Acute cutaneous wounds treated with human decellularised dermis show enhanced angiogenesis during healing.

Abstract

BACKGROUND:

The influence of skin substitutes upon angiogenesis during wound healing is unclear.

OBJECTIVES:

To compare the angiogenic response in acute cutaneous human wounds treated with autogenic, allogenic and xenogenic skin substitutes to those left to heal by secondary intention.

METHODS:

On day 0, four 5mm full-thickness punch biopsies were harvested from fifty healthy volunteers (sites 1-4). In all cases, site 1 healed by secondary intention (control), site 2 was treated with collagen-GAG scaffold (CG), cadaveric decellularised dermis (DCD) was applied to site 3, whilst excised tissue was re-inserted into site 4 (autograft). Depending on study group allocation, healing tissue from sites 1-4 was excised on day 7, 14, 21 or 28. All specimens were bisected, with half used in histological and immunohistochemical evaluation whilst extracted RNA from the remainder enabled whole genome microarrays and qRT-PCR of highlighted angiogenesis-related genes. All wounds were serially imaged over 6 weeks using laser-doppler imaging and spectrophotometric intracutaneous analysis.

RESULTS:

Inherent structural differences between skin substitutes influenced the distribution and organisation of capillary networks within regenerating dermis. Haemoglobin flux (p = 0.0035), oxyhaemoglobin concentration (p = 0.0005), and vessel number derived from CD31-based immunohistochemistry (p = 0.046) were significantly greater in DCD wounds at later time points. This correlated with time-matched increases in mRNA expression of membrane-type 6 matrix metalloproteinase (MT6-MMP) (p = 0.021) and prokineticin 2 (PROK2) (p = 0.004).

CONCLUSION:

Corroborating evidence from invasive and non-invasive modalities demonstrated that treatment with DCD resulted in increased angiogenesis after wounding. Significantly elevated mRNA expression of pro-angiogenic PROK2 and extracellular matrix protease MT6-MMP seen only in the DCD group may contribute to observed responses.

• Authors: Nicholas S Greaves, Syed A Lqbal, Julie Morris, Brian Benatar, Teresa Alonso-Rasgado, Mohamed Baguneid, Ardeshir Bayat
• Journal: PloS one (PLoS One) Vol. 10 Issue 1 Pg. e0113209 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 25602294 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• Basic Helix-Loop-Helix Transcription Factors
• Gastrointestinal Hormones
• HIF3A protein, human
• Neuropeptides
• PROK2 protein, human
• Repressor Proteins
• endothelial PAS domain-containing protein 1

Topics

• Apoptosis Regulatory Proteins
• Basic Helix-Loop-Helix Transcription Factors (genetics, metabolism)
• Dermis (blood supply, metabolism)
• Gastrointestinal Hormones (genetics, metabolism)
• Gene Expression
• Gene Expression Profiling
• Humans
• Immunohistochemistry
• Neovascularization, Physiologic (genetics)
• Neuropeptides (genetics, metabolism)
• Repressor Proteins
• Skin, Artificial
• Wound Healing (physiology)
• Wounds and Injuries (genetics, pathology, surgery)