Biomimetic hydrogels with pro-angiogenic properties

Abstract

To achieve the task of fabricating functional tissues, scaffold materials that can be sufficiently vascularized to mimic functionality and complexity of native tissues are yet to be developed. Here, we report development of synthetic, biomimetic hydrogels that allow the rapid formation of a stable and mature vascular network both in vitro and in vivo. Hydrogels were fabricated with integrin binding sites and protease-sensitive substrates to mimic the natural provisional extracellular matrices, and endothelial cells cultured in these hydrogels organized into stable, intricate network of capillarylike structures. The resulting structures were further stabilized by recruitment of mesenchymal progenitor cells that differentiated into smooth muscle cell lineage and deposited collagen IV and laminin in vitro. In addition, hydrogels transplanted into mouse cornea were infiltrated with host vasculature, resulting in extensive vascularization with functional blood vessels. These results indicate that these hydrogels may be useful for applications in basic biological research, tissue engineering, and regenerative medicine.

Integration and Regression of Implanted Engineered Human Vascular Networks During Deep Wound Healing

“…However, the inherent chemical and physical properties of these natural materials have limited their clinical usage [14,15]. Recent studies have explored synthetic materials as a xeno-free and more clinically relevant alternative for both therapeutic angiogenesis [16,17] and vascularization of tissue-engineered constructs [18,19]. We recently reported that hyaluronic acid (HA) hydrogels can be engineered to precisely control the generation of functional human vascular networks by ECFCs [20].…”

Recent Applications of Polymeric Biomaterials and Stem Cells in Tissue Engineering and Regenerative Medicine

“…165 Hydrogels were fabricated with integrin binding sites and protease-sensitive substrates to mimic the natural provisional ECM, and ECs cultured in these hydrogels organized into stable, intricate networks of capillary-like structures. The resulting structures were further stabilized by recruitment of mesenchymal progenitor cells that differentiated to a SMC lineage and deposited collagen IV and laminin.…”

Synthetic PEG Hydrogels as Extracellular Matrix Mimics for Tissue Engineering Applications

“…In addition, hydrolytic degradation is not representative of the cellularly mediated and dynamic process of proteolysis that takes place within the native ECM. Therefore, numerous studies have covalently incorporated peptide sequences susceptible to cleavage by cell-secreted proteases (i.e., plasmin-sensitive or MMPsensitive sequences) into PEG hydrogels thus manipulating gel degradation dynamically in response to cellularly mediated events (Gobin & West, 2002;Lee et al, 2007;Lutolf et al, 2003;Moon et al, 2007;Moon et al, 2010;Patterson & Hubbell 2010;Phelps et al, 2009;Seliktar et al, 2004;West & Hubbell, 1999;Zisch et al, 2003).…”

“…Studies using UV-based freeradical photopolymerization for the formation of MMP-sensitive, VEGF-bearing PEGDA hydrogels as potential matrices for the induction of vascularization indicated that endothelial cell tubule formation and maintenance was directly affected by gel mechanical properties. Hydrogels formed with an intermediate polymer weight percentage of 10% resulted in the formation of tubules, while less crosslinked PEGDA matrices (7.5% PEG content) caused complete tubule regression, and matrices (15% PEG content) reduced tubule formation in vitro (Moon et al, 2010). PEG hydrogels of this intermediate stiffness were implanted into mouse cornea using a micropocket angiogenesis assay and resulted in neovascularization in the presence of vascular endothelial growth factor (VEGF) (Rogers et al, 2007).…”