3D-Transglutaminase Fibronectin Hydrogel For The Treatment Of Skin Wounds
Anjali C. Raghuram, BA, Roy P. Yu, BS, Cynthia Sung, BS, Andrea Y. Lo, BS, Sun Young Park, MS, Wan Jiao, MD, PhD, Alex K. Wong, MD.
University of Southern California, Los Angeles, CA, USA.
PURPOSE: Hydrogels have emerged as novel drug delivery vehicles and wound dressing adjuncts to effectively treat major skin wounds. The topical application of fibronectin (FN) in a murine irradiated skin model has demonstrated improved wound healing by greater than 20%. However, there is no reported application of hydrogel-facilitated FN delivery to promote wound healing. In this study, the in vitro and in vivo dynamics of 3D-transglutaminase-hydrogel (3DTgH) FN release were evaluated to characterize optimal parameters for the development of a novel wound dressing.
METHODS: 4.5A and 7.5A stiffness 3DTgH with 1ug FN were constructed and plated in either PBS or collagenase type 2 (Col2) to allow gel digestion. Digested samples were assayed with FN ELISA. Additionally, full-thickness skin wounds were created via punch biopsy in 6-week-old BALB/c mice. Wounds were treated with 6A stiffness 3DTgH incorporating human FN and were assessed at 24 and 48h for 3DTgH adsorption and in vivo enzymatic digestion.
RESULTS: Unlike 3DTgH plated in PBS, 3DTgH plated in Col2 gradually dissolved. 4.5A 3DTgH maximally released FN on day 4 and 7.5A 3DTgH maximally released on FN on day 13 with an overall slower rate of FN release. Mice treated with FN 3DTgH demonstrated gel shrinkage over 48h with tighter adsorption of residual gel to the wound bed at 48h compared to at 24h.
CONCLUSION: 3DTgH is a suitable construct for gradual FN release. Hydrogel-based dressings have high potential for clinical translation and sustained FN delivery for skin wound treatment.
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