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Annals of Biomedical Engineering, Vol. 42, No. 7, July 2014 ( 2014) pp. 15171527 DOI: 10.1007/s10439-013-0963-7
Decellularized Allogeneic and Xenogeneic Tissue as a Bioscaffold for Regenerative Medicine: Factors that Inuence the Host Response
STEPHEN F. BADYLAK1,2,3
1McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219-3130, USA; 2Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA; and 3Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA
(Received 16 July 2013; accepted 10 December 2013; published online 9 January 2014)
Associate Editor Song Li oversaw the review of this article.
AbstractBiologic scaffold materials composed of mammalian extracellular matrix (ECM) are prepared by decellularization of source tissues harvested from either humans (allogeneic) or a variety of other (xenogeneic) species. These matrix scaffold materials are commonly regulated and used as surgical mesh materials for applications such as ventral hernia repair, musculotendinous tissue reconstruction, dura mater replacement, reconstructive breast surgery, pelvic oor reconstruction, and the treatment of cutaneous ulcers, among others. The clinical results for these applications vary widely for reasons which include characteristics of the source tissue, methods and efcacy of tissue decellularization, and methods of processing/manufacturing. However, the primary determinant of success or failure in the clinical setting is the response of the host to these implanted biologic scaffold materials. It is logical to question why any non-self biologic material, particularly a xenogeneic material, would not elicit an early and aggressive adverse immune response. The present manuscript briey describes the known mechanisms by which these biologic scaffold materials can facilitate a constructive remodeling response, the known causative factors of an adverse response, and provides a general discussion of the role of the macrophage in determining outcome.
ABBREVIATIONS
DAMP Damage associated molecular pattern ECM Extracellular matrixGAG GlycosaminoglycanHMGB1 High mobility group box 1SIS Small intestinal submucosa
TE/RM Tissue Engineering and Regenerative
MedicineTLR Toll-like receptorTNFa Tumor necrosis factor alpha
INTRODUCTION
Biologic scaold materials composed of allogeneic or xenogeneic extracellular matrix (ECM) are produced by methods that include decellularization and subsequent processing of source tissues such as dermis, small intestinal submucosa, and urinary bladder, among others.7,9,25,44 Historically, these materials have been uniformly considered by regulatory bodies (e.g., Food and Drug Administration) as medical devices and specically, as surgical mesh materials. However, a recent commercialization attempt...