20.109(S10):Notebook/T/R Orange Research Proposal

Project Overview
Tissue engineering is an emerging field that aims to regenerate tissues and organs. Skin regeneration is a naturally observed phenomenon. Different biomaterials have been developed to mimic skin; however, there is still not a skin substitute that replicates all of skin's properties including biological function and aesthetics. Also to be noted, in wound healing, the skin regenerated to cover a wound is often scar tissue that has a different texture and some loss of function. With tissue engineering it is a goal to be able to get one's own skin to regenerate to produce a biological barrier that is both functional and aesthetically pleasing.


 * We hope to create a better solution for skin regeneration

Background information
There is great need for a cost-effective tissue engineered construct (TEC) which can treat both acute and chronic wounds. There are two possible approaches: a skin replacement can be grown in vitro and then transplanted in vivo, or a resorbable matrix can be inserted which recruits native tissue cells and induces them to heal the wound.

Article Summaries
L. Macri, R.A.F. Clark. Tissue Engineering for Cutaneous Wounds: Selecting the Proper Time and Space for Growth Factors, Cells and the Extracellular Matrix. Skin Pharmacol Physiol 2009;22:83–93 DOI: 10.1159/000178867. Published online: February 4, 2009. http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ArtikelNr=000178867&Ausgabe=243468&ProduktNr=224194&filename=000178867.pdf

This article was a review of current methods used in engineered wound healing. It provides a helpful overview of the components necessary to consider when designing new wound treatments (cells, ECM, and bioactive molecules), notes current solutions and their downfalls, and presents goals to strive for in future projects.

Current approaches for dermal-like biological dressings:
 * Integra-made of bovine collagen and shark cartilage (nonideal: animal products, not a good surface for epidermal sheet engraftment)
 * Transcyte-made of ECM deposited on a nylon scaffold by neonatal human foreskin fibroblasts (quality control issues)
 * Dermagraft-ECM deposited on a lactide-glycolide polymer (quality control issues)
 * Organotypic skin (Apligraf and Orcel)-developed through tissue engineering (expensive, not long-lived, not durable, although 2nd generation is better)

Anthony D Metcalfe and Mark W.J Ferguson. Tissue engineering of replacement skin: the crossroads of biomaterials, wound healing, embryonic development, stem cells and regeneration. J R Soc Interface. 2007 June 22; 4(14): 413–437. Published online 2006 December 5. doi: 10.1098/rsif.2006.0179. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2373411/?tool=pmcentrez

There are many factors to consider in skin tissue engineering. Skin is protective and serves as a line of defense against bacteria, evaporation, UV light, etc. The multifunctional properties of skin are what make it so complex to reproduce.

When skin is damaged or diseased, it is often very difficult to fix. Even though our bodies have the ability to regenerate skin, the new skin is often scar tissue that has loss some function and aesthetics. Smart skin replacement therapies often include a scaffold and controlled release of cytokines to direct cell migration and proliferation in a manner that would produce the many different layers of skin. Scaffolds help greatly to make the skin "thicker" like normal skin. This article also summarizes the different skin substitutes currently being developed, and their problems like lack of pores and decrease elasticity.