Improved Wound Closure Rates and Mechanical Properties Resembling Native Skin in Murine Diabetic Wounds Treated with a Tropoelastin and Collagen Wound Healing Device

Context and background: Chronic non-healing wounds are a major healthcare burden across the globe [1]. Individuals with diabetes are at higher risk and some wounds can take years to heal. Biomimetic scaffolds are being explored as treatment options, to mimic the extracellular matrix of skin and help restore the damaged tissue [2]. Collagen and elastin are two of the multiple matrix elements that contribute to normal wound healing progression [3,4]. This study developed a Wound Healing Device (WHD), a biomimetic scaffold made of collagen and tropoelastin, and studied the healing properties of it in diabetic mice.

Experimental setup: The WHD was created as a circular scaffold, using a 9:1 ratio of human dermal collagen I and recombinant human dermal tropoelastin. The study made use of a diabetic mouse model (strain C57BKS.Cg-m+/+Leprdb/J mice (db/db), with 72 six to eight-week-old mice, 36 of which were male, and 36 female). The mice were wounded and treated with either the WHD or commercially available porcine intestinal sub-mucosa membrane (Oasis Wound Matrix). These were also compared to an untreated control group and wound healing over 28 days was monitored. At 14-day and 28-day timepoints, histology, immunohistochemistry, qPCR and mechanical tests were also performed.

 

Important Results:

Wound closure is greater during the early period for WHD: Compared to Oasis, WHD and control groups showed greater percent wound closure from day 6 to 16. Even though there was no difference between the 3 groups after 20 days, WHD treated wounds achieved closure faster up to day 16. It would be interesting to see if this early period difference confers an advantage to WHD treated wounds in the case of infections.

 

WHD-treated animals showed well-formed remodelled skin: Histological analysis revealed that compared to the Oasis and control groups, the WHD-treated group had a well-formed remodelled skin (including dermis, epidermis, hair follicles). This was similar to unwounded skin in the animals.

 

WHD-treated wounds progress through the inflammatory phase of wound healing: The levels of CD163 (an indirect readout of inflammation) were compared between the 3 groups. WHD-treated wound had lower expression of CD163+ cells compared to Oasis-treated wounds at day 14. This indicates that WHD treatment had less inflammation and had progressed to further stages of wound healing. The Oasis-treated wounds showed a reduction in CD163+ cells at day 28, but these levels were still higher than WHD-treated wounds.

 

Mechanical factors of WHD healed wounds were similar to unwounded skin: Mechanical testing to evaluate Elastic modulus revealed that Oasis-treated wound produced a stiffer remodelled skin tissue compared to WHD and control. The WHD-treated tissue had similar mechanics to unwounded skin.

 

Overall, the WHD resulted in faster wound closure and a remodelled tissue structure that closely mimicked unwounded skin.

 

What I found interesting about this preprint: The WHD did perform better than the commercial product tested (Oasis Wound Matrix). This is promising, since it can help reduce the usage of animal-based products for treatment and replace them with scaffolds that make use of human proteins, making them more human-relevant.

 

Questions for the authors:

1. Has the WHD been evaluated for infected wounds? In such cases, can the WHD incorporate antimicrobials to perform a dual role of clearing the infection and assist in wound healing via the matrix proteins?
2. Is the collagen deposition in the wounds different for the two treatment groups?

 

References/Further Reading:

1. Frykberg, Robert G., and Jaminelli Banks. “Challenges in the treatment of chronic wounds.” Advances in wound care9 (2015): 560-582.
2. Gianino, Elizabeth, Craig Miller, and Jordon Gilmore. “Smart wound dressings for diabetic chronic wounds.” Bioengineering3 (2018): 51.
3. Xue, Meilang, and Christopher J. Jackson. “Extracellular matrix reorganization during wound healing and its impact on abnormal scarring.” Advances in wound care3 (2015): 119-136.
4. Chattopadhyay, Sayani, and Ronald T. Raines. “Collagen‐based biomaterials for wound healing.” Biopolymers8 (2014): 821-833.

Tags: wound healing

doi: https://doi.org/10.1242/prelights.25377

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