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Antonios G Mikos - One of the best experts on this subject based on the ideXlab platform.

  • oligo poly ethylene Glycol fumarate hydrogel enhances osteochondral repair in porcine femoral condyle defects
    Clinical Orthopaedics and Related Research, 2013
    Co-Authors: James H P Hui, Xiafei Ren, Mohd Hassan Afizah, Kerm Sin Chian, Antonios G Mikos
    Abstract:

    Background Management of osteochondritis dissecans remains a challenge. Use of oligo[poly(ethylene Glycol)fumarate] (OPF) hydrogel scaffold alone has been reported in osteochondral defect repair in small animal models. However, preclinical evaluation of usage of this scaffold alone as a treatment strategy is limited.

  • adapting biodegradable oligo poly ethylene Glycol fumarate hydrogels for pigment epithelial cell encapsulation and lens regeneration
    Tissue Engineering Part C-methods, 2010
    Co-Authors: Mimi W Zhang, Kenta Nakamura, H S Park, Xuan Guo, Robert M Raphael, Kurtis F Kasper, Antonios G Mikos, Panagiotis A. Tsonis
    Abstract:

    This study investigated the encapsulation of newt iris pigment epithelial cells (PECs), which have the ability to regenerate a lens by trans-differentiation in vivo, within a biodegradable hydrogel of oligo(poly(ethylene Glycol) fumarate) crosslinked with poly(ethylene Glycol)-diacrylate. Hydrogel beads of initial diameter of 1 mm were fabricated by a molding technique. The swelling ratio and degradation rate of the hydrogel beads decreased with increasing crosslinking ratios. Confocal microscopy confirmed the cytocompatibility of crosslinking hydrogel formulations as evidenced by the viability of an encapsulated model cell line within a crosslinked hydrogel bead. Hydrogel beads encapsulating iris PECs were also implanted into lentectomized newts in vivo; histological evaluation of explants after 30 days revealed a regenerated lens, thus demonstrating that the presence of degrading hydrogel did not adversely affect lens regeneration. The results of this study suggest the potential of a method for lens regeneration involving oligo(poly(ethylene Glycol) fumarate) hydrogels for iris PEC encapsulation and transplantation.

  • modulation of marrow stromal osteoblast adhesion on biomimetic oligo poly ethylene Glycol fumarate hydrogels modified with arg gly asp peptides and a poly ethylene Glycol spacer
    Journal of Biomedical Materials Research, 2002
    Co-Authors: Heungsoo Shin, Seongbong Jo, Antonios G Mikos
    Abstract:

    Novel oligo[poly(ethylene Glycol) fumarate] (OPF) hydrogels functionalized with cell adhesion peptides were prepared, and the effects of incorporated peptide density and macromolecular structure of hydrogels on attachment and morphology of marrow stromal cells (MSCs) were evaluated. Poly(ethylene Glycol) (PEG; number average molecular weight of 930, 2860, and 6090) was used to synthesize OPF. A model peptide, Gly-Arg-Gly-Asp (GRGD), was incorporated into OPF hydrogels after being coupled to acrylated PEG of molecular weight 3400. The increase of incorporated peptide concentration enhanced MSC attachment to OPF hydrogels of PEG of molecular weight of 930 and 2860. However, the number of attached MSCs to OPF hydrogels of PEG (molecular weight 6090) remained constant regardless of the peptide density. The length of PEG in OPF also influenced cell attachment. When 1 μmole peptide/g hydrogel was incorporated into the OPF hydrogels, the degree of cell attachment at 12 h relative to the initial seeding density was 93.9 ± 5.9%, 64.7 ± 8.2%, and 9.3 ± 6.6% for OPF hydrogels prepared with PEG of molecular weights of 930, 2860, and 6090, respectively. However, the crosslinking density of hydrogels did not significantly affect cell attachment. The interaction was sequence specific, in that MSC attachment to GRGD-modified hydrogels was competitively inhibited when cells were incubated in the presence of 0.5 mM soluble GRGD before cell seeding. These results suggest that we can modulate MSC attachment to OPF hydrogels by altering the peptide density and the molecular structure of OPF hydrogels. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 169–179, 2002

  • effect of poly ethylene Glycol molecular weight on tensile and swelling properties of oligo poly ethylene Glycol fumarate hydrogels for cartilage tissue engineering
    Journal of Biomedical Materials Research, 2002
    Co-Authors: Johnna S Temenoff, Kyriacos A Athanasiou, Richard G Lebaron, Antonios G Mikos
    Abstract:

    This study was designed to determine the effect of changes in poly(ethylene Glycol) (PEG) molecular weight on swelling and mechanical properties of hydrogels made from a novel polymer, oligo(poly(ethylene Glycol) fumarate) (OPF), recently developed in our laboratory. Properties of hydrogels made from OPF with initial PEG molecular weights of 860, 3900, and 9300 were examined. The PEG 3900 formulation had a tensile modulus of 23.1 +/- 12.4 kPa and percent elongation at fracture of 53.2 +/- 13.7%; the PEG 9300 formulation had similar tensile properties (modulus: 16.5 +/- 4.6 kPa, elongation: 76.0 +/- 26.4%). However, the PEG 860 gels had a significantly higher modulus (89.5 +/- 50.7 kPa) and a significantly smaller percent elongation at fracture (30.1 +/- 6.4%), when compared with other formulations. Additionally, there were significant differences in percent swelling between each of the formulations. Molecular weight between crosslinks (M(c)) and mesh size were calculated for each OPF formulation. M(c) increased from 2010 +/- 116 g/mol with PEG 860 to 6250 +/- 280 g/mol with PEG 9300. Mesh size calculations showed a similar trend (76 +/- 2 A for PEG 860 to 160 +/- 6 A for PEG 9300). It was also found that these hydrogels could be laminated if a second layer was added before the first had completely crosslinked. Mechanical testing of these laminated gels revealed that the presence of an interfacial area did not significantly alter their tensile properties. These results suggest that the material properties of OPF-based hydrogels can be altered by changing the molecular weight of PEG used in synthesis and that multilayered OPF hydrogel constructs can be produced, with each layer having distinct mechanical properties.

  • effect of poly ethylene Glycol molecular weight on tensile and swelling properties of oligo poly ethylene Glycol fumarate hydrogels for cartilage tissue engineering
    Journal of Biomedical Materials Research, 2002
    Co-Authors: Johnna S Temenoff, Kyriacos A Athanasiou, Richard G Lebaron, Antonios G Mikos
    Abstract:

    This study was designed to determine the effect of changes in poly(ethylene Glycol) (PEG) molecular weight on swelling and mechanical properties of hydrogels made from a novel polymer, oligo(poly(ethylene Glycol) fumarate) (OPF), recently developed in our laboratory. Properties of hydrogels made from OPF with initial PEG molecular weights of 860, 3900, and 9300 were examined. The PEG 3900 formulation had a tensile modulus of 23.1 ± 12.4 kPa and percent elongation at fracture of 53.2 ± 13.7%; the PEG 9300 formulation had similar tensile properties (modulus: 16.5 ± 4.6 kPa, elongation: 76.0 ± 26.4%). However, the PEG 860 gels had a significantly higher modulus (89.5 ± 50.7 kPa) and a significantly smaller percent elongation at fracture (30.1 ± 6.4%), when compared with other formulations. Additionally, there were significant differences in percent swelling between each of the formulations. Molecular weight between crosslinks (Mc) and mesh size were calculated for each OPF formulation. Mc increased from 2010 ± 116 g/mol with PEG 860 to 6250 ± 280 g/mol with PEG 9300. Mesh size calculations showed a similar trend (76 ± 2 A for PEG 860 to 160 ± 6 A for PEG 9300). It was also found that these hydrogels could be laminated if a second layer was added before the first had completely crosslinked. Mechanical testing of these laminated gels revealed that the presence of an interfacial area did not significantly alter their tensile properties. These results suggest that the material properties of OPF-based hydrogels can be altered by changing the molecular weight of PEG used in synthesis and that multilayered OPF hydrogel constructs can be produced, with each layer having distinct mechanical properties. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 429–437, 2002

Jeffrey A Hubbell - One of the best experts on this subject based on the ideXlab platform.

  • biologically engineered protein graft poly ethylene Glycol hydrogels a cell adhesive and plasmin degradable biosynthetic material for tissue repair
    Biomacromolecules, 2002
    Co-Authors: Sven Halstenberg, Alyssa Panitch, Heike Hall, Simone C Rizzi, Jeffrey A Hubbell
    Abstract:

    The goal of the research presented in this dissertation was to create a biomimetic artificial material that exhibits functions of extracellular matrix relevant for improved nerve regeneration. To identify minimal factors necessary for neurite extension in a suitable model system, neural adhesion peptides were photoimmobilized on highly crosslinked poly(ethylene Glycol)-based substrates that were otherwise non-adhesive. Neurons adhered in two-dimensional patterns for eleven hours, but no neurites extended. In contrast, human fibroblasts adhered and spread on regions with photoimmobilized RGDS oligopeptide, but not on RDGS peptide, suggesting that specific integrin-ligand binding accounted for fibroblast adhesion and spreading. To enable neurite extension and nerve regeneration in three dimensions, and to address the need for specifically cell adhesive and cell degradable materials for clinical applications in tissue repair in general, an artificial protein was recombinantly expressed and purified that consisted of a repeating amino acid sequence based on fibrinogen and antithrombin III. The artificial protein contained integrin-binding RGD sites, plasmin degradation sites, and heparin-binding sequences. Furthermore, the protein contained six cysteine residues as grafting sites for poly(ethylene Glycol) diacrylate via Michael-type conjugate addition. The resulting protein-graft-poly(ethylene Glycol)acrylates were crosslinked by photopolymerization to form hydrogels. Human fibroblasts attached to, invaded, and apparently proliferated in the artificial hydrogel matrices three-dimensionally. Fibroblast penetration was inhibited in a concentration-dependent manner by both soluble cyclo(RGDFV) peptide and aprotinin, a serine-protease inhibitor. Inhibition of fibroblast outgrowth by cyclic RGD peptide suggests that cellular integrins engaged in specific binding to RGD sites present in the artificial protein-graft-poly(ethylene Glycol) hydrogels' protein core. Inhibition by aprotinin suggests that serine protease-mediated cleavage of the hydrogel matrix was the mode of cellular ingrowth. Although three-dimensional ingrowth of fibroblasts into protein-graft-poly(ethylene Glycol) hydrogels occurred, only surface neurite outgrowth was observed from chick dorsal root ganglia. Neurite outgrowth depended on the concentration of matrix-bound heparin, suggesting that heparin was necessary to immobilize neuroactive adhesion- and/or growth factors in the hydrogels. Toward three-dimensional neurite outgrowth in protein-graft-poly(ethylene Glycol) hydrogels, additional heparin-binding factors can be identified or designed for intentional immobilization in future experiments. Together, the above results show that specific biological functions can be harnessed by protein-graft-poly(ethylene Glycol) hydrogels to serve as matrices for tissue repair and regeneration. In particular, the two design objectives, specific cell adhesion and degradability by cell-associated proteases, were fulfilled by the material. In the future, this and similar artificial protein-graft-poly(ethylene Glycol) materials with varying protein elements for improved wound healing might serve as biosynthetic implant materials or wound dressings that degrade in synchrony with the formation of a variety of target tissues.

  • Biologically engineered protein-graft-poly(ethylene Glycol) hydrogels: A cell adhesive and plasmin-degradable biosynthetic material for tissue repair
    Biomacromolecules, 2002
    Co-Authors: Sven Halstenberg, Simone Rizzi, Alyssa Panitch, Heike Hall, Jeffrey A Hubbell
    Abstract:

    To address the need for bioactive materials toward clinical applications in wound healing and tissue regeneration, an artificial protein was created by recombinant DNA methods and modified by grafting of poly(ethylene Glycol) diacrylate. Subsequent photopolymerization of the acrylate-containing precursors yielded protein-graft-poly(ethylene Glycol) hydrogels. The artificial protein contained repeating amino acid sequences based on fibrinogen and anti-thrombin III, comprising an RGD integrin-binding motif, two plasmin degradation sites, and a heparin-binding site. Two-dimensional adhesion studies showed that the artificial protein had specific integrin-binding capability based on the RGD motif contained in its fibrinogen-based sequence. Furthermore, heparin bound strongly to the protein's anti-thrombin III-based region. Protein-graft-poly(ethylene Glycol) hydrogels were plasmin degradable, had Young's moduli up to 3.5 kPa, and supported three-dimensional outgrowth of human fibroblasts. Cell attachment in three dimensions resulted from specific cell-surface integrin binding to the material's RGD sequence. Hydrogel penetration by cells involved serine-protease mediated matrix degradation in temporal and spatial synchrony with cellular outgrowth. Protein-graft-poly(ethylene Glycol) hydrogels represent a new and versatile class of biomimetic hybrid materials that hold clinical promise in serving as implants to promote wound healing and tissue regeneration.

Sophie Cantin - One of the best experts on this subject based on the ideXlab platform.

Sven Halstenberg - One of the best experts on this subject based on the ideXlab platform.

  • biologically engineered protein graft poly ethylene Glycol hydrogels a cell adhesive and plasmin degradable biosynthetic material for tissue repair
    Biomacromolecules, 2002
    Co-Authors: Sven Halstenberg, Alyssa Panitch, Heike Hall, Simone C Rizzi, Jeffrey A Hubbell
    Abstract:

    The goal of the research presented in this dissertation was to create a biomimetic artificial material that exhibits functions of extracellular matrix relevant for improved nerve regeneration. To identify minimal factors necessary for neurite extension in a suitable model system, neural adhesion peptides were photoimmobilized on highly crosslinked poly(ethylene Glycol)-based substrates that were otherwise non-adhesive. Neurons adhered in two-dimensional patterns for eleven hours, but no neurites extended. In contrast, human fibroblasts adhered and spread on regions with photoimmobilized RGDS oligopeptide, but not on RDGS peptide, suggesting that specific integrin-ligand binding accounted for fibroblast adhesion and spreading. To enable neurite extension and nerve regeneration in three dimensions, and to address the need for specifically cell adhesive and cell degradable materials for clinical applications in tissue repair in general, an artificial protein was recombinantly expressed and purified that consisted of a repeating amino acid sequence based on fibrinogen and antithrombin III. The artificial protein contained integrin-binding RGD sites, plasmin degradation sites, and heparin-binding sequences. Furthermore, the protein contained six cysteine residues as grafting sites for poly(ethylene Glycol) diacrylate via Michael-type conjugate addition. The resulting protein-graft-poly(ethylene Glycol)acrylates were crosslinked by photopolymerization to form hydrogels. Human fibroblasts attached to, invaded, and apparently proliferated in the artificial hydrogel matrices three-dimensionally. Fibroblast penetration was inhibited in a concentration-dependent manner by both soluble cyclo(RGDFV) peptide and aprotinin, a serine-protease inhibitor. Inhibition of fibroblast outgrowth by cyclic RGD peptide suggests that cellular integrins engaged in specific binding to RGD sites present in the artificial protein-graft-poly(ethylene Glycol) hydrogels' protein core. Inhibition by aprotinin suggests that serine protease-mediated cleavage of the hydrogel matrix was the mode of cellular ingrowth. Although three-dimensional ingrowth of fibroblasts into protein-graft-poly(ethylene Glycol) hydrogels occurred, only surface neurite outgrowth was observed from chick dorsal root ganglia. Neurite outgrowth depended on the concentration of matrix-bound heparin, suggesting that heparin was necessary to immobilize neuroactive adhesion- and/or growth factors in the hydrogels. Toward three-dimensional neurite outgrowth in protein-graft-poly(ethylene Glycol) hydrogels, additional heparin-binding factors can be identified or designed for intentional immobilization in future experiments. Together, the above results show that specific biological functions can be harnessed by protein-graft-poly(ethylene Glycol) hydrogels to serve as matrices for tissue repair and regeneration. In particular, the two design objectives, specific cell adhesion and degradability by cell-associated proteases, were fulfilled by the material. In the future, this and similar artificial protein-graft-poly(ethylene Glycol) materials with varying protein elements for improved wound healing might serve as biosynthetic implant materials or wound dressings that degrade in synchrony with the formation of a variety of target tissues.

  • Biologically engineered protein-graft-poly(ethylene Glycol) hydrogels: A cell adhesive and plasmin-degradable biosynthetic material for tissue repair
    Biomacromolecules, 2002
    Co-Authors: Sven Halstenberg, Simone Rizzi, Alyssa Panitch, Heike Hall, Jeffrey A Hubbell
    Abstract:

    To address the need for bioactive materials toward clinical applications in wound healing and tissue regeneration, an artificial protein was created by recombinant DNA methods and modified by grafting of poly(ethylene Glycol) diacrylate. Subsequent photopolymerization of the acrylate-containing precursors yielded protein-graft-poly(ethylene Glycol) hydrogels. The artificial protein contained repeating amino acid sequences based on fibrinogen and anti-thrombin III, comprising an RGD integrin-binding motif, two plasmin degradation sites, and a heparin-binding site. Two-dimensional adhesion studies showed that the artificial protein had specific integrin-binding capability based on the RGD motif contained in its fibrinogen-based sequence. Furthermore, heparin bound strongly to the protein's anti-thrombin III-based region. Protein-graft-poly(ethylene Glycol) hydrogels were plasmin degradable, had Young's moduli up to 3.5 kPa, and supported three-dimensional outgrowth of human fibroblasts. Cell attachment in three dimensions resulted from specific cell-surface integrin binding to the material's RGD sequence. Hydrogel penetration by cells involved serine-protease mediated matrix degradation in temporal and spatial synchrony with cellular outgrowth. Protein-graft-poly(ethylene Glycol) hydrogels represent a new and versatile class of biomimetic hybrid materials that hold clinical promise in serving as implants to promote wound healing and tissue regeneration.

Ellen H G Backus - One of the best experts on this subject based on the ideXlab platform.