Tyrosine-derived polycarbonates

Pulapura, S. and Kohn, J. Tyrosine Derived Polycarbonates New Polymers for Medical Applications, manuscript in preparation. 

Particularly noteworthy are the tyrosine-derived polycarbonates (27), a family of polymers based on alkyl esters of desaminotyrosyl-tyrosine. The lead polymer in this family is poly[desaminotyrosyl-tyrosine ethyl ester (DTE) carbonate], a polymer derived from desaminotyrosyl-tyrosine ethyl ester. Other polymers in this series of tyrosine-derived polycarbonates are poly[desaminotyrosyl-tyrosine butyl ester (DTB) carbonate], poly[desaminotyrosyl-tyrosine hexyl ester (DTH) carbonate], and poly [desaminotyrosyl-tyrosine octyl ester (DTO) carbonate], where the letters B, H, and O indicate the presence of butyl, hexyl, or octyl ester pendent chains, respectively. 

Ertel SI, Kohn J. Evaluation of a series of tyrosine-derived polycarbonates as degradable biomaterials. J Biomed Mater Res 1994 28 919-930. 

M.H.C. Resurreccion-Magno, Optimization of tyrosine-derived polycarbonate terpolymers for bone regeneration scaffolds. Dissertation, Rutgers University, New Brunswick, NJ, 2012. 

A.J. Asikainen, J. Noponen, C. Undqvist, M. Pelto, M. Kellomaki, H. Juuti, H. Pihlajamaki, R. Suuronen, Tyrosine-derived polycarbonate membrane in treating mandibular bone defects. An experimental smdy, J. R. Soc. Interface 3 (2006) 629-635. 

Z. Dong, Synthesis of Four Structurally Related Tyrosine-Derived Polycarbonates and In Vitro Study of Dopamine Release from Poly(Desaminotyrosyl-Tyrosine Hexyl Ester Carbonate), Master s Thesis, Rutgers University, New Bnmswick, NJ, 1993. 

Another example of a biodegradable stent is the REVA (Reva Medical Inc., San Diego, CA), a tyrosine-derived polycarbonate, which after metabolism produces amino acids, ethanol, and carbon dioxide. The REVA is balloon expandable with a slide and lock design which allows the expansion of the stent without deformation (Figure 5C). Iodine is its source of radiopacity. It has thick struts of 200 microns. Preclinical data show complete re-endothelialization [81]. Currently, the paclitaxel-eluting REVA stent is under development. 

Poly(amino acids), poly(anhydrides), poly(caprolactones), poly(lactic/glycolic) acid cr lymers, poly(hydroxybutyrates), poly(orthoesters), tyrosine-derived polycarbonates... 

Ertel, S.I., and J. Kohn. 1994. Evaluation of a sraies of tyrosine-derived polycarbonates as degratlable biomaterials. Journal of Biomedical Materials Research 28(8) 919-930. 

Tangpasuthadol, V., et al. 2000. Hydrol3dic degradation of tyrosine-derived polycarbonates, a class of new biomaterials. Part II 3-yr study of polymeric devices. Biomaterials 21(23) 2379-2387. 

Kim, J., et al. 2012. Bone regeneration in a rabbit critical-sized calvarial model using tyrosine-derived polycarbonate scaffolds. Tissue Engineering Part A 18(11-12) 1132-1139. 

Magno, M.H.R., et al. 2010. Synthesis, degradation and biocompatibility of tyrosine-derived polycarbonate scaffolds. Journal of Materials Chemistry 20(40) 8885-8893. 

Ezra, M., et al. 2013. Enhanced femoral nerve regeneration after tubulization with a tyrosine-derived polycarbonate terpolymer effects of protein adsorption and independence of conduit porosity. Tissue Engineering Part A 20(3 ) 518-528. 

Johnson, P.A., et al. 2010. Interplay of anionic charge, poly (ethylene glycol), and iodinated tyrosine incorporation within tyrosine-derived polycarbonates Effects on vascular smooth muscle cell adhesion, proliferation, and motility. Journal of Biomedical Materials Research, Part A 93(2) 505-514. 

Pulapura, S., and J. Kohn. 1992. Tyrosine-derived polycarbonates backbone-modified pseudo -poly(amino acids) designed for biomedical appUcations. Biopolymers 32(4) 411-417. 

Perez-Luna, V.H., Hooper, K.A., Kohn, X, Ratner, B.D. (1997) Surface characterization of tyrosine-derived polycarbonates. J. Appl. Polym. ScL, 63,1467-1479. 

Pseudo-poly(amino acids) were first described in 1984 (Kohn, 1984) and have since been evaluated for use in several medical applications (Kohn, 1987 Yu-Kwon, 1989 Zhou, 1990 Kohn, 1993 Mao, 1993). Although a range of different pseudo-poly(amino acids) has been prepared, detailed studies of the physical properties, biological properties, and possible applications of these polymers have so far been conducted only for a select group of new tyrosine- derived polycarbonates, polyiminocarbonates, and polyarylates. This review will encompass the work to date on these specific materials. 

Table 1 Some Physical Properties of Tyrosine-Derived Polycarbonates ... 

Rgure 3 Reaction scheme for the preparation of tyrosine-derived polycarbonates. The monomers are polymerized by reaction with phosgene. 

Tyrosine-derived polycarbonates have important advantages when used in the design of implantable, degradable controlled release systems. First, all members of this series of polymers are amorphous materials with relatively low glass transition temperatures which are a function of the pendent chain length (Tdhte 1). X-ray diffraction... 

Tyrosine-derived polycarbonates provided a convenient model system to study the effect of pendent chain length on the thermal properties and the enthalpy relaxation (physical aging). It is noteworthy that enthalpy relaxation kinetics are not usually reported in the biomedical literature and that a recent study by Tangpasuthadol (Tangpasuthadol, 1995) represents one of the first attempts to evaluate physical aging in a degradable biomedical polymer. 

For the tyrosine-derived polycarbonates tested, the enthalpy relaxation process was not sensitive to the length of the pendent chain. This obser ation suggests that structural relaxation in these polymers is limited by backbone flexibility, and that the fraction of free volume in these polymers is not the limiting factor for polymer mobility. Furthermore, since the enthalpy relaxation time is short at aging temperatures of Tg-15°C, a few hours of storage at that temperature will be sufficient to bring the physical aging process to completion. The results obtained by dynamic... 

In vitro attachment and proliferation of fibroblasts on tyrosine-derived polycarbonates w as a function of the pendent chain length (Ertel, 1994). Consistent with the hypothesis that cells favor more hydrophilic and molecularly rigid surfaces, poly(DTE carbonate), the most hydrophilic and rigid of the surfaces tested (TaWte I), supported cell growth and proliferation better than the more hydrophobic poly(DTO carbonate). Poly(DTB carbonate) and poly(DTH carbonate) were intermediate in their ability to support ceU attachment and growth. 

The presence of a fibrous layer surrounding the PLA coupons is characteristic of a mild foreign body response. That such a fibrous layer was not formed at the bone/material interface for poly(DTE carbonate) and poly(DTH carbonate) is an important characteristic of these polymers. Intimate contact between bone and implant, even at 48 weeks post-implantation, is a strong indicator of the biocompatibility of the tyrosine-derived polycarbonates. 

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