Synthetic Mimics of the Extracellular Matrix: How Simple is Complex Enough?

Kyburz, Kyle A.; Anseth, Kristi S.

doi:10.1007/s10439-015-1297-4

Cited by 157 publications

(127 citation statements)

References 58 publications

(72 reference statements)

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“…At the opposite extreme, minimalistic approaches are parsimoniously incorporating features of ECM proteins such as RGD (integrin-binding) peptides or mimics in artificial scaffolds. However, proteomic studies have revealed that the ECMs of tissues are made of 150+ proteins and although reconstructing this complexity may be difficult (and perhaps unnecessary [96]), we propose that the results of proteomics studies aimed at characterizing in vivo ECMs should be exploited to guide the design of the next generation of bio-inspired scaffolds to support organ regeneration.…”

Section: Introductionmentioning

confidence: 99%

The extracellular matrix: Tools and insights for the “omics” era

et al. 2016

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The extracellular matrix (ECM) is a fundamental component of multicellular organisms that provides mechanical and chemical cues that orchestrate cellular and tissue organization and functions. Degradation, hyperproduction or alteration of the composition of the ECM cause or accompany numerous pathologies. Thus, a better characterization of ECM composition, metabolism, and biology can lead to the identification of novel prognostic and diagnostic markers and therapeutic opportunities. The development over the last few years of high-throughput (“omics”) approaches has considerably accelerated the pace of discovery in life sciences. In this review, we describe new bioinformatic tools and experimental strategies for ECM research, and illustrate how these tools and approaches can be exploited to provide novel insights in our understanding of ECM biology. We also introduce a web platform “the matrisome project” and the database MatrisomeDB that compiles in silico and in vivo data on the matrisome, defined as the ensemble of genes encoding ECM and ECM-associated proteins. Finally, we present a first draft of an ECM atlas built by compiling proteomics data on the ECM composition of 14 different tissues and tumor types.

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Section: Introductionmentioning

confidence: 99%

The extracellular matrix: Tools and insights for the “omics” era

et al. 2016

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“…30–33 Yang et al reported the conjugation of dexamethasone to a cysteine-containing MMP-sensitive peptide that was co-polymerized into PEG-based thiol-ene networks with encapsulated MSCs. 34 A dexamethasone derivative retaining part of the conjugated peptide was released in a cell-mediated manner and stimulated significant increases alkaline phosphatase activity and calcium deposition of encapsulated hMSCs.…”

Section: Introductionmentioning

confidence: 99%

Cell-Mediated Dexamethasone Release from Semi-IPNs Stimulates Osteogenic Differentiation of Encapsulated Mesenchymal Stem Cells

Bae

Lee

et al. 2015

Biomacromolecules

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Scaffold-based delivery of bioactive molecules capable of directing stem cell differentiation is critical to the development of point-of-care cell therapy for orthopaedic repair. Dexamethasone-conjugated hyaluronic acid (HA-DXM) was synthesized and combined with hydrolytically degradable, photocrosslinkable PEG-bis-(2-acryloyloxy propanoate) (PEG-bis-AP) to form semi-IPNs. Dexamethasone (DX) release was limited in physiological buffer and substantially increased in the presence of encapsulated human mesenchymal stem cells (hMSCs) or exogenous hyaluronidase, confirming that release occurred primarily by a cell-mediated enzymatic mechanism. hMSCs encapsulated in PEG-bis-AP/HA-DXM semi-IPNs increased osteoblast-specific gene expression, alkaline phosphatase activity, and matrix mineralization, attaining levels that were not significantly different from positive controls consisting of hMSCs in PEG-bis-AP/native HA cultured with DX supplementation in the culture medium. These studies demonstrate that PEG-bis-AP/HA-DXM semi-IPNs can provide cell-mediated release of bioactive free DX that induces hMSC osteogenic differentiation. This approach offers an efficient system for local delivery of osteogenic molecules empowering point of care applications.

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“…As well as providing mechanical support, many of these ECM components also play critical roles in cell signalling and cell adhesion processes that modulate cell behaviour 20 . To ensure artificial scaffolds provide an effective platform for TE, it is critical that they replicate both the structural and functional roles exhibited by the natural ECM 21,22 . Additionally, TE biomaterials must be biocompatible, and induce minimal immunogenic or fibrotic response upon implantation 23,24 .…”

Section: Introduction: the Tissue Engineering Imperativementioning

confidence: 99%

Tissue engineering with gellan gum

et al. 2016

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Engineering complex tissues for research and clinical applications relies on high-performance biomaterials that are amenable to biofabrication, maintain mechanical integrity, support specific cell behaviours, and, ultimately, biodegrade. In most cases, complex tissues will need to be fabricated from not one, but many biomaterials, which collectively fulfill these demanding requirements. Gellan gum is an anionic polysaccharide with potential to fill several key roles in engineered tissues, particularly after modification and blending. This review focuses on the present state of research into gellan gum, from its origins, purification and modification, through processing and biofabrication options, to its performance as a cell scaffold for both soft tissue and load bearing applications. Overall, we find gellan gum to be a highly versatile backbone material for tissue engineering research, upon which a broad array of form and functionality can be built. Disciplines Engineering | Physical Sciences and Mathematics Publication DetailsStevens, L. R., Gilmore, K. J., Wallace, G. Engineering complex tissues for research and clinical applications relies on high-performance biomaterials that are amenable to biofabrication, maintain mechanical integrity, support specific cell behaviours, and, ultimately, biodegrade. In most cases, complex tissues will need to be fabricated from not one, but many biomaterials, which collectively fulfill these demanding requirements. Gellan gum is an anionic polysaccharide with potential to fill several key roles in engineered tissues, particularly after modification and blending. This review focuses on the present state of research into gellan gum, from its origins, purification and modification, through processing and biofabrication options, to its performance as a cell scaffold for both soft tissue and load bearing applications. Overall, we find gellan gum to be a highly versatile backbone material for tissue engineering research, upon which a broad array of form and functionality can be built.

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Synthetic Mimics of the Extracellular Matrix: How Simple is Complex Enough?

Cited by 157 publications

References 58 publications

The extracellular matrix: Tools and insights for the “omics” era

The extracellular matrix: Tools and insights for the “omics” era

Cell-Mediated Dexamethasone Release from Semi-IPNs Stimulates Osteogenic Differentiation of Encapsulated Mesenchymal Stem Cells

Tissue engineering with gellan gum

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