Synthesis and physicochemical analysis of interpenetrating networks containing modified gelatin and poly(ethylene glycol) diacrylate

The interrelated effects of gelatin modification, content, and poly(ethylene glycol) molecular weight on the melting temperature, surface hydrophilicity, tensile properties, swelling/degradation, and drug-release kinetics of a novel interpenetrating network (IPN) system containing gelatin and poly(ethylene glycol) diacrylate were evaluated. Gelatin content had a large effect on the IPN melting temperature and ΔH. Modifying gelatin with ethylenediaminetetraacetic acid and/or monomethoxy poly(ethylene glycol) monoacetate ester as well as increasing poly(ethylene glycol) diacrylate molecular weight increased the surface hydrophilicity. Increasing the gelatin weight percent increased the IPN elasticity at room temperature. When buffer and elevated temperature were present in the testing environment, the elasticity of all IPNs tested decreased. IPNs showed an enhanced elasticity and strength when compared with glutaraldehyde-fixed gelatin hydrogels. The extent of IPN swelling and degradation was increased by increasing the gelatin content or by modifying gelatin. The time to complete sample degradation was longer for IPNs when compared with gelatin crosslinked with glutaraldehyde. Modifications to the IPN system increased the maximum percent of chlorhexidine digluconate released from the IPNs. The rate of complete drug release was slower from IPNs than from glutaraldehyde-fixed gelatin matrices. A wide range of IPN physicochemical properties was obtained through formulation changes and chemical modifications. © 2003 Wiley Periodicals, Inc.Link_to_subscribed_fulltex

In vivo biocompatibility of gelatin-based hydrogels and interpenetrating networks

The in vivo host response to two gelatin-based hydrogel systems of varying crosslinking modalities and loaded with the anti-inflammatory agent dexamethasone sodium phosphate was investigated. Either gelatin was chemically crosslinked with glutaraldehyde, or polyethyleneglycol diacrylate was photopolymerized around gelatin to form interpenetrating networks. The subcutaneous cage implant system was utilized to determine differential leukocyte concentrations in the inflammatory exudate surrounding the materials as indices for biocompatibility and drug efficacy in vivo. Most of the crosslinked gelatin-based materials, either via glutaraldehyde fixation or interpenetrating network formation, elicited stronger inflammatory responses than either of the starting materials, gelatin and polyethyleneglycol diacrylate. In general, dexamethasone delayed and intensified the inflammatory response. The loss of material mass did not correlate directly with the degree of cellular inflammatory response, but increased with longer implantation time and decreased with more extensive fixation.Link_to_subscribed_fulltex

A study of diffusion in poly(ethyleneglycol)-gelatin based semi-interpenetrating networks for use in wound healing

Semi-interpenetrating networks (sIPNs) designed to mimic extracellular matrix via covalent crosslinking of poly(ethylene glycol) diacrylate in the presence of gelatin have been shown to aid in wound healing, particularly when loaded with soluble factors. Ideal systems for tissue repair permit an effective release of therapeutic agents and flow of nutrients to proliferating cells. Appropriate network characterization can, consequently, be used to convey an understanding of the mass transfer kinetics necessary for materials to aid in the wound healing process. Solute transport from and through sIPNs has not yet been thoroughly evaluated. In the current study, the diffusivity of growth factors and nutrients through the polymeric system was determined. Transport of keratinocyte growth factor was modeled by treating the sIPN as a plane sheet into which the protein was loaded. The diffusion coefficient was determined to be 4.86 × 10(−9) ± 1.86 × 10(−12) cm(2)/s. Glucose transport was modeled as flow through a semi-permeable membrane. Using lag-time analysis, the diffusion coefficient was calculated to be 2.25 × 10(−6) ± 1.98 × 10(−7) cm(2)/s. The results were evaluated in conjunction with previous studies on controlled drug release from sIPNs. As expected from Einstein-Stokes equation, diffusivity decreased as molecular size increased. The results offer insight into the structure-function design paradigm and show that release from the polymeric system is diffusion controlled, rather than dissolution controlled

Modulation of the keratinocyte-fibroblast paracrine relationship with gelatin-based semi-interpenetrating networks containing bioactive factors for wound repair

Gelatin-based semi-interpenetrating networks (sIPNs) containing soluble and covalently-linked bioactive factors have been shown to aid in wound healing; however, the biological responses elicited by the introduction of sIPN biomaterials remain unclear. In the current study, modulation of the re-epithelialization phase of wound healing by sIPNs grafted with PEGylated fibronectin-derived peptides and utilized as platforms for the delivery of exogenous keratinocyte growth factor (KGF) was evaluated. Following wounding, keratinocyte migration, proliferation and protein secretion is largely controlled by diffusible factors, such as KGF, released by the underlying fibroblasts. The impact of sIPNs and exogenous KGF upon the latter keratinocyte-fibroblast paracrine relationship and keratinocyte behavior was explored by monitoring keratinocyte adhesion and cytokine (IL-1α, IL-1β, IL-6, KGF, GM-CSF and TGF-α) release. Results were generally similar for keratinocyte monoculture and keratinocyte-fibroblast co-culture systems. Although keratinocyte adhesion increased over time for positive control surfaces, adhesion to the sIPNs remained low throughout the course of the study. Release of IL-1α and GM-CSF was increased by exogenous KGF. The effects were more noticeable on the positive control surfaces relative to the sIPN surfaces. Regulation of the release of TGF-α was surface dependent, while IL-6 release was dependent upon surface type, the inclusion of exogenous KGF and the presence of fibroblasts. The findings indicate that during re-epithelialization, sIPNs containing soluble bioactive factors aid in wound healing primarily by serving as conduits for KGF, which induces the release of other key cytokines involved in tissue repair. © 2009 Koninklijke Brill NV, Leiden.Link_to_subscribed_fulltex