Low-Molecular-Weight Peptides Derived from Extracellular Matrix as Chemoattractants for Primary Endothelial Cells

Abstract

The development of synthetic and naturally occurring scaffolds for tissue engineering applications has included strategies to promote attachment of specific cell types, control the rate of scaffold degradation, encourage angiogenesis, or otherwise modulate the host response. We have reported that bioscaffolds developed from porcine small intestinal submucosa (SIS) facilitate the constructive remodeling of tissues and recruit marrow-derived cells that persist long after the acute inflammatory stages have resolved. We have not yet determined which cells are recruited, the eventual fate of these cells, or via what mechanisms the events occur. We now have analyzed various molecular weight fractions of acid-hydrolyzed SIS by both functional and morphologic methods and have determined that fraction 4 (5 to 16 kDa) possesses chemoattractant activity for primary murine adult liver, heart, and kidney endothelial cells in vitro. Addition of fraction 4 to Matrigel plugs promoted in vivo vascularization when the plugs were implanted subcutaneously in mice. These results indicate that small-molecular-weight peptides derived from the degradation of porcine SIS are biologically active in the recruitment of murine endothelial cells in vitro and in vivo.

Epimorphic regeneration approach to tissue replacement in adult mammals

“…to such peptides in the form of defensins (40), cecropins (41,42), and magainins (43). Angiogenic and antiangiogenic activity has been shown to be caused by maticryptic peptides derived from a variety of collagen molecules (18,44). Peptides derived from extracellular matrix molecules have also been shown to modulate inflammation (45).…”

“…Although full characterization of these bioactive peptides has not been completed to date, ex vivo enzymatic, chemical, and physical methods (17)(18)(19), and in vivo physiologic methods (20), have generated a heterogeneous population of ECM peptides (13,21) with both chemotactic and mitogenic properties for a variety of stem and progenitor cells.…”

Comparison of Three Methods for the Derivation of a Biologic Scaffold Composed of Adipose Tissue Extracellular Matrix

“…Although the mechanisms by which these materials support and promote a constructive remodeling process are only partially understood, it appears clear that rapid degradation of the scaffold material with concurrent release of both intact growth factors and newly generated bioactive matricryptic peptides as well as the provision of unique surface architectures are factors that play an important role. [34][35][36][37][38][39][40][41] The ability to promote constructive remodeling in vivo has also been shown to be highly dependent on the methods used in preparing the scaffold material. 19,20,42 For example, chemical crosslinking is often used to increase the mechanical strength of a scaffold material, to slow degradation, or to mask cellular epitope that may remain within the scaffold material after decellularization.…”

Macrophage Participation in the Degradation and Remodeling of Extracellular Matrix Scaffolds

“…iologic scaffolds composed of extracellular matrix (ECM) can promote the constructive remodeling of injured tissues through mechanisms that include angiogenesis, [1][2][3][4][5] the recruitment of multipotential progenitor cells to the site of tissue reconstruction, [6][7][8][9] the release of antimicrobial peptides, [10][11][12][13][14][15] and activation of the alternative pathway of immunity. [16][17][18][19][20] There is convincing evidence that hostmediated degradation of ECM scaffolds is typically completed within 8-12 weeks and is necessary to realize the full beneficial effects of ECM-mediated tissue remodeling, [21][22][23] but the mechanisms by which such scaffold degradation occurs have been largely ignored.…”