MMP-sensitive PEG hydrogel modified with RGD promotes bFGF, VEGF and EPC-mediated angiogenesis

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Abstract

Traumatic soft tissue defects such as bedsores, chronic skin ulcers, limb necrosis, osteonecrosis and other ischemic orthopedic diseases are the most clinically intractable and common problems in orthopedics due to unsatisfactory conventional treatments. The present study designed poly(ethylene glycol; PEG) hydrogels with covalently binded arginylglycylaspartic acid (RGD). Endothelial progenitor cells (EPCs) were encapsulated in the modified hydrogel along with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Results demonstrated that the modified hydrogel displayed good mechanical properties appropriate for a sustained release carrier. RGD modification significantly promoted EPC biocompatibility. VEGF and bFGF encapsulation enhanced the adhesion of EPCs, promoted the production of extracellular matrix and facilitated EPC proliferation. In addition, bFGF and VEGF induced angiogenesis. The combination of growth factors and EPCs in the hydrogel displayed a strong synergy to improve biocompatibility. The present results provided a potential novel treatment approach for soft tissue defects such as bone exposure, chronic skin ulcers, bedsores, limb necrosis, osteonecrosis and other ischemic diseases.

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Polymeric system for dual growth factor delivery.

T P Richardson, M C Peters, A B Ennett … (2001)

The development of tissues and organs is typically driven by the action of a number of growth factors. However, efforts to regenerate tissues (e.g., bone, blood vessels) typically rely on the delivery of single factors, and this may partially explain the limited clinical utility of many current approaches. One constraint on delivering appropriate combinations of factors is a lack of delivery vehicles that allow for a localized and controlled delivery of more than a single factor. We report a new polymeric system that allows for the tissue-specific delivery of two or more growth factors, with controlled dose and rate of delivery. The utility of this system was investigated in the context of therapeutic angiogenesis. We now demonstrate that dual delivery of vascular endothelial growth factor (VEGF)-165 and platelet-derived growth factor (PDGF)-BB, each with distinct kinetics, from a single, structural polymer scaffold results in the rapid formation of a mature vascular network. This is the first report of a vehicle capable of delivery of multiple angiogenic factors with distinct kinetics, and these results clearly indicate the importance of multiple growth factor action in tissue regeneration and engineering.

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Critical reevaluation of endothelial progenitor cell phenotypes for therapeutic and diagnostic use.

Gian Paolo Fadini, Douglas W. Losordo, Stefanie Dimmeler (2012)

Diverse subsets of endothelial progenitor cells (EPCs) are used for the treatment of ischemic diseases in clinical trials, and circulating EPCs levels are considered as biomarkers for coronary and peripheral artery disease. However, despite significant steps forward in defining their potential for both therapeutic and diagnostic purposes, further progress has been mired by unresolved questions around the definition and the mechanism of action of EPCs. Diverse culturing methods and detection of various combinations of different surface antigens were used to enrich and identify EPCs. These attempts were particularly challenged by the close relationship and overlapping markers of the endothelial and hematopoietic lineages. This article will critically review the most commonly used protocols to define EPCs by culture assays or by fluorescence-activated cell sorter in the context of their therapeutic or diagnostic use. We also delineate new research avenues to move forward our knowledge on EPC biology.

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Synthesis and physicochemical characterization of end-linked poly(ethylene glycol)-co-peptide hydrogels formed by Michael-type addition.

M. P. Lutolf, J Hubbell (2015)

The synthesis of novel hybrid hydrogels by stepwise copolymerization of multiarm vinyl sulfone-terminated poly(ethylene glycol) macromers and alpha-omega cysteine oligopeptides via Michael-type additions is described. Cross-linking kinetics, studied by in situ rheometry, can be controlled by pH and the presence of charged amino acid residues in close proximity to the Cys, which modulates the pK(a) of the thiol group. These end-linked networks were characterized by their equilibrium swelling in water, by their viscoelastic properties in the swollen state, and by their soluble fraction. It was demonstrated that structure and properties are very sensitive to the preparation state including stoichiometry and precursor concentration and less sensitive to the pH during cross-linking. For each network the concentration of elastically active chains (nu) was calculated from experimentally determined sol fractions using Miller-Macosko theory and compared to values obtained from swelling and rheometry studies and by calculation from Flory's classical network models. Hydrogels were also prepared with varying macromer structures, and their properties were shown to respond to both macromer functionality and molecular weight.

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Author and article information

Journal

Journal ID (nlm-ta): Exp Ther Med

Journal ID (iso-abbrev): Exp Ther Med

Journal ID (publisher-id): ETM

Title: Experimental and Therapeutic Medicine

Publisher: D.A. Spandidos

ISSN (Print): 1792-0981

ISSN (Electronic): 1792-1015

Publication date (Print): October 2019

Publication date (Electronic): 13 August 2019

Publication date PMC-release: 13 August 2019

Volume: 18

Issue: 4

Pages: 2933-2941

Affiliations

Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China

Author notes

Correspondence to: Dr Deyu Duan, Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, Hubei 430022, P.R. China, E-mail: deyuduan@ 123456yeah.net

Article

Publisher ID: ETM-0-0-7885

DOI: 10.3892/etm.2019.7885

PMC ID: 6755480

PubMed ID: 31572536

SO-VID: d1f959f1-31e4-4acc-b918-b286099532d7

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This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

MMP-sensitive PEG hydrogel modified with RGD promotes bFGF, VEGF and EPC-mediated angiogenesis

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Sex and gender-sensitive medicine

Most cited references 40

Polymeric system for dual growth factor delivery.

Critical reevaluation of endothelial progenitor cell phenotypes for therapeutic and diagnostic use.

Synthesis and physicochemical characterization of end-linked poly(ethylene glycol)-co-peptide hydrogels formed by Michael-type addition.

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