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: 8.56). 01/2005; 26(2):125-35. DOI: 10.1016/j.biomaterials.2004.02.018
Source: PubMed


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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    • "Due to the nonspecific reactions of free radicals and the large number of free amines available in growth factors, free radical and aldehyde reaction strategies, respectively, are unsuitable for growth factor delivery due to potential denaturation of the growth factor, unless the growth factor is protected in some fashion. This protection could be afforded through incorporation into a hydrophobic polymer microsphere [25] [26], solid lipid particle [27], or through distribution of the protein as a poorly soluble salt particle [28]. Furthermore, despite the high yield, specific reaction afforded by Diels–Alder reactions, which occur under mild aqueous conditions, gelation times are inordinately long [29]. "
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    ABSTRACT: Growth factors represent an important therapeutic protein drug class, and would benefit significantly from formulations that provide sustained, local release to realize their full clinical potential. Biodegradable polymer-based delivery platforms have been examined to achieve this end; however, formulations based on conventional polymers have yet to yield a clinical product. This review examines new polymer biomaterials that have been developed for growth factor delivery. The dosage forms are discussed in terms of their mechanism of release, the stability of the released growth factor, their method of preparation, and their potential for clinical translation.
    Full-text · Article · Nov 2015 · European Journal of Pharmaceutics and Biopharmaceutics
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    • "Several HA derivatives have been developed for drug delivery [10], mainly for its potential as a biodegradable carrier [11]. Some authors have reported the use of this polymer for different proteins, drugs [12], peptides [13] or for gene delivery [14] [15] using HA as a depot system [16], as hydrogels (physically and chemically cross-linked) [17] [18] [19] or as nano-or micro-particulate systems [20] [21]. Studies related to biocompatibility and biodegradability [22] have supported the use of HA as a promising biomaterial to design modified drug delivery systems. "
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    ABSTRACT: New hyaluronic acid–itaconic acid films were synthesized as potential materials with biomedical applications. In this work, we explored the homogeneous cross-linking reactions of hyaluronic acid using glutaraldehyde in the presence of itaconic acid and triacetin as plasticizers. Biomechanical properties were assessed in terms of stability by measuring swelling in aqueous environments, investigating wettability using contact angle tests and evaluating bioadhesive performance. The ductility of the materials was evaluated through stress-strain measurements and the morphology was explored by scanning electron microscopy. The results show that the incorporation of itaconic acid improved most of the desirable properties, increasing adhesiveness and reducing wettability and swelling. The use of triacetin enhanced the strength, bioadhesiveness and ductility of the material.
    Full-text · Article · Jan 2015 · Scientia Pharmaceutica
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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.
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