Wound healing hydrogel activates regenerative immune response

Researchers at Duke University (NC, USA) and the University of California Los Angeles (UCLA; CA, USA) have developed a novel biomaterial that aids the repair of damaged skin through inducing an adaptive and regenerative immune response – whilst reducing scar formation.

Their study, recently published in Nature Materials, builds upon previous research where the team developed microporous annealed particle (MAP) hydrogels. These microparticle-based biomaterials provide a structure to support tissue growth by integrating into the wound, rather than sitting on top like a typical hydrogel.

A modified version of this hydrogel has now been shown to activate a regenerative immune response – helping to repair skin injuries such as burns or cuts whilst avoiding significant scars.

The original MAP gel provided a porous structure to support tissue growth that would slowly dissolve, leaving behind healed skin. However, the team noticed that the resulting skin lacked complex structures such as hair follicles and sebaceous glands.

“Previously we’d seen that as the wound started to heal, the MAP gel started to lose porosity, which limited how the tissue could grow through the structure,” explained lead author of the study, Don Griffin (UCLA). “We hypothesized that slowing down the degradation rate of the MAP scaffold would prevent the pores from closing and provide additional support to the tissue as it grows, which would improve the tissue’s quality.”

To tackle this, the team examined the chemical linker that holds the structure together within the gel. Initially, the linker was formed of an amino acid sequence arranged in an orientation known as L chirality. In an attempt to slow down degradation of this linker (and therefore the hydrogel), the team switched the chirality.

Our body has evolved to recognize and degrade this amino acid structure, so we theorized that if we flipped the structure to its mirror image, which is D chirality, the body would have a harder time degrading the scaffold,” explained study co-author, Tatiana Segura (Duke University). “But when we put the hydrogel into a mouse wound, the updated gel ended up doing the exact opposite.”

Surprisingly, the team saw accelerated degradation of the gel. What’s more – the modified therapy healed the wound whilst producing stronger and more complex skin structures with no scarring. After further investigation the team discovered that this was because the body had a different immune response to the new gel.

“There are two types of immune responses that can occur after injury – a destructive response and a more mild regenerative response,” commented study co-author, Philip Scumpia (UCLA). “When most biomaterials are placed in the body, they are walled off by the immune system and eventually degraded or destroyed. But in this study, the immune response to the gel induced a regenerative response in the healed tissue.”

The L chirality within the original gel was recognized by the body, leading to a destructive innate immune response. However, the foreign D chirality of the updated gel triggered the active immune system – creating antibodies and activated cells including macrophages that targeted and removed the gel more quickly after the wound closed.

“This study shows us that activating the immune system can be used to tilt the balance of wound healing from tissue destruction and scar formation to tissue repair and skin regeneration,” concluded Segura. “I am excited about the possibility of designing materials that can directly interact with the immune system to support tissue regeneration.”

Link: https://www.regmednet.com/wound-healing-hydrogel-activates-regenerative-immune-response/