Synthetic MMP‐13 degradable ECMs based on poly(N‐isopropylacrylamide‐<i>co</i>‐acrylic acid) semi‐interpenetrating polymer networks. I. Degradation and cell migration

Kim, So Yeon; Chung, Eugene H.; Gilbert, Michele; Healy, Kevin E.

doi:10.1002/jbm.a.30375

Cited by 129 publications

(98 citation statements)

References 44 publications

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“…3A, B), were similar to the previously reported data. 26,30 The edsIPN had a lower |G*| at 228C than at 378C (Fig. 3A).…”

Section: Characterization Of the Edsipnsmentioning

confidence: 94%

“…2A). 25,26,30 The peptide crosslinker, Gln-Pro-Gln-Gly-Leu-Ala-Lys-NH 2 (QPQGLAK-NH 2 ; American Peptide, Sunnyvale, CA), was cleavable by matrix metalloproteinase (MMP)-13 and other collagenases, 30 and included a glutamine residue to promote solubility and a lysine residue to provide amine functional groups for modification. Reacting the peptide with acryloyl chloride in the presence of triethylamine generated amide linkages between the peptide and acrylic group, thereby introducing bifunctional acryl groups amenable to addition polymerization.…”

Section: Synthesis and Chemical Composition Of Edsipnsmentioning

confidence: 99%

“…[31][32][33] The poly(N-isopropylacrylamideco-acrylic acid) polymer network was interpenetrated by p(AAc)-graft-Ac-CGGNGEPRGDTYRAY-NH 2 [p(AAc)-g-RGD] linear polymer chains to promote cell adhesion. 26 Linear p(AAc) chains (MW 450,000; Polysciences; Warrington, PA) were first grafted with maleimide side groups, then the synthetic peptide, Ac-CGGNGEPRGDTYRAY-NH 2 derived from bone sialoprotein [bsp-RGD(15); American Peptide], was grafted to the maleimide side groups to produce and known angiogenic activity. [34][35][36] Further, bsp-RGD(15) has been shown to enhance the attachment of fibroblasts, 37 and associated integrin receptors have been implicated in the growth of both normal and myopic mammalian sclera.…”

Section: Synthesis and Chemical Composition Of Edsipnsmentioning

confidence: 99%

“…Previous studies indicated that this concentration was sufficient for cell adhesion, migration, and proliferation. 25,26,29 The grafted bsp-RGD(15) peptide chains have a statistical bulk distribution within the edsIPN, because the linear p(AAc) chains interpenetrate the synthetic network. 26,41 Electron microscopy imaging of edsIPN…”

Section: Determination Of Concentration Of Grafted Rgdmentioning

confidence: 99%

“…24 In this study, we used enzymatically degradable semiinterpenetrating polymer networks (edsIPNs) composed of poly(N-isopropylacrylamide-co-acrylic acid) with proteolytically degradable peptide crosslinkers and physically entangled peptide-functionalized linear poly (acrylic acid) [p(AAc)] chains that interpenetrate the synthetic hydrogel matrix. 25,26 Enzymatically degradable hydrogels, used as biomimetic extracellular matrix (ECM), have been reported to support human embryonic stem-cell selfrenewal, 27 act as vehicles for cell transplantation by sustaining early cellular remodeling and growth, 28 aid myocardium regeneration, 29 and promote mesenchymal stem-cell proliferation and bone formation in vivo. 25 Based on the known biochemistry of the fibrous sclera and characterization of various edsIPNs, one formulation was selected for evaluation.…”

Section: Introductionmentioning

confidence: 99%

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Scleral Reinforcement Through Host Tissue Integration with Biomimetic Enzymatically Degradable Semi-Interpenetrating Polymer Network

Wall

Healy

et al. 2010

Tissue Engineering Part A

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Enzymatically degradable semi-interpenetrating polymer networks (edsIPNs) were explored for their biocompatibility and ability to promote new scleral tissue growth, as a means of reinforcing the posterior wall of the eye. The edsIPNs comprised thermoresponsive poly(N-isopropylacrylamide-co-acrylic acid), customizable peptide crosslinkers cleavable by matrix metalloproteinases, and interpenetrating linear poly(acrylic acid)-graftpeptide chains to engage with cell surface receptors. Rheological studies revealed an increase in stiffness at body temperature; the complex shear modulus |G*| was 14.13 AE 6.13 Pa at 228C and 63.18 AE 12.24 Pa at 378C, compatible with injection at room temperature. Primary chick scleral fibroblasts and chondrocytes cultured on edsIPN increased by 15.1-and 11.1-fold, respectively, over 11 days; both exhibited delayed onset of exponential growth compared with the cells plated on tissue culture polystyrene. The edsIPN was delivered by retrobulbar injection (100 mL) to nine 2-week-old chicks to assess biocompatibility in vivo. Ocular axial dimensions were assessed using A-scan ultrasonography over 28 days, after which eyes were processed for histological analysis. Although edsIPN injections did not affect the rate of ocular elongation, the outer fibrous sclera showed significant thickening. The demonstration that injectable biomimetic edsIPNs stimulate scleral fibrous tissue growth represents proof-of-principle for a novel approach for scleral reinforcement and a potential therapy for high myopia.

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“…3A, B), were similar to the previously reported data. 26,30 The edsIPN had a lower |G*| at 228C than at 378C (Fig. 3A).…”

Section: Characterization Of the Edsipnsmentioning

confidence: 94%

Section: Synthesis and Chemical Composition Of Edsipnsmentioning

confidence: 99%

Section: Synthesis and Chemical Composition Of Edsipnsmentioning

confidence: 99%

Section: Determination Of Concentration Of Grafted Rgdmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Scleral Reinforcement Through Host Tissue Integration with Biomimetic Enzymatically Degradable Semi-Interpenetrating Polymer Network

Wall

Healy

et al. 2010

Tissue Engineering Part A

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Soft Tissue Scaffolds

Guan

Stankus

Wagner

2006

Wiley Encyclopedia of Biomedical Engineering

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The effort to develop soft tissues is one of the most demanding and challenging applications in tissue engineering. Soft tissues such as myocardium, blood vessels, skeletal muscle, adipose tissue, and even cartilage often possess large volumes, have high cell densities, and can be mechanically active. 3‐D scaffolds that match the mechanical properties of the tissue that they are replacing are preferred for soft tissue engineering, because such materials might transmit mechanical forces to the developing tissue during in vitro or in vivo development. A well‐defined biodegradation rate is ideal so that host tissue can replace the scaffold and that stress can be transferred from the support scaffold to the new tissue over an appropriate time period. The scaffolds not only serve as a structural support, but also can play an important role in facilitating cell adhesion, growth, and vascularization throughout the scaffold both during in vitro cell culture and in vivo tissue regeneration. Currently used materials meeting these criteria are diverse and include entirely synthetic materials as well as those that are derived from natural sources, and formats that are continuous on a microscale (hydrogels) and those that have defined microporous architectures. Although natural materials have the inherent advantage of bioactivity, they also possess limitations when employed as soft tissue scaffolds that may be overcome with synthetics. Some limitations associated with natural materials include inducement of an immune response that can lead to rapid degradation as well as poor batch‐to‐batch consistencies. Synthetic polymers permit better control over chemical and physical properties leading to tunability in mechanical strength and degradation rate. Surface properties of synthetic materials can also be more easily modified for improved cell attachment or migration. Some disadvantages of synthetic tissue scaffolds consist of potential toxic degradation products and undesired inflammatory responses. In addition, fabrication methods can process materials into scaffolds of desired porosity, morphologies, and anisotropies. The focus of this article will provide a brief overview of the scaffold preparation, properties, and applications of soft tissue scaffolds.

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