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

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

Two Dimensional, Spatial Arrangement of Fibronectin Adsorbed to Biomaterials with Different Wettabilities

The effects of concentration, pH and substratum wettability on the two dimensional, spatial arrangement of adsorbed fibronectin are determined. Substrata with different wettability were exposed to a well defined flow of a fibronectin solution (0.1 or 1 mg/ml) in potassium phosphate buffer (pH 7.0 or 4.8) during 120 minutes at a shear rate of 20 s1. Rotary shadowed replicas of the surfaces were examined by transmission electron microscopy. Well defined structures, island-like in character on the low wettability substrata and knotted, reticulated on the high wettability substrata, could be seen in case of adsorption from pH 7.0 and the high concentration solution. Structures became more blurred upon lowering the solution pH and fibronectin concentration. Compared with bovine serum albumin, fibronectin shows smaller island-like structures, but the reticulated structure is thicker than for albumin

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

Preservation of the Cell-Biomaterial Interface at the Ultrastructural Level

Studying the tissue-biomaterial interface at the ultrastructural level is not without problems. Dissolution of the biomaterial in one of the dehydration or embedding media causes holes and shatter during sectioning or dislodgement of the biomaterial. The fine tuning of the hardness of both biomaterial and embedding medium, as well as the introduction of butyl-2,3- epoxypropylether as an intermediate between the dehydration series and the Epon resin , improving the impregnation , will solve many of the problems mentioned. With this improved technique good results were obtained with materials ranging from teflon, poly(Lactic acid) and polyurethanes to tissue culture polystyrene. No holes, shatter or dislodgement of the biomaterial was observed

Symptoms and functional status of patients with disseminated cancer visiting outpatient departments

Considerable research has focused on pain and other symptoms in terminal cancer patients referred to hospices and palliative care services. These patients differ from Dutch cancer patients in the palliative stage of their disease because the latter are cared for by general practitioners at home and medical specialists in outpatient departments. To clarify the experience of these Dutch patients, a study was started to investigate the prevalence and severity of pain and other symptoms as well as the functional status of consecutive patients visiting oncology outpatient departments for follow-up. After randomization, one group (I) of patients was interviewed at home by a general practitioner using structured questionnaires. The other group (II) received the questionnaires by mail, and scored the symptoms independently. The results of the symptom assessment show that patients in groups I and II suffered 2.4 (SD = 1.7) and 2.8 (SD = 2.0) symptoms, respectively. Between 30% and 40% of all patients reported constipation, nausea, loss of appetite, coughing, and dyspnea. These percentages were 50% lower when only moderate, severe, or extremely distressing symptoms were included. Sixty percent of all patients had pain, and 20% indicated a daytime pain score of 5 or greater on a scale of 0 to 10. Functional status was measured by the COOPWONCA charts; the mean score for the charts "physical fitness" and "daily activities" was 1.5 points lower for cancer patients than a random sample from the community of the same age and gender. The findings of this study should motivate doctors to put more energy in symptom assessment and interventions in palliative care. Record 29 of 32 - SilverPlatter MEDLINE(R)

Review: Biomaterials for Abdominal Wall Reconstruction

The reconstruction of large abdominal wall defects still is a major surgical problem. Many different techniques have been developed for this purpose, most of which appeared to be unsatisfactory. The lack of sufficient tissue requires the insertion of prosthetic material. Non-absorbable prostheses used to reconstruct abdominal wall defects showed the best results . Polypropylene mesh (PPM) and expanded polytetrafluoroethylene (ePTFE) soft-tissue patch are the most frequently used materials for this purpose . However, PPM induces extensive visceral adhesions and erosion of the skin, whereas ePTFE is insufficiently anchored to the adjacent tissue and therefore both materials are not ideal. As a result of own clinical and experimental studies , we constructed a new prosthesis that combines the favourable properties and avoids the drawbacks of PPM and ePTFE and tested it in an experimental study in the rat. The results are promising and warrant future study to find the ideal non -absorbable prosthesis to reconstruct large abdominal wall defects

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