Joost P. Bruggeman

Biocompatibility of biodegradable semiconducting melanin films for nerve tissue engineering

The advancement of tissue engineering is contingent upon the development and implementation of advanced biomaterials. Conductive polymers have demonstrated potential for use as a medium for electrical stimulation, which has shown to be beneficial in many regenerative medicine strategies including neural and cardiac tissue engineering. Melanins are naturally occurring pigments that have previously been shown to exhibit unique electrical properties. This study evaluates the potential use of melanin films as a semiconducting material for tissue engineering applications. Melanin thin films were produced by solution processing and the physical properties were characterized. Films were molecularly smooth with a roughness (R(ms)) of 0.341 nm and a conductivity of 7.00+/-1.10 x 10(-5)S cm(-1) in the hydrated state. In vitro biocompatibility was evaluated by Schwann cell attachment and growth as well as neurite extension in PC12 cells. In vivo histology was evaluated by examining the biomaterial-tissue response of melanin implants placed in close proximity to peripheral nerve tissue. Melanin thin films enhanced Schwann cell growth and neurite extension compared to collagen films in vitro. Melanin films induced an inflammation response that was comparable to silicone implants in vivo. Furthermore, melanin implants were significantly resorbed after 8 weeks. These results suggest that solution-processed melanin thin films have the potential for use as a biodegradable semiconducting biomaterial for use in tissue engineering applications.

Biodegradable poly(polyol sebacate) polymers

We have developed a family of synthetic biodegradable polymers that are composed of structural units endogenous to the human metabolism, designated poly(polyol sebacate) (PPS) polymers. Material properties of PPS polymers can be tuned by altering the polyol monomer and reacting stiochiometric ratio of sebacic acid. These thermoset networks exhibited tensile Youngs moduli ranging from 0.37+/-0.08 to 378+/-33 MPa with maximum elongations at break from 10.90+/-1.37% to 205.16+/-55.76%, and glass transition temperatures ranging from approximately 7-46 degrees C. In vitro degradation under physiological conditions was slower than in vivo degradation rates observed for some PPS polymers. PPS polymers demonstrated similar in vitro and in vivo biocompatibility compared to poly(L-lactic-co-glycolic acid) (PLGA).

Amino alcohol-based degradable poly(ester amide) elastomers

Currently available synthetic biodegradable elastomers are primarily composed of crosslinked aliphatic polyesters, which suffer from deficiencies including (1) high crosslink densities, which results in exceedingly high stiffness, (2) rapid degradation upon implantation, or (3) limited chemical moieties for chemical modification. Herein, we have developed poly(1,3-diamino-2-hydroxypropane-co-polyol sebacate)s, a new class of synthetic, biodegradable elastomeric poly(ester amide)s composed of crosslinked networks based on an amino alcohol. These crosslinked networks feature tensile Youngs modulus on the order of 1MPa and reversable elongations up to 92%. These polymers exhibit in vitro and in vivo biocompatibility. These polymers have projected degradation half-lives up to 20 months in vivo.

Biodegradable xylitol-based elastomers: In vivo behavior and biocompatibility

Biodegradable elastomers based on polycondensation reactions of xylitol with sebacic acid, referred to as poly(xylitol sebacate) (PXS) elastomers have recently been developed. We describe the in vivo behavior of PXS elastomers. Four PXS elastomers were synthesized, characterized, and compared with poly(L-lactic-co-glycolic acid) (PLGA). PXS elastomers displayed a high level of structural integrity and form stability during degradation. The in vivo half-life ranged from approximately 3 to 52 weeks. PXS elastomers exhibited increased biocompatibility compared with PLGA implants.

In vitro and in vivo degradation of poly(1,3-diamino-2-hydroxypropane-co- polyol sebacate) elastomers

Biomaterials with a wide range of tunable properties are desirable for application-specific purposes. We have previously developed a class of elastomeric poly(ester amides) based on the amine alcohol 1,3-diamino-2-hydroxypropane termed poly(1,3-diamino-2-hydroxypropane-co-polyol sebacate) or APS. In this work, we have synthesized and characterized formulations of APS polymers and studied the degradation of these polymers in vitro and in vivo. It was found that the chemical, physical, and mechanical properties of APS polymers could be tuned by adjusting monomer feed ratios and polymerization conditions. The degradation kinetics could also be greatly influenced by altering the formulation of APS polymers. In vivo degradation half-lives ranged from 6 to approximately 100 weeks. Furthermore, the dominant degradation mechanism (i.e. hydrolytic or enzymatic) could be controlled by adjusting the specific formulation of the APS polymer. On the basis of the observed in vitro and in vivo biodegradation phenomena, we also propose that the primary modes of degradation are composition dependent.

Prevention of peritoneal adhesions using polymeric rheological blends

The effectiveness of rheological blends of high molecular weight hyaluronic acid (HA) and low molecular weight hydroxypropyl methylcellulose (HPMC) in the prevention of peritoneal adhesions post-surgery is demonstrated. The physical mixture of the two carbohydrates increased the dwell time in the peritoneum while significantly improving the injectability of the polymer compared with HA alone. HA-HPMC treatment decreased the total adhesion area by ∼ 70% relative to a saline control or no treatment in a repeated cecal injury model in the rabbit. No significant cytotoxicity and minimal inflammation were associated with the blend. Furthermore, no chemical or physical processing was required prior to their use beyond simple mixing.