Natural Dual‐Crosslinked Self‐Healing Hydrogels for In Situ Wound Healing

Abstract

Poly(l‐glutamic acid) (PLGA), a polypeptide prepared by bacteria fermentation, has broad applications in tissue engineering. A natural host–guest pair of β‐cyclodextrin (β‐CD) and bile acid molecules are attached covalently onto the PLGA backbones separately, and host–guest crosslinked self‐healing hydrogels can be easily formed by mixing these polymer solutions. Inspired by the adhesives of mussel foot proteins, a dopamine methyl acrylamide derivative is introduced into this system to prepare a PLGA‐based dual‐network hydrogel in situ through the combination of host–guest crosslinking and the photo‐crosslinking of the dopamine derivative. The mechanical properties of the hydrogels can be tuned by altering the molar ratios of β‐CD and bile acid as well as the content of dopamine methyl acrylamide derivative. The dynamic inclusion complexation of β‐CD and bile acid allows the hydrogel to self‐heal rapidly under ambient atmosphere and their mechanical properties can recover to original levels within 1 min as evidenced in rheological results. The dual‐network hydrogels exhibit stronger adhesion behavior to pig skin than the host–guest crosslinked hydrogels in vitro. The adhesion of the dual‐network hydrogels to rat whole cortical incision has promoted faster wound healing and tissue regeneration than that in sutured treatments in vivo.

In situ light‐activated materials for skin wound healing and repair: A narrative review

“…41 (20 mW/cm 2 , 10 min). 43 The authors observed similar wound closure to sutures with better cosmesis, with no "railroad tracks" observed in hydrogel-sealed incisions. 43 45 When tested in athymic nu/nu mice with 365 nm in situ crosslinking, heparincontaining hydrogels facilitated faster wound closure versus hyaluronic acid hydrogels alone, demonstrating a therapeutic effect of retained cytokines secreted by the embedded stem cells.…”

“…43 The authors observed similar wound closure to sutures with better cosmesis, with no "railroad tracks" observed in hydrogel-sealed incisions. 43 45 When tested in athymic nu/nu mice with 365 nm in situ crosslinking, heparincontaining hydrogels facilitated faster wound closure versus hyaluronic acid hydrogels alone, demonstrating a therapeutic effect of retained cytokines secreted by the embedded stem cells. 45 Chen et al incorporated FDA-approved desferrioxamine copper chelating agents in GelMA hydrogels (0.5% wt/vol Irgacure 2959) and tested their efficacy in streptozotocin-induced diabetic impaired wounds in Sprague Dawley rats with in situ activation at 6.9 mW/cm 2 UV light (360-480 nm) for 1 min.…”

“… 43 The authors observed similar wound closure to sutures with better cosmesis, with no “railroad tracks” observed in hydrogel‐sealed incisions. 43 Xu et al investigated a composite hydrogel containing methacrylated quaternary ammonium chitosan, polyvinylpyrrolidone, and dopamine (DOPA) photoinitiated by 0.7% wt/vol Irgacure 2959 and tested its efficacy with multifunctional DOPA‐mediated NIR‐induced photothermal microbial clearance in an S. aureus ‐infected full‐thickness wound model in Balb/c mice with in situ photocuring with irradiation at 365 nm (260 mW/cm 2 ) for 15 s. 44 Interestingly, the hydrogel with or without NIR irradiation resulted in enhanced wound closure with only slight enhancement by photothermal activation, demonstrating the intrinsic therapeutic efficacy of the hydrogel alone. 44 Skardal et al successfully produced hydrogels without methacrylate moieties by using thiolated hyaluronic acid, heparin, and gelatin constituents crosslinked with PEGDA initiated by Irgacure 2959 (2% wt/vol) to deliver amniotic fluid‐derived stem cells for wound repair via in situ bioprinting.…”

“…Wang et al developed a self‐healing hydrogel composed of methacrylated PLGA and cyclodextrin‐conjugated PLGA photoinitiated by Irgacure 2959 (5% of formulation weight). The crosslinked hydrogels were tested in an incisional wound healing model in Sprague Dawley rats with in situ activation by 365‐nm light (20 mW/cm 2 , 10 min) 43 . The authors observed similar wound closure to sutures with better cosmesis, with no “railroad tracks” observed in hydrogel‐sealed incisions 43 .…”

“…The crosslinked hydrogels were tested in an incisional wound healing model in Sprague Dawley rats with in situ activation by 365‐nm light (20 mW/cm 2 , 10 min) 43 . The authors observed similar wound closure to sutures with better cosmesis, with no “railroad tracks” observed in hydrogel‐sealed incisions 43 . Xu et al investigated a composite hydrogel containing methacrylated quaternary ammonium chitosan, polyvinylpyrrolidone, and dopamine (DOPA) photoinitiated by 0.7% wt/vol Irgacure 2959 and tested its efficacy with multifunctional DOPA‐mediated NIR‐induced photothermal microbial clearance in an S. aureus ‐infected full‐thickness wound model in Balb/c mice with in situ photocuring with irradiation at 365 nm (260 mW/cm 2 ) for 15 s 44 .…”