(WHS-K4.01) TYPE III COLLAGEN BIOMATERIALS IMPROVE CUTANEOUS WOUND HEALING IN DIABETIC MICE
Thursday, May 16, 2024
9:15 AM – 10:15 AM East Coast USA Time
Background: Dysregulated collagen production and proteolytic degradation of collagen in diabetic wounds is well known to contribute to impaired healing in diabetic patients. Altered dynamic reciprocity between cells in the healing microenvironment in turn leads to altered epithelial, stromal, and immune cell responses after injury. Based on our previous work showing a vulnerary and pro-regenerative role for type III collagen (Col3) in acute wound repair, we hypothesized that delivery of Col3 to diabetic wounds could improve efficiency and quality of repair in a diabetic mouse model. Furthermore, we have developed a proteolytic-resistant Col3 (aza-Col3) which we hypothesize will further improve efficacy of Col3 biomaterials in diabetic wound healing.
Methods: Two 8 mm full-thickness excisional wounds were made paramedian on the dorsum of LepRdb/db (db/db) mice at 14-16 weeks of age. Shear-thinning, self-healing hydrogels were utilized to deliver rhCol3 (200 μg) or vehicle to the wound bed at the time of wounding. Wounds were collected and gross wound closure was assessed at 7-, 10-, and 14-days post-wounding (DPW). Histomorphometry was determined for total re-epithelialized distance (RE), epidermal gap (EG), and granulation tissue (GT) area on H&E sections. Immune responses were characterized by immunohistochemical staining for MPO and F4/80 (neutrophils and macrophages, respectively). rhCol3 degradation with or without aza-glycine peptides (aza-Col3) was assessed with circular dichroism (CD) spectroscopy in the presence of collagenases.
Results: We observed that Col3 biomaterial-containing wounds had improved wound healing as evidenced by increased RE at 7, 10, and 14 DPW compared to control biomaterial wounds (p < 0.01 for each timepoint); decreased EG at 7 and 14 DPW (p < 0.05); and increased GT formation at 10 DPW (p < 0.05). At 10 DPW, Col3 biomaterial wounds had decreased neutrophil (MPO+ cells) and macrophage (F4/80+ cells) infiltration compared to controls (p < 0.05 each). CD spectra revealed increased resistance to degradation in aza-Col3 samples dose-dependently with increasing aza-glycine concentration compared to rhCol3 alone.
Conclusions: Our results demonstrate that Col3 improves wound healing outcomes in a diabetic mouse model through its effects on re-epithelization, GT formation, and immune response. While the incorporation of Col3 alone improved wound healing outcomes, preliminary data also indicate that incorporation of aza-peptides with Col3 prevents degradation in the presence of collagenases and suggest that aza-Col3 biomaterials may further improve healing outcomes in diabetic wounds.