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November 5, 2019

Bioinspired Adhesive Dressing Actively Heals Wounds in Animals

JAMA. 2019;322(17):1642-1643. doi:10.1001/jama.2019.16734

To create a novel wound adhesive that accelerates wound healing, scientists recently drew inspiration from embryonic processes that pull wound edges together like a purse-string to regenerate fetal skin without inflammation or scarring.

In research described in Science Advances, investigators designed what they called active adhesive dressings (AADs) that exert contractile forces sufficient to promote active wound closure. Gauzes, cotton wools, and dressings conventionally used to treat skin injuries rely on slow and passive healing processes, which can be insufficient when caring for certain traumatic injuries, chronic wounds, and aging populations with diminished wound-healing ability.

The AADs consist of thermoresponsive adhesive hydrogels that combine high elasticity, toughness, tissue adhesion, and antimicrobial properties. “This study is built on the tough adhesive hydrogels we developed and reported on in 2017, as well as the hydrogel-based wound dressings that are widely used in clinics. It is also inspired by clinical use of negative pressure wound therapies and the recent demonstration of mechanically driven muscle regeneration,” said co–first author Jianyu Li, PhD, a former postdoctoral fellow at the Wyss Institute for Biologically Inspired Engineering at Harvard University who is now an assistant professor at McGill University in Montreal.

The AADs contain a polymer known as poly(N-isopropyl acrylamide), which both repels water and shrinks at around 90°F. Therefore, the AADs generate contractile forces in response to body heat when placed on a wound with no requirement for additional reagents or external stimuli. They are so strongly adhesive that they efficiently transfer these contractile forces to the underlying wound edges. This was achieved by bonding the adhesive hydrogel to the underlying tissue via chitosan- and carbodiimide-mediated reactions. The AADs also contain silver nanoparticles (which are widely used in wound care products) to give the hydrogel antimicrobial functions.

Wyss Institute at Harvard University

In pigs, the dressings adhered to underlying tissue better than Band-Aid dressings. When tested on patches of explanted mouse skin, the AADs reduced the size of the wound area by approximately 45% compared with minimal changes after applying a nonthermoresponsive tough adhesive or no treatment.

In living rodents with wounds, AAD treatment applied underneath conventional dressings (Tegaderm, a transparent medical dressing, and Band-Aid) significantly accelerated wound closure more than 2-fold by day 3 compared with conventional dressings alone or a nonthermoresponsive tough adhesive. All conditions exhibited similar levels of inflammation and no severe immune responses, indicative of good biocompatibility.

“Our findings surprised us in terms of the accelerating effect of our dressings on wound closure: substantial wound closure was observed as early as day 3, compared with a small change under control conditions with a clinically used dressing,” said Li.

Experiments also revealed that the rate of wound closure using AADs was comparable with that of photo-crosslinked chitosan hydrogels and microporous gel scaffolds, 2 other innovative wound treatments reported in the literature.

Adding different amounts of acrylamide monomers during the manufacturing process allowed the researchers to fine-tune the contractile behavior of the hydrogels, enabling them to program the level of strain imposed on wound edges. This property could be useful when applying AADs to wounds at dynamic locations such as joints.

Additional studies are needed to provide more detailed information on the range of effects of AADs at the cellular level. “Scientifically, it is important to elucidate how the mechanical contraction affects the biological process of wound healing,” said Li. The scientists’ ongoing and future studies will evaluate the impact of AADs on the expression of genes involved in wound repair and collagen organization as skin heals. They say that it will also be important to examine how AADs affect the activity of relevant cells such as fibroblasts, and how AADs function at different body temperatures.

Although the study provides a novel mechanistic approach to wound dressings, the acute wound mouse model it used does not recapitulate the heterogeneity and complexity of chronic wounds in humans such as diabetic ulcers, venous ulcers, and pressure sores, noted Ayman Grada, MD, MS, who studies cutaneous wound healing at Boston University’s School of Medicine. “It is too early to predict the potential clinical impact on chronic wounds in humans,” he said. “Moreover, not all wounds require adhesive dressings. Adherent occlusive dressings are generally not recommended for patients with fragile or sensitive skin, heavily draining wounds, or clinically infected wounds.”

A computer simulation performed using the mechanical properties of human skin predicted that the AADs could induce human skin contraction comparable with that of rodent skin. However, “from a translational perspective, there is a need to test our technology with large animal models and human clinical trials before benefiting patients,” said Li. If such studies are successful, AADs may find applications beyond external wound repair, for example, in internal wound healing, drug delivery, and biomedical devices.