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Mitigation Of Hypertrophic Scar Contraction And Stiffening Via An Elastomeric Biodegradable Scaffold
Mohamed M. Ibrahim, MD1, Elizabeth R. Lorden, BS2, Kyle J. Miller, BA1, Latif Bashirov, MD1, Ellen Hammett, BS2, Manuel Medina, MD1, Youngmee Jung, BS3, Ali Rastegarpou, MD1, Angelica M. Selim, MD4, Kam W. Leong, PhD5, Howard Levinson, MD1.
1The Division of Plastic and Reconstructive Surgery, Department of Surgery, Duke University School of Medicine, Durham, NC, USA, Durham, NC, USA, 2Department of Biomedical Engineering, Duke University, Durham, NC, USA, Durham, NC, USA, 3Korea Institute of Science and Technology Biomaterials Research Center, Korea, Korea, Republic of, 4Duke University Medical Center, Department of Pathology, Durham, NC, USA, 5Columbia University, Department of Biomedical Engineering, New York, NY, USA.
Hypertrophic scar (HSc) occurs in 40-70% of patients treated for third degree burn injuries. Current burn therapies rely upon using bioengineered skin equivalents (BSEs), which assist in wound healing but do not prevent HSc contraction. Contractures are painful and disfiguring. We propose to develop BSEs that can persist throughout the remodeling phase of repair. In this study we investigate the impact of degradable and elastomeric poly(l-lactide-co-ε-caprolactone) (PLCL) on HSc contraction.
Electrospinning was used to generate randomly aligned, PLCL scaffolds with an average fiber diameter of 6µm. After surface treatment with bovine type I collagen, collagen coated PLCL (ccPLCL) scaffolds were characterized for tensile and fatigue properties, and compared to Integra, human skin, and human scar tissue. ccPLCL scaffolds were surgically inserted beneath skin grafts in a validated immune-competent murine HSc contraction model for four, eight, and sixteen weeks, with comparison to skin graft alone or Integra. Tensile testing was carried out on uninjured mouse skin as compared to scar tissue harvested from mice treated with ccPLCL, Integra, and skin graft alone. Degradation analysis of explanted ccPLCL scaffolds was evaluated by GPC and NMR.
The elastic moduli of ccPLCL and Integra were significantly less than human skin and scar. The ultimate tensile stress for ccPLCL scaffolds, human skin, and human scar were significantly greater than that of Integra. In contrast, the elongation at break for ccPLCL scaffolds was significantly higher than the values obtained for, human skin, and human scar. Storage modulus and loss modulus of ccPLCL scaffold showed negligible deterioration over 24h, or 15,000 cycles.
Murine wounds treated with skin grafts alone contracted to ~47% at d30, while wounds treated with Integra contracted to ~28%. In contrast, wounds treated with ccPLCL scaffolds showed significantly decreased contraction, down to ~95% at d30. D30 ccPLCL explants exhibited an elastic modulus, significantly lower than tissue alone in both mouse skin and scar samples, although not significantly different from that prior to implantation. The molecular weight of scaffolds decreased by 49% from Mn=151 kDa to ~73.2kDa over the implanted period. NMR analysis shows that the lactide (LA) moiety was noticeably more rapidly decreased than the caprolactone (CL) units. The mole fraction of LA decreased from 50% to 44% in 30 days, while that of CL increased from 50% to 56%.
PLCL scaffolds displayed appropriate elastomeric and tensile characteristics for implantation beneath a human skin graft. HSc contraction was significantly greater in animals treated with Integra, as compared to those treated with ccPLCL scaffolds. Wounds treated with ccPLCL were significantly less stiff than control wounds at d30 in vivo. Degradation of PLCL at d30 in vivo was evidenced by decreasing Mn, increasing PDI, and altered CL:LA ratio. These data suggest that scaffolds which persist throughout the remodeling phase of repair may represent a clinically translatable method to prevent HSc contraction.
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