Wound Healing Versus Regeneration: Role of the Tissue Environment in Regenerative Medicine
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Versus Regeneration: Role of the Tissue Environment in Regenerative Medicine
Anthony Atala, Darrell J. Irvine, Marsha Moses, and Sunil Shaunak Abstract One of the major challenges in the field of regenerative medicine is how to optimize tissue regeneration in the body by therapeutically manipulating its natural ability to form scar at the time of injury or disease. It is often the balance between tissue regeneration, a process that is activated at the onset of disease, and scar formation, which develops as a result of the disease process that determines the ability of the tissue or organ to be functional. Using biomaterials as scaffolds often can provide a “bridge” for normal tissue edges to regenerate over small distances, usually up to 1 cm. Larger tissue defect gaps typically require both scaffolds and cells for normal tissue regeneration to occur without scar formation. Various strategies can help to modulate the scar response and can potentially enhance tissue regeneration. Understanding the mechanistic basis of such multivariate interactions as the scar microenvironment, the immune system, extracellular matrix, and inflammatory cytokines may enable the design of tissue engineering and wound healing strategies that directly modulate the healing response in a manner favorable to regeneration.
Introduction A tissue’s natural response to injury or disease is associated with fibroblast deposition and scar formation. Scar tissue is often formed at the expense of normal tissue regeneration. The result of all significant injury and organ failure, regardless of the origin, is the presence of scar tissue. Often the balance between tissue regeneration, a process that is activated at the onset of injury or disease, and scar formation determines the ability of the tissue or organ to be
functional. Using biomaterials as scaffolds often can provide a “bridge” for normal tissue edges to regenerate. Regenerative medicine uses various strategies for the management of disease or injury, including mechanisms that can enhance in situ tissue regeneration, the use of biomaterials, the use of cells for therapy, or the combination of biomaterials and cells for therapy or tissue engineering. The immune system plays a key role during wound healing. It functions to
MRS BULLETIN • VOLUME 35 • AUGUST 2010 • www.mrs.org/bulletin
sterilize the site of injury and remove dead or dying cells. Leukocytes also produce a host of inflammatory and anti-inflammatory cues that regulate the function of diverse cell types in vivo and can help or hinder wound healing, depending on the state of the local tissue microenvironment. In the context of regenerative medicine, the interaction of immune cells with both host and donor cells, the local matrix, and biomaterials must all be considered for successful tissue regeneration. A critical prerequisite for successful tissue regeneration is appropriate extracellular matrix (ECM) remodeling. This process requires the tightly regulated synthesis and degradation of ECM components. Key players in this regulat
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