Enzymatic activity toward poly(L-lactic acid) implants

Tissue reactions toward biodegradable poly(L-lactic acid) implants were monitored by studying the activity pattern of seven enzymes as a function of time: alkaline phosphatase, acid phosphatase, -naphthyl acetyl esterase, -glucuronidase, ATP-ase, NADH-reductase, and lactate dehydrogenase. Cell types were identified by their specific enzyme patterns, their morphology and location. Special attention was paid to the enzyme patterns of macrophages, fibroblasts and polymorphonuclear granulocytes (PMNs), being involved in foreign body reactions or inflammatory responses. One day after implantation, an influx of neutrophilic and eosinophilic granulocytes was observed, coinciding with activity of alkaline phosphatase (PMN's) and -glucuronidase (eosinophils). From day 3 on, macrophages containing ATP-ase, acid phosphatase and esterase could be observed. From day 7 on, lactate dehydrogenase, the enzyme normally involved in the conversion of lactic acid, and its coenzyme NADH-reductase were observed in macrophages and fibroblasts. These two enzymes demonstrated more activity than expected on basis of wound-healing reactions upon implantation of a nonbiodegradable, inert biomaterial (as, e.g., Teflon). It is concluded that the biodegradable poly (L-lactic acid) used in these implantation studies is tissue compatible, and evokes a foreign body reaction with minor macrophage and giant cell activity, as observed during this 3-week implantation period. Most enzyme patterns were simply due to a wound-healing reaction. The slightly increased levels of LDH and NADH suggest the release of lactic acid from the implant, and thus confirms the biodegradable nature of this polymer

Testing the Within-State Distribution in Mixture Models for Responses and Response Times

Mixture models have been developed to enable detection of within-subject differences in responses and response times to psychometric test items. To enable mixture modeling of both responses and response times, a distributional assumption is needed for the within-state response time distribution. Since violations of the assumed response time distribution may bias the modeling results, choosing an appropriate within-state distribution is important. However, testing this distributional assumption is challenging as the latent within-state response time distribution is by definition different from the observed distribution. Therefore, existing tests on the observed distribution cannot be used. In this article, we propose statistical tests on the within-state response time distribution in a mixture modeling framework for responses and response times. We investigate the viability of the newly proposed tests in a simulation study, and we apply the test to a real data set

Biodegradable hollow fibres for the controlled release of drugs

Biodegradable hollow fibres of poly-l-lactic acid (PLLA) filled with a suspension of the contraceptive hormone levonorgestrel in castor oil were implanted subcutaneously in rats to study the rate of drug release, rate of biodegradation and tissue reaction caused by the implant. The in vivo drug release was compared with the release in vitro using different release media. Fibres, disinfected with alcohol showed a zero-order release, both in vitro and in vivo, for over 6 months. Fibres, either γ-sterilized or disinfected with alcohol were harvested at time intervals ranging from 1 d to 6 months after implantation. Molecular weights of PLLA, tensile strengths, and remaining amounts of drug were determined as a function of time.\ud \ud The tissue reaction can be described as a very moderate foreign body reaction with the initial presence of macrophages, which are gradually replaced by fibroblasts which form a collagen capsule. Molecular weight determinations of PLLA showed a decrease from an initial Mw of 1.59x10 5 to 5.5 × 10 4 in 4 months (after alcohol sterilization). A gradual decrease in fibre strength with time was observed which did not significantly impair the release rate of levonorgestrel

Adhesion and spreading of cultured endothelial cells on modified and unmodified poly(ethylene terephthalate): a morphological study

The in vitro adhesion and spreading of human endothelial cells (HEC) on hydrophobic poly(ethylene terephthalate) (PETP) and moderately wettable tissue culture polyethylene terephthalate) (TCPETP) were studied with light microscopy and electron microscopy. Numbers of HEC adhering on TCPETP were always higher than those found on PETP. When cells were seeded in the presence of serum, extensive cell spreading on both PETP and TCPETP was observed after the first 30 min. Thereafter, spread cells appeared to withdraw from the PETP surface, resulting in irregularly shaped cells. Complete cell spreading occurred on TCPETP. Complete cell spreading also occurred on PETP and TCPETP when HEC had first been seeded from phosphate buffer solution and serum was supplied after 30 min. Furthermore, HEC spread on both PETP and TCPETP when the surfaces were precoated with protein(s), which promotes cell adhesion. However, when plasma was used for the coating, spread cells did not proliferate in a monolayer pattern. This study shows that TCPETP is, in general, a better surface for adhesion and proliferation of HEC than is PETP, suggesting that vascular prostheses with a TCPETP-like surface will perform better in vivo than prostheses made of PETP

In vivo and in vitro degradation of glycine/DL-lactic acid copolymers

A series of copolymers of glycine and DL-lactic acid with various compositions was synthesized and their in vivo and in vitro degradation behavior was studied. For the in vivo examination, discs of the copolymer films were subcutaneously implanted in rats. The in vitro studies were carried out in phosphate buffer at pH = 7.4 and 37°C. The decrease in molecular weight, the loss of weight, and the tissue reactions of the different copolymers were determined after 2, 5, and 10 weeks. Poly(DL-lactic acid) was used as reference material. The in vivo and in vitro degradation behavior of the polymers was comparable. The decrease of molecular weight of the copolymers and poly(DL-lactic acid) in time was similar. The weight loss for copolymers with a higher mole fraction of glycine units started earlier. The copolymer with the highest content of glycine units disappeared completely within 10 weeks both in vivo and in vitro. The poly(DL-lactic acid) implant lost only 25% weight over the same period. Tissue reactions against all materials started with an acute inflammatory reaction caused by the trauma of implantation, followed by wound-healing processes, ending in a very mild foreign body reaction for the poly(DL-lactic acid) and a more excessive macrophage mediated foreign body reaction for the glycine/DL-lactic acid copolymers. The tissue reaction was more severe for polymers having a higher rate of degradation