Leach JB and Schmidt CE: ‘Characterization of protein release from photocrosslinkable hyaluronic acid-polyethylene glycol hydrogel tissue engineering scaffolds’, Biomaterials, , 26

Department of Chemical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
Biomaterials (Impact Factor: 8.31). 01/2005; 26(2):125-35. DOI: 10.1016/j.biomaterials.2004.02.018
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ABSTRACT The goal of this work was to utilize the naturally derived bioactive polymer hyaluronic acid (HA) to create a combination tissue engineering scaffold and protein delivery device. HA is a non-immunogenic, non-adhesive glycosaminoglycan that plays significant roles in several cellular processes, including angiogenesis and the regulation of inflammation. In previous work, we created photopolymerizable glycidyl methacrylate-hyaluronic acid (GMHA) hydrogels that had controlled degradation rates, were cytocompatible, and were able to be modified with peptide moieties. In the present studies, we characterized the release of a model protein, bovine serum albumin (BSA), from GMHA and GMHA-polyethylene glycol (PEG) hydrogels. Although BSA could be released rapidly (> 60% within 6 h) from 1% GMHA hydrogels, we found that increasing either the GMHA or the PEG concentrations could lengthen the duration of protein delivery. Preliminary size exclusion chromatography studies indicated that the released BSA was almost entirely in its native monomeric form. Lastly, protein release was extended to several weeks by suspending BSA-poly(lactic-co-glycolic acid) microspheres within the hydrogel bulk. These initial studies indicate that the naturally derived biopolymer HA can be employed to design novel photopolymerizable composites that are suitable for delivering stable proteins from scaffolding in tissue engineering applications.

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    • "Hydrogels have been known to be effective carriers of drugs for cell-based drug delivery applications (Schmidt et al. 2008). One such representative is a hydrogel with Hyaluronic acid-based (HA) hydrogels which was specifically designed for the regeneration of different types of tissues (Leach and Schmidt 2005). TaO x can be cross-linked with the HA hydrogel to create a composite that can be used for efficient cell or drug delivery, where TaO x acts as the contrast agent allowing to monitor biodistribution and half-life of bioactive compartments. "
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    ABSTRACT: For centuries, inflammatory/foreign body reactions have plagued the attempts of clinicians to use metals for tissue and bone reconstructions. Since corrosion contributes to the rejection of metal by the body, an extremely bioinert metal - tantalum - has been successfully used in medicine. The outstanding biocompatibility and flexibility of tantalum established the basis for a growing cadre of clinical applications. One important application which benefited from the introduction of powder (particle) metallurgy is use of tantalum as bone implants. Porous materials have re-shaped the landscape of bone implants, as they allow for bone ingrowth and biological fixation, and eliminate implant loosening and related treatment failures. The unique bone-mimicking properties of porous tantalum enabled the use of tantalum as a material for bulk implants, and not only for coatings, as is the case with other porous metals. Moreover, porous tantalum also facilitates the ingrowth of soft tissue, including the formation of blood vessels that were found to assemble on the surface and within the structure of the porous tantalum. Also, since tantalum is strongly radiopaque due its high atomic number, this property is widely employed for marking in orthopedics and in endovascular medical devices. Another important development was the production of nanoparticles based on tantalum. These particles have been shown to be superior to iodinated contrast agents for blood pool imaging applications due to their longer circulation time. Their properties are similar to gold nanoparticles, but are far more cost-effective, and thus, well-positioned to replace gold in regenerative medicine for labeling and tracking of cell grafts through x-ray-based imaging. However, the amount of tantalum nanoparticles that can be taken up by stem cells is not enough to make individual cells visible in x-ray images. Thus, alternative strategies are needed, such as hydrogel or nanofiber scaffolds, which can be loaded with higher concentrations of nanoparticles, to increase the precision of cell deposition and allow tracking under x-ray guidance.
    Acta neurobiologiae experimentalis 01/2014; 74(2):188-96. · 2.24 Impact Factor
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    • "Therefore, natural polymers including extracellular matrix (ECM) molecules [1], growth factors [2] [3] and glycosaminoglycans [4] [5], have been incorporated into synthetic hydrogels for improved biological activity [6]. Proteins such as collagen and laminin have been physically blended in synthetic hydrogels; however, rapid leaching of proteins from the gels typically occurs over relatively short incubation times [7] [8]. Covalent incorporation of proteins has been achieved via a number of approaches including modification of proteins with synthetic polymers such as poly(ethylene glycol) (PEG), and functionalisation of biological polymers. "
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    ABSTRACT: Development of tissue engineering solutions for biomedical applications has driven the need for integration of biological signals into synthetic materials. Approaches to achieve this typically require chemical modification of the biological molecules. Examples include chemical grafting of synthetic polymers onto protein backbones and covalent modification of proteins using crosslinkable functional groups. However, such chemical modification processes can cause protein degradation, denaturation or loss of biological activity due to side chain disruption. This study exploited the observation that native tyrosine rich proteins could be crosslinked via radical initiated bi-phenol bond formation without any chemical modification of the protein. A new, tyramine functionalised poly(vinyl alcohol) (PVA) polymer was synthesised and characterised. The tyramine modified PVA (PVA-Tyr) was fabricated into hydrogels using a visible light initiated crosslinking system. Mass loss studies showed that PVA-Tyr hydrogels were completely degraded within 19 days most likely via degradation of ester linkages in the network. Protein incorporation to form a biosynthetic hydrogel was achieved using unmodified gelatin, a protein derived from collagen and results showed that 75% of gelatin was retained in the gel post-polymerisation. Incorporation of gelatin did not alter the sol fraction, swelling ratio and degradation profile of the hydrogels, but did significantly improve the cellular interactions. Moreover, incorporation of as little as 0.01 wt% gelatin was sufficient to facilitate fibroblast adhesion onto PVA-Tyr/gelatin hydrogels. Overall, this study details the synthesis of a new functionalised PVA macromer and demonstrates that tyrosine containing proteins can be covalently incorporated into synthetic hydrogels using this innovative PVA-Tyr system. The resultant degradable biosynthetic hydrogels hold great promise as matrices for tissue engineering applications.
    Biomaterials 06/2013; 34(29). DOI:10.1016/j.biomaterials.2013.06.005 · 8.31 Impact Factor
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    • "When surgical repair of the nerve is required, the goal is to guide regenerating sensory, motor, and autonomic axons to the distal nerve segment to maximize the chance of target reinnervation (Pfister et al., 2011). Nerve reconstruction by tissue engineering has seen an increasing interest over the past years (Leach & Schmidt, 2005; Pfister et al., 2011). Despite the "
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    ABSTRACT: After peripheral nerve injuries, the process of nerve regeneration and target reinnervation is very complex and depends on many different events occurring not only at the lesion site but also proximally and distally to it. In spite of the recent scientific and technological advancements, the need to find out new strategies to improve clinical nerve repair and regeneration remains. To reach this goal, the therapeutic strategy should thus exert its effects at different levels in order to simultaneously potentiate axonal regeneration, increase neuronal survival, modulate central reorganization, and inhibit or reduce target organ atrophy. It is expected that this multilevel approach might lead to significant improvement in the functional outcome and thus the quality of life of the patients suffering from peripheral nerve injury.
    International Review of Neurobiology 01/2013; 109C:165-192. DOI:10.1016/B978-0-12-420045-6.00008-0 · 2.46 Impact Factor
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