Cornelis A. P. Joziasse

HIGH-IMPACT POLY(L/D-LACTIDE) FOR FRACTURE FIXATION - IN-VITRO DEGRADATION AND ANIMAL PILOT-STUDY

The impact strength of amorphous lactide copolymers can be significantly improved by blending with biodegradable rubbers. Rubber toughening of amorphous poly(85L/15D -lactide) with the copolymer poly (50/50-trimethylenecarbonate-co-epsilon-caprolactone) results in a high-impact polymer (PDLLA/P(TMC-CL)). In vitro, the PDLLA/P(TMC-CL) blend retained its tensile and impact strength for a long period of time. Up to 45 weeks, the amount of water absorbed by the blend remained very low and no significant mass loss was observed. To test the suitability for fracture fixation, in a dog study mandibular fractures were fixated with PDLLA/P(TMC-CL) bone plates and screws. Bone healing was uneventful without premature failure of the implants. Although long-term degradation studies have to be carried out, PDLLA/P(TMC-CL) seems to be promising for application in fracture fixation.

Cytotoxicity of poly(96L/4D-lactide): the influence of degradation and sterilization.

The cytotoxicity of poly(96L/4D-lactide) (PLA96), and of its accumulated degradation products, was investigated following different sterilization methods and pre-determined heat-accelerated degradation intervals. PLA96 samples sterilized by either steam, ethylene oxide, or gamma irradiation were left untreated (S0 samples), or were degraded for 30 h or 60 h (S30 and S60 samples) at 90 degrees C in water. Extracts of the samples and of the remaining degradation fluids (F30 and F60) were prepared. The toxicity of both unfiltered and filtered extracts was analyzed in a cell growth inhibition (CGI) assay and a lactate dehydrogenase (LDH) leakage assay. Physical analysis of the extracted samples and of the degradation fluids also was performed. The S0 extracts demonstrated no significant CGI. The CGI of the S30 extracts ranged from 37 to 78%, whereas the CGI of the S60 extracts ranged from 6 to 33%. The CGI of the F30 extracts ranged from 19 to 38% and the CGI of the F60 extracts was 98 to 123%. The LDH leakage assay only showed a high response to the unfiltered F60 extracts. Neither sterilization nor filtration appeared to influence the cytotoxicity of the extracts. Particle accumulation, however, might affect cell membrane permeability resulting in LDH leakage. The results of this study suggest that the cytotoxicity of PLA96 is related to the pH and possibly the osmolarity of the tested extracts. The pH and osmolarity, in turn, may depend on variations in the amounts of solubilized lactic acid and oligomers. These variations appear to result from degradation stage-dependent differences in crystallinity, molecular weight and molecular weight distribution of the PLA96 samples.

Rubber toughened linear and star-shaped poly(d,l-lactide-co-glycolide): synthesis, properties and in vitro degradation

Abstract Blends of d,l -lactide/glycolide copolymers were synthesized and their properties and in vitro degradation behaviour were evaluated as a function of chain architecture and blend composition. Tensile and impact properties of the blends are hardly influenced by matrix composition and chain architecture, but predominantly vary with the amount of rubber. In vitro degradation showed that hydrolytic degradation is enhanced by the incorporation of glycolide into the poly( d,l -lactide) matrix. Surprisingly, blends based on 6-arm star-shaped poly( d,l -lactide- co -glycolide) retain their mechanical properties for a longer period than blends with linear matrices of comparable composition. Physical aging of the linear copolymers is more severe and faster than that of star-shaped copolymers.

Supertough poly(lactide)s

SummarySemi-crystalline and amorphous copolymers of lactide and glycolide were rubber modified with degradable rubbers based on ε-caprolactone. The influence of crystallinity of the matrix, type of rubber and chain architecture on the impact resistance of the resulting materials was investigated. With a poly(l-lactide-co-ε-caprolactone) rubber semi-crystalline poly(lactide)s could be impact modified to a greater extent than amorphous non-crystallizable lactide matrices. Poly(trimethylene carbonate-co-ε-caprolactone) was used in blends and linear and star-shaped block copolymers which yield supertough materials that do not break in Izod notched impact testing. Rubber content appears critical around 20 weight percent, where a sharp transition is observed.

In vitro predegradation at elevated temperatures of poly(lactide)

In this study in vitro predegradation at elevated temperatures, used to obtain an increased degradation rate, was investigated. The in vitro degradation was followed by mass loss, molecular weight loss and changes in thermal properties. Two biodegradable polymers, the homopolymer PLLA and a copolymer PLA96 (96% L4%D lactide), were hydrolytically degraded at 90°C in a phosphate buffered solution. Both polymers, PLLA and PLA96, showed an initial linear degradation rate, but with longer implantation periods the degradation rate decreased and total degradation was best described as an asymptotic. Mass loss of the copolymer PLA96 was twice that of PLLA. The chemical analysis of the in vitro predegraded polymers coincided for both the decrease in molecular weight and the thermal properties with physiologically degraded poly(lactide). The results of this study show that although the degradation temperature is well above the glass transition temperature and not comparable to physiological temperatures, there seems to be good correlation between the in vitro degraded material and physiologically degraded material. In vitro predegradation enables investigation of the entire degradation process of a polymer in a short-term study. Moreover, in vitro predegradation allows direct comparison of the degradation rate of various polymers.

Poly (96L/4D-Lactide) implants for repair of orbital floor defects: an in vitro study of the material properties in a simulation of the human orbit

To test the mechanical and physical properties of two types of poly(96L/4D-lactide) (PLA96) implants and to evaluate their suitability for repair of large orbital floor defects, a study using an in vitro set-up was performed. Implants, 0.2 mm thick and 28 mm in diameter, were produced by either an extrusion process (type A) or by direct machining (type B) and had a molecular weight % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9qq-f0-yqaqVeLsFr0-vr% 0-vr0db8meaabaqaciGacaGaaeqabaWaaeaaeaaakeaacaqGOaWaa0% aaaeaacaWGnbaaamaaBaaaleaacaqG3baabeaakiaacMcaaaa!3CA8!\[{\text{(}}\overline M _{\text{w}} )\] of 64×103 and 146×103 g/mole, respectively, after γ-sterilization with a dose of 25 kGy. The implants were tested over 8 weeks in an apparatus simulating the human orbit with a 3.1 cm2 orbital floor defect under a static load corresponding to a retrobulbar pressure of 13 mm Hg as well as unloaded. Both implant types were able to counteract the applied static load without fracturing or excessive sagging. The type A implants sagged more than the type B implants (2.3±0.1 mm versus 1.0±0.0 mm, p<0.01) but retained and even increased their strength during the study whereas the type B implants showed a gradual strength-loss. In the clinical setting the observed sagging in both types would not have resulted in positional changes of the eyeball. It is concluded that with respect to the mechanical properties, both types of PLA96 implants tested are suitable for repair of large orbital floor defects.