PARK CITY, UT, United States
PARK CITY, UT, United States

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Liu Y.,Chongqing Medical University | Liu Y.,Schepens Eye Research Institute | Wang R.,Schepens Eye Research Institute | Zarembinski T.I.,Glycosan Biosystems, Inc. | And 5 more authors.
Tissue Engineering - Part A | Year: 2013

Control of retinal progenitor cell (RPC) survival, delivery, and differentiation following transplantation into the retina remains a challenge. This is largely due to the use of culture systems that involve poorly defined animal products and do not mimic the natural developmental milieu. We describe the use of hyaluronic acid (HA) based hydrogels to encapsulate mouse RPCs and a delivery system for injectable tissue engineering. We selected HA because of its role in early development and as a feeder layer in stem cell cultures, and the relative ease with which various parameters can be controlled (e.g., hydrogel architecture, mechanics, and degradation). When encapsulated in three-dimensional HA hydrogels, RPCs maintained their undifferentiated state and readily formed neurospheres. These hydrogels were viscous solutions, exhibiting properties ideal for delivery to a subretinal space. The transplants caused very little disruption to the host retinal architecture. Hydrogels were completely degraded and RPCs distributed evenly in the subretinal space by week 3 and expressed the mature photoreceptor marker recoverin. HA hydrogels, with their developmentally relevant composition and malleable physical properties, provide a unique microenvironment for self renewal and differentiation of RPCs for retinal repair. © Mary Ann Liebert, Inc.


Horkay F.,U.S. National Institutes of Health | Magda J.,University of Utah | Alcoutlabi M.,University of Utah | Atzet S.,Glycosan Biosystems, Inc. | Zarembinski T.,Glycosan Biosystems, Inc.
Polymer | Year: 2010

The osmotic and scattering properties of hyaluronan-based composite hydrogels composed of stiff biopolymer chains (carboxymethylated thiolated hyaluronan (CMHA-S)) crosslinked by a flexible polymer (polyethylene glycol diacrylate (PEGDA)) are investigated and analyzed in terms of the scaling theory. The total pre-gel polymer weight concentration is varied between 0.5. wt.% and 3.2. wt.%, while the mole ratio between the reactive PEG chain ends and the thiolated HA moieties is changed between 0.15 and 1.0. The shear modulus G of the fully-swollen gels exhibits a stronger dependence on pre-gel concentration than on the crosslink density. Osmotic deswelling measurements reveal that the osmotic mixing pressure depends on the weight ratio CMHA-S/PEGDA, and is practically unaffected by the pre-gel concentration. Small-angle neutron scattering observations indicate that the thermodynamic properties of these composite gels are governed by total polymer concentration, i.e., specific interactions between the two polymeric components do not play a significant role. © 2010 Elsevier Ltd.


Trademark
Biotime, Inc., Orthocyte Corporation and Glycosan Biosystems, Inc. | Date: 2010-11-16

Cell culture media, cell scaffold hydrogel for medical research or scientific research use; kit primarily containing thiol-modified hyaluronan, thiol modified gelatin and polyethylene glycol diacrylate for medical research or scientific research use.


Trademark
Biotime, Inc., Orthocyte Corporation and Glycosan Biosystems, Inc. | Date: 2011-03-08

Thiol-modified hyaluronan for culturing mammalian cells for medical research or scientific research use.


Trademark
Biotime, Inc., Orthocyte Corporation and Glycosan Biosystems, Inc. | Date: 2010-11-16

Thiol-modified hyaluronan for medical research or scientific research use; kit primarily containing thiol-modified hyaluronan for medical research or scientific research use.


Trademark
Biotime, Inc., Orthocyte Corporation and Glycosan Biosystems, Inc. | Date: 2010-11-16

Thiol-modified hyaluronan and thiol-modified heparin for medical research or scientific research use.


Trademark
Biotime, Inc., Orthocyte Corporation and Glycosan Biosystems, Inc. | Date: 2010-11-16

Thiol-modified gelatin for medical research or scientific research use.


Trademark
Biotime, Inc., Orthocyte Corporation and Glycosan Biosystems, Inc. | Date: 2010-11-16

Thiol-reactive crosslinker, namely, polyethylene glycol diacrylate for medical research or scientific research use.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 106.85K | Year: 2010

DESCRIPTION (provided by applicant): An unmet need for expansion of primary cells and progenitor cells in three dimensions (3-D) is an extracellular matrix (ECM) substitute with user-controllable composition and compliance to which ECM proteins or synthetic peptides can be covalently attached by the end user. Glycosan BioSystems currently markets HyStem, an in situ-crosslinkable, semi-synthetic ECM composed of poly(ethylene glycol) diacrylate (PEGDA) and crosslinked thiol-modified hyaluronan (Glycosil) for culture of a variety of pluripotent cell types. The elastic modulus of the matrix determines to a large extent cell fate, and can be varied by changing crosslink density and concentration. In Phase I we will test the feasibility of a simple system for attachment of proteins to the hydrogels that would permit any synthetic polypeptide or any native matricellular protein (MP) to be covalently attached to the thiol-modified HA component of HyStem. In contrast to adding native ECM proteins that are not bound to the gel, and thus cannot provide mechanical support, this approach directly couples the pull of the cells on the proteins to the elastic modulus of the gel. We will compare MP-attached gels with the gelatin-containing HyStem-C hydrogel to identify conditions that maintain quiescence of mesenchymal stem cell (MSC) and that improve MSC differentiation capacity into adipocytes. Following the optimization of protein attachment conditions, we will determine the feasibility of this approach for growing MSCs in or on HyStem- MP hydrogels as autologous, animal-free feeder layers for the culturing of CD34+ stem cells derived from bone marrow. PUBLIC HEALTH RELEVANCE: An unmet need for expansion of primary cells and progenitor cells in three dimensions (3-D) is an extracellular matrix (ECM) substitute with user-controllable composition and compliance to which ECM proteins or synthetic peptides can be covalently attached by the end user. Glycosan BioSystems currently markets HyStem , an in situ-crosslinkable, semi-synthetic ECM composed of poly(ethylene glycol) diacrylate (PEGDA) and crosslinked thiol-modified hyaluronan (Glycosil ) for culture of a variety of pluripotent cell types. The goal of this proposal is to test the feasibility of a simple system for covalent attachment of extracellular matrix proteins to the HyStem hydrogel and to tailor the protein composition and stiffness for modulating the quiescence or differentiation of human mesenchymal stem cells.

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