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Applications of Polymers in Bioseparations and Delivery of Biomolecules
Hoffman, Allan S. The Korean Society of Medical and Biological Engin 1986 의공학회지 Vol.7 No.2
Polymers are widely applied in bioseparation processes as well as in drug delivery systems. These two fields have a certain commonality, in that they involve either removal or delivery of specific biomolecules from or to an aqueous environment It is also to be noted that therapeutic toxin renloval is an example of a bioseparation process. This presentation will focus on the use of polys!ors in physical as well as biospecific separations and delivery of biomolecules. Several new systems will also be described.
Heparin-regulated delivery of osteoprotegerin promotes vascularization of implanted hydrogels
McGonigle, Joseph S.,Tae, Giyoong,Stayton, Patrick S.,Hoffman, Allan S.,Scatena, Marta Informa UK (TaylorFrancis) 2008 Journal of biomaterials science, Polymer edition Vol.19 No.8
<P>Localized, controlled delivery of pro-angiogenic agents is an important component of therapies for chronic wound treatment and regenerative medicine. Osteoprotegerin (OPG), a tumor necrosis factor receptor (TNFR) superfamily member has recently been shown to be pro-angiogenic in vitro, and we hypothesized that controlled delivery of OPG could induce angiogenesis in vivo. OPG contains a highly basic heparin-binding domain, suggesting that affinity interactions could be used to control the rate of its ion-exchange-driven release from drug-delivery devices. Here, we describe the use of a hydrogel consisting of thiol-modified heparin which can be readily and controllably cross-linked using a bi-functional PEG-diacrylate. These hydrogels were found to retain between 750 and 900 ng of immunoreactive OPG for up to 500 h in in vitro release studies. OPG containing hydrogels were evaluated in a subcutaneous mouse implant model, and exhibited little degradation and retained OPG as indicated by immunohistochemistry at 2 weeks post-implantation. Immunohistochemical analysis of implanted gels indicated that OPG induced nearly a 2-fold increase in vascular density in the surrounding foreign body capsule. These results suggest that the controlled delivery of OPG can stimulate angiogenesis in vivo and may be of use for wound healing therapies as well as other inflammatory and bone disorders in which OPG plays a role.</P>
Sei Kwang Hahn,Allan S. Hoffman 한국생물공학회 2004 Biotechnology and Bioprocess Engineering Vol.9 No.3
A biocompatible polyelectrolyte complex multilayer (PECML) film consisting of poly-L-lysine (PLL) as a polycation and hyaluronic acid (HA) as a polyanion was developed to test its use for surface modification to prevent cell attachment and protein drug delivery. The formation of PECML through the electrostatic interaction of HA and PLL was confirmed by contact angle measurement, ESCA analysis, and HA content analysis. HA content increased rapidly up to 8 cycles for HA/PLL deposition and then slightly increased with an increasing number of deposition cycle. In vitro release of PLL in the PECML continued up to 4 days and ca. 25% of HA remained on the chitosan-coated cover glass after in vitro release test for 7 days. From the results, PECML of HA and PLL appeared to be stable for about 4 days. The surface modification of the chitosan-coated cover glass with PECML resulted in drastically reduced peripheral blood mononuclear cell (PBMC) attachment. Concerned with its use for protein drug delivery, we confirmed that bovine serum albumin (BSA) as a model protein could be incorporated into the PECML and its release might be triggered by the degradation of HA with hyaluronidase.
Tae, Giyoong,Scatena, Marta,Stayton, Patrick S.,Hoffman, Allan S. Informa UK (TaylorFrancis) 2006 Journal of biomaterials science, Polymer edition Vol.17 No.1
<P>An affinity-based controlled release system for growth factors having heparin-binding domains was prepared using a cross-linked heparin gel. The heparin gel was made by reacting hydrazide-functionalized heparin (Hep-ADH) with the N-hydroxysuccinimidyl ester of poly(ethylene glycol)-bis-butanoic acid (SBA-PEG-SBA). The degree of cross-linking could be controlled by defining the stoichiometry of hydrazide modification and the PEG cross-linker addition. The release of vascular endothelial growth factor (VEGF) was characterized as a heparin-binding growth factor. VEGF was directly injected into the heparin gel and the loaded VEGF displayed a slow, controlled release over 3 weeks with little initial burst phase. The biological activity of the released VEGF was measured with a proliferation assay utilizing human umbilical vein endothelial cells. The released VEGF maintained its biological activity at all time points investigated. The heparin gel with loaded VEGF was implanted sub-cutaneously in the dorsal region of mice. A significantly increased density of the endothelial cell marker platelet endothelial adhesion molecule (PECAM-1) was observed in histological specimens of the tissues surrounding the implanted gel.</P>
Park, Kyeng Min,Yang, Jeong-A,Jung, Hyuntae,Yeom, Junseok,Park, Ji Sun,Park, Keun-Hong,Hoffman, Allan S.,Hahn, Sei Kwang,Kim, Kimoon American Chemical Society 2012 ACS NANO Vol.6 No.4
<P>A facile <I>in situ</I> supramolecular assembly and modular modification of biocompatible hydrogels were demonstrated using cucurbit[6]uril-conjugated hyaluronic acid (CB[6]-HA), diaminohexane-conjugated HA (DAH-HA), and tags-CB[6] for cellular engineering applications. The strong and selective host–guest interaction between CB[6] and DAH made possible the supramolecular assembly of CB[6]/DAH-HA hydrogels in the presence of cells. Then, the 3D environment of CB[6]/DAH-HA hydrogels was modularly modified by the simple treatment with various multifunctional tags-CB[6]. Furthermore, we could confirm <I>in situ</I> formation of CB[6]/DAH-HA hydrogels under the skin of nude mice by sequential subcutaneous injections of CB[6]-HA and DAH-HA solutions. The fluorescence of modularly modified fluorescein isothiocyanate (FITC)-CB[6] in the hydrogels was maintained for up to 11 days, reflecting the feasibility to deliver the proper cues for cellular proliferation and differentiation in the body. Taken together, CB[6]/DAH-HA hydrogels might be successfully exploited as a 3D artificial extracellular matrix for various tissue engineering applications.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/ancac3/2012/ancac3.2012.6.issue-4/nn204123p/production/images/medium/nn-2011-04123p_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/nn204123p'>ACS Electronic Supporting Info</A></P>