The Role of the Extracellular Matrix (ECM) in Wound Healing: A Review.

The extracellular matrix (ECM) is a 3-dimensional structure and an essential component in all human tissues. It is comprised of varying proteins, including collagens, elastin, and smaller quantities of structural proteins. Studies have demonstrated the ECM aids in cellular adherence, tissue anchoring, cellular signaling, and recruitment of cells. During times of integumentary injury or damage, either acute or chronic, the ECM is damaged. Through a series of overlapping events called the wound healing phases-hemostasis, inflammation, proliferation, and remodeling-the ECM is synthesized and ideally returned to its native state. This article synthesizes current and historical literature to demonstrate the involvement of the ECM in the varying phases of the wound healing cascade.

An acellular tissue engineered biomimetic wound healing device created using collagen and tropoelastin accelerates wound healing.

AIM: Tissue engineering has historically involved research combining scaffolds, cells, and active biomolecules to treat multiple pathologies. The current research seeks to determine if the wound healing cascade can be modulated using acellular scaffolds, engineered to create an acellular electrospun dermal biomimetic. METHODS: The dermal biomimetic has a similar architecture to the dermis, porosity and fiber diameter, as well as physiologically relevant ratios of the primary structural dermal proteins, collagen and tropoelastin. This biomimetic wound healing device (BMWHD) was implanted into a full thickness dermal wound murine model for six days. RESULTS: WHD-treated wounds had 30% greater re-epithelialization with a thicker epidermis, new elastin fibers in the wound bed, and healed architecture that matched unwounded extracellular matrix. CONCLUSIONS: Using these WHDs that closely match the native architecture and protein concentrations, accelerated the wound through the wound healing cascade and supports the hypothesis that structure alone can influence function when engineering acellular dermal biomimetic devices.

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

Chronic wounds in patients suffering from type II diabetes mellitus (DMII) where wounds remain open with a complicated pathophysiology, healing, and recovery process is a public health concern. Normal wound healing plays a critical role in wound closure, restoration of mechanical properties, and the biochemical characteristics of the remodeled tissue. Biological scaffolds provide a tissue substitute to help facilitate wound healing by mimicking the extracellular matrix (ECM) of the dermis. In the current study an electrospun biomimetic scaffold, wound healing device (WHD), containing tropoelastin (TE) and collagen was synthesized to mimic the biochemical and mechanical characteristics of healthy human skin. The WHD was compared to a commercially available porcine small intestinal submucosa (SIS) matrix that has been used in both partial and full-thickness wounds, Oasis® Wound Matrix. Using a diabetic murine model C57BKS.Cg-m+/+Leprdb/J mice (db/db) wound closure rates, histochemistry (CD31 and CD163), qPCR (GAPDH, TNF-α, NOS2, ARG1 and IL10), and mechanical testing of treated wound sites were evaluated. The WHD in a splinted, full thickness, diabetic murine wound healing model demonstrated skin organ regeneration, an enhanced rate of wound closure, decreased tissue inflammation, and a stronger and more durable remodeled tissue that more closely mimics native unwounded skin compared to the control device.

Pilot study: Autologous platelet-rich plasma used in a topical cream for facial rejuvenation.

BACKGROUND: Platelet rich plasma (PRP) is traditionally used as an injectable material for enhanced healing, hair growth, and facial rejuvenation. AIMS: This research examined the novel use of topical autologously sourced PRP added to a preservative cosmetic base and applied twice daily to the face following electroporation for 8 weeks. METHODS: 20 healthy female and male subjects 30-60 years of age were enrolled in this single-site, investigator blinded, vehicle controlled split-face study to evaluate the effect of a PRP-containing serum versus the serum alone on facial photoaging. RESULTS: 90 day stability for the PRP in a preservative serum was achieved with refrigeration at 4 degrees Celsius. Facial skin biopsy histologic findings included improved rete peg architecture. Immunohistochemical analysis showed upregulation for collagen type I with qPCR data demonstrating concomitant upregulation of mRNA for collagen after 8 weeks of topical PRP use. CONCLUSION: These pilot study findings may indicate value for topical PRP in facial rejuvenation.

A Bench-Top In Vitro Wound Assay to Demonstrate the Effects of Platelet-Rich Plasma and Depleted Uranium on Dermal Fibroblast Migration.

Cellular migration assays are useful tools to investigate physiologic events on the bench top. Furthermore, this migration assay can be utilized to investigate wound healing therapeutics (those that encourage or accelerate wound closure) as well as deleterious agents (ones that mitigate or slow wound closure). The current study used an in vitro scratch assay to measure the effects of platelet-rich plasma (PRP) and depleted uranium (DU) in the form of uranyl acetate on cellular migration of human neonatal dermal fibroblasts in an in vitro simulation of wound healing. Data analyses included percent wound closure measured as the distance between cell margins, and rates of wound closure versus untreated controls. The highest doses of PRP (0.063, 0.125%) resulted in 50-65% wound closure after 4-8 hours relative to 38-44% in controls and the low-dose treatment group (0.031%). The high-dose treatments of PRP (0.125, 0.063%) reached 100% wound closure at 12 hours postwound versus 16 hours for controls and the low-dose treatment group (0.031%). Conversely, the higher doses of DU treatments (50 and 100 µM) resulted in <80% closure versus 100% closure in controls after 16 hours, with full closure observed at 20 hours. The highest dose of DU (1,000 µM) resulted in <20% closure versus 100% closure in controls after 16 hours. The use of the described scratch assay serves as a translatable bench-top model that has the potential to predict in vivo outcomes, and in many early studies can help to demonstrate proof-of-concept before moving into complex biological systems.

Validating whole slide digital morphometric analysis as a microscopy tool.

Whole slide imaging (WSI) can be used to quantify multiple responses within tissue sections during histological analysis. Feature Analysis on Consecutive Tissue Sections (FACTS®) allows the investigator to perform digital morphometric analysis (DMA) within specified regions of interest (ROI) across multiple serial sections at faster rates when compared with manual morphometry methods. Using FACTS® in conjunction with WSI is a powerful analysis tool, which allows DMA to target specific ROI across multiple tissue sections stained for different biomarkers. DMA may serve as an appropriate alternative to classic, manual, histologic morphometric measures, which have historically relied on the selection of high-powered fields of views and manual scoring (e.g., a gold standard). In the current study, existing preserved samples were used to determine if DMA would provide similar results to manual counting methods. Rodent hearts (n=14, left ventricles) were stained with Masson's trichrome, and reacted for cluster of differentiation 68 (CD-68). This study found no statistical significant difference between a classic, manual method and the use of digital algorithms to perform the similar counts (p=0.38). DMA offers researchers the ability to accurately evaluate morphological characteristics in a reproducible fashion without investigator bias and with higher throughput.