Tyrosine-derived polycarbonates are currently in preclinical evaluations for biomedical applications. Although physical aging can significantly alter a wide range of polymer properties, physical aging is has rarely been investigated for biomedical polymers. A series of four tyrosinederived polycarbonates was used as a model system to study the effect of polymer structure on the enthalpy relaxation kinetics.

Hylans (hyaluronan derivatives) retain the biological compatibility of the natural hyaluronan and have enhanced rheological properties which expands their utility in medical applications. Hylan materials (hylan A fluid, hylan B gel) were evaluated in a variety of tissue compartments for local and systemic tissue reaction (gross and microscopic), residence time and overall behavior in vivo. Hylan material was implanted into the subcutaneous, intradermal, submucosal, intramuscular, eye (vitreus, anterior chamber, trabecular meshwork), and neural (sciatic nerve) tissues at volumes ranging from 0.50 ml/kg to 20 ml/kg (2.5 mg/kg to 100 mg/kg). There was no difference in tissue response to hylan implants at the various ‘doses’ evaluated; all samples tested were observed to be biocompatible and did not elicit significant tissue response. Therefore, tissue reaction of hylan implants was not dependent on dose or concentration of hylan administered, since implantation of small amounts resulted in the same response as implantation of large amounts of material. In one of the most sensitive tests of biocompatibility, hylan was found to have no adverse effect on nerve regeneration (severed sciatic nerves in rat), and the results indicated that hylan materials “regeneration-friendly” environment for peripheral nerve growth as commatpearriaelds tpor othveid BedS Sa controls.

Hylan materials provide biologically and physically compatible intercellular matrices which are useful in a variety of medical applications, including use as viscosurgical and viscoprotective tools (to maintain space, separate and protect tissues) and as viscosupplementation devices and implants.

The importance of non-enzymatic chemical erosion for the release of drugs from degradable polymers is discussed. In order to have purely erosion controlled systems, polymer erosion has to be faster than polymer swelling or drug diffusivity inside degradable polymers. Therefore, fast hydrolyzing polymers are especially suited for the manufacture of erosion controlled drug delivery systems. Poly(anhydrides) are one such polymer class and are presented in more detail. It is shown that it is possible to predict drug release from such systems using discrete Monte Carlo Models. Such models are useful for the design of new implant type drug delivery systems.

Gamma irradiation is used to sterilize products intended for ophthalmic and parenteral use. Ideally, the sterilization process should not affect the chemical identity or physical properties of the product. We have investigated the effects of gamma irradiation on the structure and molecular weight of hydroxypropyl cellulose (HPC), and the subsequent effect on dissolution behavior of HPC. Hydroxypropyl cellulose is a commonly used excipient in pharmaceutical formulations and tablet coatings, and can be used to manufacture water soluble objects. We find that the moisture content of the HPC influences the extent to which scission and cross-linking reactions occur. At low moisture levels (<5 wt.%), cross-linking is relatively unimportant, while above 12 wt. % moisture cross-linking becomes extensive leading to formation of insoluble, rubber-like gels.

A block copolymer was developed consisting of poly(propylene fumarate) (PPF) and poly(ethylene oxide) (PEO) blocks. The former component allows the copolymer to be crosslinked, while the latter component allows the physical properties to be controlled. The compositions and segmental lengths of the two components were varied, and the copolymer was subsequently characterized.

Ultra High Molecular Weight Polyethylene (UHMWPE) has been and is currently the standard for bearing material used in the orthopedic industry. The components are produced using a variety of manufacturing methods, many of which can have an effect on the longevity and performance of the device. Recently there has been extensive research into the causes of loosening of orthopedic devices. One area that has been targeted as a cause for loosening is reactions to particulate debris from the bearing surfaces of these appliances. As biological reactions to particulate become better understood, there has been an increased emphasis on the quality of the UHMWPE forms used for orthopedic bearing surfaces. Due to this increased awareness, various manufacturing and quality control improvements have been made throughout the industry.

When certain resins are pyrolized they transform into a glassy polymeric carbon (GPC) with no change in shape. Using this process we have made all-carbon heart valves by rapid molding of the component pieces out of precursor resin, assemblage in the resin stage and pyrolysis to at least 1,000°C to form an accurately articulated device. A heart valve with two occluders set in a carbon ring manufactured out of highly polished carbon has been tested with an excellent record of wear, fatigue, resistance and biocompatibility, especially in contact with blood.

A method is described for the preparation β-glycosylamide monomers from reducing carbohydrates. The glycosylamide monomers were copolymerized with acrylamide to formhigh molecular weight, water soluble polymers. The chemical and enzymatic stability of the β-N-glycosidic linkage was investigated. In addition, the glycopolymers were characterized by their interactions with lectins.

Hylan B gel is a viscoelastic insoluble crosslinked derivative of the natural hyaluronan (hyaluronic acid, HA) polymer. Hyaluronan derivatives such as hylan B have enhanced rheological properties and possess the desired biological properties of natural hyaluronan. Hylan B was evaluated in nonclinical in vivo studies for biocompatibility and residence times in dermal tissues. In one study, residence time of radiolabeled [14C]-hylan B was evaluated in guinea pigs following intradermal administration with serial sacrifice (0, 1, 4, 12, 24 weeks). Analysis of radioactivity revealed that at 6 months post-implantation up to 98% of the radioactivity was recovered from the specific injection site (mean 76.7± 29.4%). A half-life time of 12.2 months was estimated from analysis of the data. In another study, the behavior of hylan B gel implanted in the intradermal and subcutaneous tissue of guinea pigs was evaluated at 3 days and at 1, 2, 4, 9, 13, 26 and 52 weeks. In this study, collagen implants were evaluated in parallel with hylan B gel implants in the same animals. Hylan B gel was found to be biologically compatible and stable in the dermal tissue. At one year post-implantation, hylan B gel was detected in a majority (12/16) of test sites. None of the collagen implant materials was detected at one year post-implantation.

Complex coacervation is an appealing method of microencapsulating delicate proteins for controlled drug delivery. Natural polyelectrolytes, such as collagen, gelatin, hyaluronic acid, and chondroitin sulfate, are popular choices for formulating the microspheres. For advantage of versatility, synthetic systems are attractive. Typical synthetic polyelectrolytes are composed of a carbon-carbon backbone that is nonbiodegradable. To design synthetic polyelectrolytes that are biodegradable, we synthesized diamines containing dipeptide or tripeptide sequences that are enzymatically degradable. The enzymatically degradable linkages comprised gly-phe, gly-phe-phe, or gly-gly-phe, and lysine and 2,3-diaminopropionic acid co-monomers served as the charged component. Using an interfacial polymerization technique, these monomers were condensed with diacyl chlorides, including succinyl, adipoyl, or terephthaloyl chloride to form polyamides. Results of gel permeation chromatography and ninhydrin assays showed that the polymers degraded in PBS containing α-chymotrypsin.