hemostasis affect wound healing performance, as assessed by hemolysis, cytotoxicity, subcutaneous implantation, and hemostasis and healing assays. Importantly, the glycopolypeptide hydrogel‐treated rat‐skin defect model achieves full wound closure and regenerates thick dermis and epidermis with some hair follicles on day 14. Consequently, this work not only establishes a versatile method for constructing glycopolypeptide hydrogels with tunable adhesion and microporous structure, fast hemostasis, and superior healing functions, but also discloses a useful rationale for designing high‐performance hemostatic and healing hydrogels.

Multifunctional Single‐Component Polypeptide Hydrogels: The Gelation Mechanism, Superior Biocompatibility, High Performance Hemostasis, and Scarless Wound Healing

“…As a single‐component polypeptide model, the dopamine‐grafted poly( l ‐glutamate) (P m DA n , in which m and n denote the degree of polymerization and the degree of DA grafting, respectively) was synthesized to test how it gels in phosphate buffer solution (PBS, 10 m m , pH 7.4). Although the Fe 3+ ‐catechol coordination is generally utilized to crosslink catechol‐containing polymers to form hydrogels, [ 32,39 ] the negatively charged P 300 DA 20 would precipitate in the presence of FeCl 3 . Serendipitously, when P 300 DA 20 was dialyzed or incubated in 0.05 m NaHCO 3 for 24 h, frozen at –18 °C for 24 h, and then thawed at room temperature, it would gel at an ultralow C cgc of 0.1 wt%, as determined by rheometry (Figures S2 and S4, Supporting Information); in contrast, P 300 DA 20 that was treated in PBS would not form a hydrogel when dealt with same procedure.…”

“…In another path, when the lyophilized P 300 DA 20 that was treated by the above protocols was dissolved in PBS at room temperature, it would instantly gel at ≥0.4 wt%, as observed by an inverted tube method (i.e., the hydrogel did not flow within 30 s). [ 32 ] Note that C cgc determined by the inverted tube method is slightly higher than that measured by rheometry, which is due to the gravity effect. [ 1,4,9,15 ]…”

“…[ 29 ] Furthermore, some polypeptide hydrogel‐based sealants have been developed for hemostasis and wound healing as they can promote tissue regeneration and remodeling processes. [ 30–35 ] Very recently, a genetically engineered supercharged polypeptide was complexed with anionic aromatic surfactant to form a bioglue, which could stop bleeding in ≈1 min and accelerate ≈96% wound healing within 8 days. [ 36 ] However, the skin scarring that is hallmarked by lack of secondary appendages (e.g., hair follicles) is still a big hurdle to inhibit a full wound healing process, causing structural, mechanical, functional losses in the healed tissues.…”

“…The polypeptide hydrogels including Gel 1 1 , Gel 2 1 , and Gel 3 1 show better hemostasis with a shorter hemostasis time of ≈60 s and a lower blood loss of ≈10% than commercial cyanoacrylate‐based sealant 4011 (≈110 s, 19.5% blood loss) and Fibrin glue (≈60 s, 40% blood loss). [ 32 ] Especially the polypeptide/graphene oxide (GO) hybrid hydrogel (i.e., Gel 1 1 GO 0.5 ) performs the fastest and the most efficient hemostasis of 12 s and 1.4% blood loss, surpassing most polymeric hydrogels and commercial counterparts (Figure S3, Supporting Information). Remarkably, both Gel 1 1 and Gel 2 1 achieve the best 100% wound healing and regenerate thick dermis with some embedded hair follicles than Gel 1 1 GO 0.5 and Tegaderm on day 14, demonstrating that they can promote highly efficient wound healing to inhibit skin scarring.…”

Highly Adhesive Antibacterial Bioactive Composite Hydrogels With Controllable Flexibility and Swelling as Wound Dressing for Full-Thickness Skin Healing

“…The histocompatibility of hydrogels in vivo was evaluated by subdermal implantation as the reference described ( Teng et al, 2021 ; Zhou et al, 2020 ). Eight-week-old Institute of Cancer Research (ICR) mice (25–30 g) were housed in the Animal Service Centre of Ningbo University.…”