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Keywords:

  • extracellular matrix;
  • tissue engineering;
  • regenerative medicine;
  • developmental biology

Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. COMPOSITION OF EXTRACELLULAR MATRIX
  5. EXTRACELLULAR MATRIX IN DEVELOPMENTAL BIOLOGY
  6. EXTRACELLULAR MATRIX AS A SCAFFOLD FOR REGENERATIVE MEDICINE APPLICATIONS
  7. ECM BIOLOGIC SCAFFOLDS FOR REPAIR ESOPHAGEAL RECONSTRUCTION
  8. ECM FOR ORTHOPEDIC APPLICATIONS
  9. ECM BIOLOGIC SCAFFOLDS FOR URINARY TRACT RECONSTRUCTION
  10. ALTERNATIVE APPLICATIONS OF ECM BIOLOGIC SCAFFOLDS
  11. SUMMARY
  12. LITERATURE CITED

The principles and ultimate goals of regenerative medicine and developmental biology involve a complex sequence of events, culminating in the formation of structurally and functionally normal tissues and organs. The molecular composition of the extracellular matrix (ECM) plays a critical role in cellular migration and differentiation events. Mammalian ECM, derived from various tissues and organs, has been used as a biologic scaffold for therapeutic regenerative applications. Hundreds of thousands of human patients have benefited from the use of biologic scaffolds composed of naturally occurring ECM. The mechanisms by which ECM induces constructive remodeling instead of scar tissue formation are only beginning to be understood. This article reviews composition of mammalian ECM, its poorly understood role in developmental biology, and the clinical applications that have resulted from the use of this naturally occurring scaffold. Anat Rec (Part B: New Anat) 287B:36–41, 2005. © 2005 Wiley-Liss, Inc.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. COMPOSITION OF EXTRACELLULAR MATRIX
  5. EXTRACELLULAR MATRIX IN DEVELOPMENTAL BIOLOGY
  6. EXTRACELLULAR MATRIX AS A SCAFFOLD FOR REGENERATIVE MEDICINE APPLICATIONS
  7. ECM BIOLOGIC SCAFFOLDS FOR REPAIR ESOPHAGEAL RECONSTRUCTION
  8. ECM FOR ORTHOPEDIC APPLICATIONS
  9. ECM BIOLOGIC SCAFFOLDS FOR URINARY TRACT RECONSTRUCTION
  10. ALTERNATIVE APPLICATIONS OF ECM BIOLOGIC SCAFFOLDS
  11. SUMMARY
  12. LITERATURE CITED

The term “tissue engineering” was coined in 1988 and defined as “the application of the principles and methods of engineering and life sciences toward the fundamental understanding of structure-function relationships in normal and pathological mammalian tissue and the development of biological substitutes to restore, maintain, or improve tissue function.” The term is now frequently used in conjunction with the more encompassing descriptor of “regenerative medicine.” Significant progress has been made in the field with one notable exception. There has been a relative lack of emphasis placed on the understanding of the principles of normal developmental biology and the application of these principles to the ultimate objective of regenerative medicine: the regeneration of structurally and functionally normal body parts.

The approaches taken to recreate tissues and organs have typically involved a combination of cells, scaffolds, and bioactive molecules. All three of these components are obviously necessary in the final construct; however, the complex issues of appropriate three-dimensional spatial organization of cells, innervation, lymphatic and vascular network formation, and immunologic acceptance of nonself components, among others, must be addressed if successful clinical application of these efforts is to be realized. These challenges are nontrivial. It is certain that many different strategies will be attempted before we can recapitulate even a small fraction of the success and efficiency that has resulted from hundreds of millions of years of research and development by Mother Nature.

The present article is confined to a regenerative medicine approach for tissue reconstruction that utilizes the native mammalian extracellular matrix (ECM) as a template or scaffold for the constructive remodeling of tissues and organs (Fig. 1). The composition of the ECM, its function in mammalian embryonic and fetal development and wound repair, and its use as a biologic scaffold in preclinical and clinical studies will be briefly reviewed.

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Figure 1. A tissue-engineered tracheal device measuring approximately 8 cm in length and containing eight separate ring structures, composed of ECM derived from the porcine urinary bladder. This tracheal substitute consists of 6 layers of urinary bladder matrix-ECM (UBM-ECM) laminated around ring structures that themselves are composed of 25 layers of UBM-ECM. [Color figure can be viewed in the online issue, which is available at www.interscience.wiley.com].

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COMPOSITION OF EXTRACELLULAR MATRIX

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. COMPOSITION OF EXTRACELLULAR MATRIX
  5. EXTRACELLULAR MATRIX IN DEVELOPMENTAL BIOLOGY
  6. EXTRACELLULAR MATRIX AS A SCAFFOLD FOR REGENERATIVE MEDICINE APPLICATIONS
  7. ECM BIOLOGIC SCAFFOLDS FOR REPAIR ESOPHAGEAL RECONSTRUCTION
  8. ECM FOR ORTHOPEDIC APPLICATIONS
  9. ECM BIOLOGIC SCAFFOLDS FOR URINARY TRACT RECONSTRUCTION
  10. ALTERNATIVE APPLICATIONS OF ECM BIOLOGIC SCAFFOLDS
  11. SUMMARY
  12. LITERATURE CITED

Extracellular matrix is the product of the resident cells of each tissue and organ and serves both structural and functional roles. The ECM exists in a state of dynamic equilibrium with its adjacent cell population and is responsive to ever changing environmental conditions and the functional demands of the cells and their parent tissue or organ (Bissell et al., 1986). The basic components of the ECM show a large degree of conservation among species with regard to molecular composition. Stated differently, the major structural proteins such as collagen, and the adhesive molecules including the glycosaminoglycans, proteoglycans, and glycoproteins, are remarkably similar in their basic amino acid structure and molecular structure between species. These similarities of composition and molecular structure belie the fundamental importance of the ECM to homeostasis and to the mechanisms by which mammalian tissues respond to injury. Structure relates to function; therefore, to understand the use of the ECM as a biologic scaffold for tissue reconstruction in regenerative medicine applications, it is important to understand the fundamental composition of mammalian ECM.

Collagen is the most abundant protein within the ECM. More than 20 distinct types of collagen have been identified and the most prevalent form found in mammalian tissues is type I collagen. Collagen has been well characterized and is ubiquitous across both the animal and plant kingdoms (van der Rest, 1992). Collagen has maintained a highly conserved amino acid sequence through the course of evolution and for this reason allogeneic and xenogeneic sources of type I collagen have been long recognized as effective biologic scaffolds for tissue repair with low antigenic potential. Bovine type I collagen is perhaps the most widely used biologic scaffold for therapeutic applications due to its abundant source and its history of successful use. Examples of the use of collagen as a scaffold for tissue repair include Zyplast, Contigen, Zyderm I and II, and the Collagen Meniscal Implant (CMI).

Collagen types other than type I exist in the native ECM, albeit in much lower quantities. These alternative collagen types each provide distinct mechanical and physical properties to the ECM and contribute to the utility of the intact ECM (as opposed to isolated components of the ECM) as a scaffold for tissue repair. By way of examples: type IV collagen is present within the basement membrane of all vascular structures and is an important ligand for endothelial cells, type VII collagen is the principal component of the anchoring fibrils of keratinocytes to the underlying basement membrane of the epidermis, and type VI collagen functions as a connector of functional proteins and glycosaminoglycans to larger structural proteins such as type I collagen, helping to provide a gel-like consistency to the ECM. Type III collagen exists within selected submucosal ECMs, such as the submucosal ECM of the urinary bladder, where nonrigid structure is demanded for appropriate function. This diversity of collagens within a single scaffold material is partially responsible for the distinctive biologic properties of the ECM when it is used as a scaffold for regenerative medicine applications and is exemplary of the difficulty in recreating such a composite scaffold material in vitro. In summary, the ECM is a rich source of numerous types of collagen and, perhaps more importantly, the ECM represents the gold standard for the optimal relative concentrations and orientation of these collagen types to each other, which provide an ideal environment for cell growth both in vitro and in vivo.

Fibronectin represents an important noncollagenous component of the ECM. Fibronectin exists both in soluble and tissue isoforms and possesses many desirable properties of a tissue repair scaffold, including ligands for adhesion of many cell types (Schwarzbauer, 1991; Miyamoto et al., 1998). In fact, this protein is the first example of a protein recognized to have dual functions, i.e., both structural and functional properties. Fibronectin exists within the ECM of both submucosal structures and basement membrane structures (McPherson and Badylak, 1998; Schwarzbauer, 1999). The fibronectin component of the ECM biologic scaffold materials derived from the porcine small intestinal submucosa (SIS) and porcine urinary bladder submucosa (UBS) has been shown to be partially responsible for the adhesion of endothelial cells during in vivo constructive remodeling of this xenogeneic bioscaffold (Hodde et al., 2002). The cell-friendly characteristics of this protein have made it an attractive ligand for use as a coating protein on various synthetic scaffold materials to promote host biocompatibility.

Laminin is a complex adhesion protein found within the ECM, especially within the basement membrane form of ECM (Schwarzbauer, 1999). This trimeric crosslinked polypeptide exists in numerous forms dependent on the particular mixture of peptide chains (e.g., α1, β1, γ1) (Timpl, 1996; Timpl and Brown, 1996). The prominent role of laminin in the formation and maintenance of vascular structures is particularly noteworthy when considering the ECM as a scaffold for tissue repair (Ponce et al., 1999; Werb et al., 1999). Vascularization of scaffolds for tissue repair is one of the rate-limiting steps in the field of regenerative medicine and proteins such as laminin are receiving close attention as an important component of scaffold materials with the intended clinical application of blood contact (e.g., vascular substitutes, cardiac repair scaffolds).

Glycosaminoglycans (GAGs) are important components of ECM and play important roles in the binding and preservation of growth factors and cytokines, water retention, and the gel properties of the ECM. The heparin binding properties of numerous cell surface receptors and of many growth factors (e.g., FGF family, VEGF) make the heparin-rich GAGs extremely desirable components of scaffolds for tissue repair. The GAG components of the SIS-ECM scaffold consist of the naturally occurring mixture of chondroitin sulfates A and B, heparin, heparan sulfate, and hyaluronic acid (Hodde et al., 1996). Hyaluronic acid has been extensively investigated as a scaffold for dermal reconstruction and articular surface repair. Commercial products composed of hyaluronic acid include Hyal-System (solution for intradermal administration) and Hyalgan (solution for intra-arcticular injection).

The composition of the ECM includes a variety of bioactive molecules admixed with the binding molecules such as decorin and biglycan. Although cytokines and growth factors are present within ECM in extremely small quantities, these molecules act as potent modulators of cell behavior. The list of growth factors that can be found with the ECM is extensive and includes VEGF, bFGF, EGF, transforming growth factor β (TGF-β), keratinocyte growth factor (KGF), hepatocyte growth factor (HGF), and platelet-derived growth factor (PDGF), among others. These factors tend to exist in multiple isoforms, each with a specific biologic activity. Purified forms of cytokines and growth factors and biologic peptides have been investigated in recent years as therapeutic means of encouraging blood vessel formation (vascular endothelial cell growth factor, VEGF), inhibiting blood vessel formation (angiostatin), inducing bone formation (bone morphogenetic protein, BMP), stimulating deposition of granulation tissue (platelet-derived growth factor, PDGF), and encouraging epithelialization of wounds (keratinocyte growth factor, KGF). However, the therapeutic approach of isolated growth factor delivery has struggled with determination of optimal dose, sustained and localized release of the growth factor at the desired site, and the inability to turn the factor on and off as needed during the course of tissue repair. An advantage of utilizing the ECM in its native state as a scaffold for tissue repair is the presence of all of the attendant growth factors (and their inhibitors) in the relative amounts that exist in nature and, perhaps most importantly, in their native three-dimensional ultrastructure.

The preceding paragraphs suggest that the ECM is a collection of component molecules, each with a specific structure and function. However, the distinction between structural and functional proteins is becoming increasingly blurred. Domain peptides of proteins originally thought to have purely structural properties have been identified and found to have significant and potent modulating effects on cell behavior. For example, the RGD peptide that promotes adhesion of numerous cell types was first identified in the fibronectin molecule (Pierschbacher and Ruoslahti, 1984; Yamada and Kennedy, 1984), a molecule originally described for its structural properties. Several other peptides have since been identified in dual-function proteins, including laminin, entactin, fibrinogen, types I and VI collagen, and vitronectin, among others (Humphries et al., 1991). If one considers the ECM to be a degradable, naturally occurring biologic scaffold for tissue engineering/regenerative medicine applications, then both the structural and the functional components of the ECM are transient due to the rapid rate of degradation of ECM scaffolds in vivo (Badylak et al., 1998; Rickey et al., 2000). It is reasonable, therefore, to consider ECM scaffolds as temporary controlled-release vehicles for naturally occurring growth factors.

In recent years, the intact ECM, harvested from a variety of tissues, has been used as a scaffold for regenerative medicine applications. It has been recognized that the unique combination of the ECM components and perhaps more importantly their three-dimensional presentation to host cells provides an extraordinarily favorable substrate for tissue repair and reconstruction. Much less consideration has been given to the importance of the ECM in normal mammalian organogenesis.

EXTRACELLULAR MATRIX IN DEVELOPMENTAL BIOLOGY

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. COMPOSITION OF EXTRACELLULAR MATRIX
  5. EXTRACELLULAR MATRIX IN DEVELOPMENTAL BIOLOGY
  6. EXTRACELLULAR MATRIX AS A SCAFFOLD FOR REGENERATIVE MEDICINE APPLICATIONS
  7. ECM BIOLOGIC SCAFFOLDS FOR REPAIR ESOPHAGEAL RECONSTRUCTION
  8. ECM FOR ORTHOPEDIC APPLICATIONS
  9. ECM BIOLOGIC SCAFFOLDS FOR URINARY TRACT RECONSTRUCTION
  10. ALTERNATIVE APPLICATIONS OF ECM BIOLOGIC SCAFFOLDS
  11. SUMMARY
  12. LITERATURE CITED

Remarkably little is known or understood about the role of ECM components in normal mammalian embryonic and fetal development. It is recognized that certain structural molecules appear at critical times during differentiation of the various germ layers but the actual function of these molecules in the overall process is unknown.

The extent of our knowledge is largely an extension of what is known from in vitro studies and from the reported effects of selected growth substrates on embryonic stem cell (ESC) differentiation patterns. Most collagen types cause differentiation of progenitor cell populations. It is common, therefore, to find little if any collagen in the ECM surrounding ESC populations. Fibronectin, on the other hand, has been shown to play a central role in the development of vascular structures and can be found at an early stage in developing embryos. In fact, targeted deletion of fibronectin in the murine embryo results in embryonic death with disruption of normal blood vessel and cardiovascular development. Fibronectin has also been found to be critical for the maintenance of hematopoietic stem cell activity ex vivo, which is another indication of the important role for this molecule in the support of the stem cell phenotype. The crucial role of the β1 integrin chain in mediating hematopoietic stem cell interactions with fibronectin has been firmly established (Fassler and Meyer, 1995; Hirsch et al., 1996; Potocnik et al., 2000). Loss of the β1 integrin receptors in mice results in intrapartum mortality. It is logical that regenerative medicine approaches for tissue reconstruction should investigate fibronectin as a bioscaffold component.

Another ECM protein that appears to play a critical role in developmental biology is the complex adhesion molecule laminin. Laminin can be found within basement membrane structures and is perhaps the best studied of the ECM protein found in ESC-derived embryoid bodies (Li et al., 2002). Laminin plays a prominent role in the formation and the maintenance of vascular structures and is among the first and most critical of the ECM components in the process of cell and tissue differentiation.

Hyaluronic acid (HA) has been extensively investigated as a scaffold for regenerative medicine applications. HA, like other glycosaminoglycans (GAGs), has strong heparin binding properties and plays a role in the binding of growth factors and cytokines, promotes water retention, and contributes to the gel properties of the extracellular matrix. Concentration of HA within the ECM is highest in fetal and newborn tissues and therefore tends to be associated with desirable healing properties. Processes that require cell migration such as morphogenesis, wound repair, and inflammation typically involve HA and its receptors (CD44 and receptor for hyaluronate-mediated motility, RHAMM) (Entwistle et al., 1995; Hodde et al., 1996).

In summary, if one considers the ECM to be a substrate for cell growth and differentiation, then it is reasonable to think of the ECM as a temporary controlled-release vehicle for naturally derived growth factors. As our understanding of the differences within the ECM derived from different tissues increases, our ability to modulate the remodeling process including the differentiation of progenitor cells in the ECM environment will improve.

EXTRACELLULAR MATRIX AS A SCAFFOLD FOR REGENERATIVE MEDICINE APPLICATIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. COMPOSITION OF EXTRACELLULAR MATRIX
  5. EXTRACELLULAR MATRIX IN DEVELOPMENTAL BIOLOGY
  6. EXTRACELLULAR MATRIX AS A SCAFFOLD FOR REGENERATIVE MEDICINE APPLICATIONS
  7. ECM BIOLOGIC SCAFFOLDS FOR REPAIR ESOPHAGEAL RECONSTRUCTION
  8. ECM FOR ORTHOPEDIC APPLICATIONS
  9. ECM BIOLOGIC SCAFFOLDS FOR URINARY TRACT RECONSTRUCTION
  10. ALTERNATIVE APPLICATIONS OF ECM BIOLOGIC SCAFFOLDS
  11. SUMMARY
  12. LITERATURE CITED

The ECM has been used as a scaffold for reconstruction of numerous tissues in both preclinical animal studies and in human clinical studies. The ECM has been used in many different forms, including sheets, particulate/powder form, or shaped in a variety of structures (e.g., tubes) appropriate for site-specific applications. The uniform features of the ECM include recruitment of host cells, degradation of the ECM scaffold itself, and replacement of the scaffold by new host-derived ECM. Subsequent self-assembly of the matrix, cellular differentiation and organization, and the formation of functional tissue depends on factors such as the microenvironment and mechanical forces applied to the site. The following paragraphs describe a few of the regenerative medicine applications of ECM scaffolds.

ECM BIOLOGIC SCAFFOLDS FOR REPAIR ESOPHAGEAL RECONSTRUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. COMPOSITION OF EXTRACELLULAR MATRIX
  5. EXTRACELLULAR MATRIX IN DEVELOPMENTAL BIOLOGY
  6. EXTRACELLULAR MATRIX AS A SCAFFOLD FOR REGENERATIVE MEDICINE APPLICATIONS
  7. ECM BIOLOGIC SCAFFOLDS FOR REPAIR ESOPHAGEAL RECONSTRUCTION
  8. ECM FOR ORTHOPEDIC APPLICATIONS
  9. ECM BIOLOGIC SCAFFOLDS FOR URINARY TRACT RECONSTRUCTION
  10. ALTERNATIVE APPLICATIONS OF ECM BIOLOGIC SCAFFOLDS
  11. SUMMARY
  12. LITERATURE CITED

Injury to esophageal tissues typically results in a healing response that results in scar tissue formation and subsequent stricture. Stated differently, the default mechanism of wound healing in the esophagus is by scar tissue formation rather than structural and functional reconstitution of normal esophageal tissue. Therefore, regenerative medicine approaches for the rebuilding of esophageal tissue address a clinical need that currently has no acceptable solution. Xenogeneic (i.e., porcine) extracellular matrix has been successfully used as a biologic scaffold for esophageal reconstruction in a dog model. Interestingly, when the ECM alone was used as a template for reconstruction for partial-circumference (< 50%) esophageal defects, the healing response showed organized layers of muscle, submucosal tissue, and an intact mucosal layer without stricture (Badylak et al., 2000). However, for full-circumferential replacement of the esophagus, the ECM alone healed with unacceptable stricture. By adding autologous muscle cells to the scaffold in situ, the healing response could be modulated to result in functional esophageal tissue with minimal stricture (Badylak et al., 2005). It appears that xenogeneic ECM has the ability to modulate the default wound healing response in the esophageal location and by combining appropriate populations of autologous cells with the extracellular matrix, a partial recapitulation of esophageal development can be induced.

ECM FOR ORTHOPEDIC APPLICATIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. COMPOSITION OF EXTRACELLULAR MATRIX
  5. EXTRACELLULAR MATRIX IN DEVELOPMENTAL BIOLOGY
  6. EXTRACELLULAR MATRIX AS A SCAFFOLD FOR REGENERATIVE MEDICINE APPLICATIONS
  7. ECM BIOLOGIC SCAFFOLDS FOR REPAIR ESOPHAGEAL RECONSTRUCTION
  8. ECM FOR ORTHOPEDIC APPLICATIONS
  9. ECM BIOLOGIC SCAFFOLDS FOR URINARY TRACT RECONSTRUCTION
  10. ALTERNATIVE APPLICATIONS OF ECM BIOLOGIC SCAFFOLDS
  11. SUMMARY
  12. LITERATURE CITED

Extracellular matrix has become a popular scaffold for reconstruction of musculotendinous structures. ECMs derived from the porcine small intestinal submucosa (Restore, CuffPatch), the human dermis ECM (GraftJacket, TissueMend), and other ECM sources are now commercially available for orthopedic surgical applications. Repair of the rotator cuff, Achilles tendon, and other orthopedic soft tissue structures has proven quite successful with the use of ECM biologic scaffolds in both preclinical and clinical studies (Badylak et al., 1998, 2002; Belcher and Zic, 2001; Dejardin et al., 2001; Harper, 2001; Beniker et al., 2003; MacLeod et al., 2003, 2004a, 2004b, 2005; Saray, 2003; Brigido et al., 2004; Cheung et al., 2004; Bano et al., 2005) (Fig. 2). It is important to note that the ECM scaffolds used for orthopedic applications merely represent a template that facilitates the deposition and self-assembly of new host-derived ECM and that the ultimate organization and tensile strength of the new musculotendinous tissue are dependent on extramural factors such as loading (rehabilitation).

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Figure 2. Focal area of tendon degeneration can be seen in the superficial digital flexor tendon of a 9-year-old mare (encircled area in left image). Following injection of 3 mL of the particulate form of the UBM-ECM biologic scaffold, the lesion showed almost complete resolution (right image) within 6 weeks. Ambulation returned to normal within 3 weeks.

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ECM BIOLOGIC SCAFFOLDS FOR URINARY TRACT RECONSTRUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. COMPOSITION OF EXTRACELLULAR MATRIX
  5. EXTRACELLULAR MATRIX IN DEVELOPMENTAL BIOLOGY
  6. EXTRACELLULAR MATRIX AS A SCAFFOLD FOR REGENERATIVE MEDICINE APPLICATIONS
  7. ECM BIOLOGIC SCAFFOLDS FOR REPAIR ESOPHAGEAL RECONSTRUCTION
  8. ECM FOR ORTHOPEDIC APPLICATIONS
  9. ECM BIOLOGIC SCAFFOLDS FOR URINARY TRACT RECONSTRUCTION
  10. ALTERNATIVE APPLICATIONS OF ECM BIOLOGIC SCAFFOLDS
  11. SUMMARY
  12. LITERATURE CITED

Reconstruction of the lower urinary tract has been one of the most widely used applications for biologic scaffolds derived from the extracellular matrix (Piechota et al., 1998a, 1998b, 1999; Atala, 2001b, 2001a, 2002, 2003). ECMs derived from the urinary bladder and SIS have been used to reconstruct the urethra, the vaginal wall, and in augmentation cystoplasty procedures. Vaginal sling procedures with ECM materials have proven very effective for the treatment of postmenopausal urinary incontinence. These scaffold materials promote a constructive remodeling with minimization of scar tissue. The use of the ECM scaffolds has provided an attractive alternative to the use of autologous intestinal tissue and synthetic materials in these surgical applications.

ALTERNATIVE APPLICATIONS OF ECM BIOLOGIC SCAFFOLDS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. COMPOSITION OF EXTRACELLULAR MATRIX
  5. EXTRACELLULAR MATRIX IN DEVELOPMENTAL BIOLOGY
  6. EXTRACELLULAR MATRIX AS A SCAFFOLD FOR REGENERATIVE MEDICINE APPLICATIONS
  7. ECM BIOLOGIC SCAFFOLDS FOR REPAIR ESOPHAGEAL RECONSTRUCTION
  8. ECM FOR ORTHOPEDIC APPLICATIONS
  9. ECM BIOLOGIC SCAFFOLDS FOR URINARY TRACT RECONSTRUCTION
  10. ALTERNATIVE APPLICATIONS OF ECM BIOLOGIC SCAFFOLDS
  11. SUMMARY
  12. LITERATURE CITED

In addition to the above-mentioned applications of the extracellular matrix as a scaffold for orthopedic, lower urinary tract, and esophageal reconstruction, the ECM has now been successfully used by investigators in the field of regenerative medicine for the repair and reconstruction of dermal structures, cardiovascular structures, central nervous system structures, and other surgical applications in hundreds of thousands of patients (Badylak et al., 1999, 2002; Badylak and Yoder, 2003; Badylak, 2004, 2005). Mechanisms by which the ECM facilitates constructive remodeling versus scar tissue formation are only beginning to be understood. It is recognized that maintaining the ECM and its three-dimensional ultrastructure results in a more favorable healing response than occurs when subjecting the ECM to harsh processing such as chemical crosslinking. Degradation of the ECM results in the rapid disappearance of the ECM and replacement by host cells and new matrix that self-assemble in a form that is usually structurally and functionally acceptable. It has recently been shown that degradation products of the ECM in themselves have biologic activity such as chemoattractant activity to endothelial cells and progenitor cells (Li et al., 2004). The ECM appears to be rich in signals that attract appropriate cell populations that participate in the rebuilding of tissues. The extent to which these processes mimic those that occur during developmental biology remains to be shown.

SUMMARY

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. COMPOSITION OF EXTRACELLULAR MATRIX
  5. EXTRACELLULAR MATRIX IN DEVELOPMENTAL BIOLOGY
  6. EXTRACELLULAR MATRIX AS A SCAFFOLD FOR REGENERATIVE MEDICINE APPLICATIONS
  7. ECM BIOLOGIC SCAFFOLDS FOR REPAIR ESOPHAGEAL RECONSTRUCTION
  8. ECM FOR ORTHOPEDIC APPLICATIONS
  9. ECM BIOLOGIC SCAFFOLDS FOR URINARY TRACT RECONSTRUCTION
  10. ALTERNATIVE APPLICATIONS OF ECM BIOLOGIC SCAFFOLDS
  11. SUMMARY
  12. LITERATURE CITED

In summary, the extracellular matrix represents Mother Nature's biologic scaffold. The ECM is rich in structural and functional proteins that not only maintain the health of differentiated tissues, but support the host response to tissue injury. These same molecules are present during fetal development and play an important role in tissue morphogenesis and organogenesis. The extent to which these processes overlap and can be manipulated is as yet unknown but offers a potentially valuable regenerative medicine approach for the replacement of damaged or missing tissues.

LITERATURE CITED

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. COMPOSITION OF EXTRACELLULAR MATRIX
  5. EXTRACELLULAR MATRIX IN DEVELOPMENTAL BIOLOGY
  6. EXTRACELLULAR MATRIX AS A SCAFFOLD FOR REGENERATIVE MEDICINE APPLICATIONS
  7. ECM BIOLOGIC SCAFFOLDS FOR REPAIR ESOPHAGEAL RECONSTRUCTION
  8. ECM FOR ORTHOPEDIC APPLICATIONS
  9. ECM BIOLOGIC SCAFFOLDS FOR URINARY TRACT RECONSTRUCTION
  10. ALTERNATIVE APPLICATIONS OF ECM BIOLOGIC SCAFFOLDS
  11. SUMMARY
  12. LITERATURE CITED