Showing papers by "Jason A. Burdick published in 2006"
TL;DR: This work has developed a method for attaching molecules to the surface of PPy through biotin–streptavidin coupling, which provides a novel platform for controlled drug delivery from a conductive polymer substrate.
Abstract: An externally controlled, polymeric drug-delivery system potentially allows for release profiles that can be tailored to match physiologic processes. [1] Current implantable electronic delivery systems are not biodegradable and often require additional components, while extended- or controllable-release polymeric systems that have been used do not allow for switchable release profiles. [2,3] Conducting polymers (e.g., polypyrrole (PPy)) offer the possibility of controllable drug administration through electrical stimulation. [4] However, the use of conductive polymers in delivery systems has been restricted due to limitations in the choice of dopant and the molecular weight of the delivered drug. To circumvent these barriers, we have developed a method for attaching molecules to the surface of PPy through biotin–streptavidin coupling. After attachment of the desired molecule to the biotin dopant, drug release is triggered through electrical stimulation. This method provides a novel platform for controlled drug delivery from a conductive polymer substrate. Because of PPy’s beneficial chemical properties and ease of preparation, it is often chosen for biological applications. [5–7] PPy’s favorable biocompatibility also makes it an ideal electroactive polymer for drug-delivery applications. [8–13] Addi
298 citations
TL;DR: Hydrogels based on poly(ethylene glycol) that form via a photoinitiated polymerization were investigated for the delivery of neurotrophic factors and unique microsphere/hydrogel composites were developed to simultaneously deliver multiple neurotrophins with individual release rates.
243 citations
TL;DR: It is demonstrated that it is possible to incorporate photocrosslinkable HA, a natural, versatile, degradable, and biocompatible biopolymer, into micro-electromechanical systems.
Abstract: Micropatterning of hydrogels is potentially useful for a variety of applications, including tissue engineering, fundamental biological studies, diagnostics, and high-throughput screening. Although synthetic polymers have been developed for these applications, natural polymers such as polysaccharides may have advantages for biological samples and cell-based devices because they are natural components of the in vivo microenvironment. In this study, we synthesized and used hyaluronic acid (HA) modified with photoreactive methacrylates to fabricate microstructures as functional components of microfabricated devices. To demonstrate the universality of this approach, two types of microstructures were formed. In the first approach, HA microstructures were fabricated and used as docking templates to enable the subsequent formation of cell microarrays within low shear stress regions of the patterns. Cells within these microwells remained viable, could generate spheroids, and could be retrieved using mechanical disruption. In the second approach, cells were encapsulated directly within the HA hydrogels. Arrays of viable embryonic stem (ES) cells or fibroblasts were encapsulated within HA hydrogels and could later be recovered using enzymatic digestion of the microstructures. These results demonstrate that it is possible to incorporate photocrosslinkable HA, a natural, versatile, degradable, and biocompatible biopolymer, into micro-electromechanical systems.
232 citations
TL;DR: Hydrogel release properties were established in vitro to ensure long-term, sustained NT-3 release over a 2-week period; this avoided the need for multiple injections or minipump implantation.
194 citations
TL;DR: This work develops the first combinatorial library of degradable photocrosslinked materials, a library of Krylate-terminated polymers with diverse properties such as cadmium, cadmiferous material, and polymethine.
Abstract: However, the synthesis of multifunctional macro-mers that form these degradable networks commonly involvesmultiple functionalization and purification steps, which makesthe development of large numbers of polymers with diverseproperties difficult. Here, we develop the first combinatoriallibrary of degradable photocrosslinked materials. A library ofacrylate-terminated poly(
163 citations
TL;DR: Hydrogels fabricated from 2 wt % of the 50 kDa HA macromer most resembled the properties of native cartilage and show the greatest promise for continued development for cartilage regeneration.
Abstract: The objective of this study was to determine how changes in the network structure and properties of hyaluronic acid (HA) hydrogels, due to variations in the macromer molecular weight (50-1,100 kDa) and macromer concentration (2-20 wt %), affect neocartilage formation by encapsulated auricular chondrocytes To investigate tissue formation, swine auricular chondrocytes were photoencapsulated in the various networks, implanted subcutaneously in the dorsum of nude mice, and explanted after 6 and 12 weeks for biochemical and histological analysis After 12 weeks, the various constructs were 81-93% water, contained between 01 x 10(6) and 06 x 10(6) chondrocytes per sample, and consisted of 0-0049 microg chondroitin sulfate/mug wet weight (glycosaminoglycan (GAG) content) and 0002-0060 microg collagen/microg wet weight Histological staining showed an even distribution of chondrocytes and GAGs in addition to minimal type I collagen staining and intense and uniform type II collagen staining in the constructs with greatest neocartilage production Hydrogels fabricated from 2 wt % of the 50 kDa HA macromer most resembled the properties of native cartilage and show the greatest promise for continued development for cartilage regeneration
146 citations
TL;DR: Overall, this study illustrates that constructs with the p = 0 and p = 1 auricular chondrocytes produced neocartilage tissue that resembled native auricular cartilage after 12 weeks in vivo, however, these results indicate that further expansion of the chondROcytes can lead to compromised tissue properties.
Abstract: The overall objective of this study was to examine the effects of in vitro expansion on neocartilage formation by auricular chondrocytes photoencapsulated in a hyaluronic acid (HA) hydrogel as a next step towards the clinical application of tissue engineering therapies for treatment of damaged cartilage. Swine auricular chondrocytes were encapsulated either directly after isolation (p = 0), or after further in vitro expansion (p = 1 and p = 2) in a 2 wt%, 50 kDa HA hydrogel and implanted subcutaneously in the dorsum of nude mice. After 12 weeks, constructs were explanted for mechanical testing and biochemical and immunohistochemical analysis and compared to controls of HA gels alone and native cartilage. The compressive equilibrium moduli of the p = 0 and p = 1 constructs (51.2 ± 8.0 and 72.5 ± 35.2 kPa, respectively) were greater than the p = 2 constructs (26.8 ± 14.9 kPa) and the control HA gel alone (12.3 ± 1.3 kPa) and comparable to auricular cartilage (35.1 ± 12.2 kPa). Biochemical analysis showed a general decrease in glycosaminoglycan (GAG), collagen, and elastin content with chondrocyte passage, though no significant differences were found between the p = 0 and p = 1 constructs for any of the analyses. Histological staining showed intense and uniform staining for aggrecan, as well as greater type II collagen versus type I collagen staining in all constructs. Overall, this study illustrates that constructs with the p = 0 and p = 1 auricular chondrocytes produced neocartilage tissue that resembled native auricular cartilage after 12 weeks in vivo. However, these results indicate that further expansion of the chondrocytes (p = 2) can lead to compromised tissue properties.
112 citations
TL;DR: The view that the predictive value of in vitro cytotoxicity assays in matters of biocompatibility may not be sufficient is reinforced, and other assays such as cytokine levels may be of value in predicting outcomes in situations involving multiple cell types (i.e. in vivo).
Abstract: The suitability of chitosan and UV-cross-linkable chitosan for intraperitoneal use, for example as a barrier device for preventing peritoneal adhesions or for drug delivery, was examined. In vitro experiments using two major cell types present in the peritoneal cavity (mesothelial cells and peritoneal macrophages) revealed neither attractive interactions between cross-linked chitosan gels and the cells nor a proliferative effect. However, the same UV-cross-linked chitosan applied in the peritoneal cavity of rabbits caused a granulomatous reaction with adhesion formation within two weeks in all animals, which persisted up to 4 weeks after exposure. Unmodified chitosan also caused adhesions, while UV irradiation did not. UV-cross-linkable chitosan induced significant elevations in MIP-2 and TNF-alpha from peritoneal macrophages, suggesting that soluble mediators could play a role in inducing adhesion formation. These results reinforce the view that the predictive value of in vitro cytotoxicity assays in matters of biocompatibility may not be sufficient, and suggest that other assays such as cytokine levels may be of value in predicting outcomes in situations involving multiple cell types (i.e. in vivo).
68 citations
Patent•
22 Jun 200615 citations
TL;DR: The first combinatorial library of degradable photocrosslinked materials was reported on p.2614 by Anderson, Burdick, and co-workers as discussed by the authors, which showed a three-dimensional representation of the generic macromer, superimposed onto a microarray of materials.
Abstract: The first combinatorial library of degradable photocrosslinked materials is reported on p. 2614 by Anderson, Burdick, and co-workers. The inside cover shows a three-dimensional representation of the generic macromer, superimposed onto a microarray of materials. It is believed that this library approach will allow for the rapid screening and design of degradable polymers for a variety of applications.
2 citations