Journal
BIOMATERIALS
Volume 89, Issue -, Pages 136-147Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.02.023
Keywords
Stem cell transplantation; Hyaluronic acid hydrogel; Growth factor sequestration; Neovascularization; MMP cleavable peptide; TGF beta 1
Funding
- National Heart Lung and Blood Institute of the National Institutes of Health [R01HL096525]
- Siebel Stem Cell Institute Postdoctoral Fellowship
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A critical design parameter for the function of synthetic extracellular matrices is to synchronize the gradual cell-mediated degradation of the matrix with the endogenous secretion of natural extracellular matrix (ECM) (e.g., creeping substitution). In hyaluronic acid (HyA)-based hydrogel matrices, we have investigated the effects of peptide crosslinkers with different matrix metalloproteinases (MMP) sensitivities on network degradation and neovascularization in vivo. The HyA hydrogel matrices consisted of cell adhesive peptides, heparin for both the presentation of exogenous and sequestration of endogenously synthesized growth factors, and MMP cleavable peptide linkages (i.e., QPQGLAK, GPLGMHGK, and GPLGLSLGK). Sca1(+)/CD45(-)/CD34(+)/CD44(+) cardiac progenitor cells (CPCs) cultured in the matrices with the slowly degradable QPQGLAK hydrogels supported the highest production of MMP-2, MMP-9, MMP-13, VEGF(165), and a range of angiogenesis related proteins. Hydrogels with QPQGLAK crosslinlcs supported prolonged retention of these proteins via heparin within the matrix, stimulating rapid vascular development, and anastomosis with the host vasculature when implanted in the murine hindlimb. (C) 2016 Elsevier Ltd. All rights reserved.
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