In Vivo Evaluation of the Efficacy and Safety of a Novel Degradable Polymeric Film for the Prevention of Intrauterine Adhesions.

STUDY OBJECTIVE: To study the safety of a degradable polymeric film (DPF) and its efficacy on reducing the risk of intrauterine-adhesion (IUA) formation in a rat model. DESIGN: A series of case-control studies relying on random allocation, where feasible. SETTING: University and good practice animal laboratories. ANIMALS: The animal models comprised female and male Oncins France Strain A and female Wistar rats. INTERVENTION(S) AND MEASUREMENTS: The Oncins France Strain A rats were used for in vivo evaluation of the impact of the DPF on endometrial thickness and its effect on fertility. For in vivo evaluation of the biologic response, 40 Wistar rats were randomly allocated to intervention and control groups, with matched sampling time after surgery. Finally, for the in vivo evaluation of the DPF's efficacy on IUA prevention, a total of 24 Wistar rats were divided into 3 groups: 1 treated with the DPF, 1 treated with hyaluronic acid gel, and a sham group. MAIN RESULTS: The DPF did not have a significant impact on endometrial thickness, and there were no significant differences in the number of conceived or prematurely terminated pregnancies, confirming its noninferiority to no treatment. The DPF did not induce irritation at 5 days and 28 days. Finally, the DPF significantly reduced the likelihood of complete IUA formation compared with hyaluronic acid gel- and sham-implanted animals, where only 27% of the animals had their uterine cavity obliterated compared with 80% and 100%, respectively. CONCLUSION: The DPF is a safe film that is effective in preventing IUA formation after intrauterine curettage in rats.

Relevance of selective neural stimulation with a multicontact cuff electrode using multicriteria analysis.

Neural multicontact cuff electrodes have the potential to activate selectively different groups of muscles and offer more possibilities of electrical configurations compared to whole ring cuffs. Several previous studies explored multicontact electrodes with a limited set of configurations which were sorted using a selectivity index only. The objective of the present study is to classify a larger number of configurations, i.e. the way the current is spread over the 12 contacts of the cuff electrode, using additional criteria such as robustness (i.e. ability to maintain selectivity within a range of current amplitudes) and efficiency (i.e. electrical consumption of the considered multipolar configuration versus the electrical consumption of the reference whole-ring configuration). Experiments were performed on the sciatic nerve of 4 rabbits. Results indicated that the optimal configuration depends on the weights applied to selectivity, robustness and efficiency criteria. Tripolar transverse is the most robust configuration and the less efficient, whereas tripolar longitudinal ring is efficient but not robust. New configurations issued from a previous theoretical study we carried out such as steering current ring appears as good compromise between the 3 criteria.

Preliminary design of a new degradable medical device to prevent the formation and recurrence of intrauterine adhesions.

Intrauterine adhesions lead to partial or complete obliteration of the uterine cavity and have life-changing consequences for women. The leading cause of adhesions is believed to be loss of stroma resulting from trauma to the endometrium after surgery. Adhesions are formed when lost stroma is replaced by fibrous tissue that join the uterine walls. Few effective intrauterine anti-adhesion barriers for gynecological surgery exist. We designed a degradable anti-adhesion medical device prototype to prevent adhesion formation and recurrence and restore uterine morphology. We focused on ideal degradation time for complete uterine re-epithelialization for optimal anti-adhesion effect and clinical usability. We developed a triblock copolymer prototype [poly(lactide) combined with high molecular mass poly(ethylene oxide)]. Comparative pre-clinical studies demonstrated in vivo anti-adhesion efficacy. Ease of introduction and optimal deployment in a human uterus confirmed clinical usability. This article provides preliminary data to develop an intrauterine medical device and conduct a clinical trial.

A new bioabsorbable polymer film to prevent peritoneal adhesions validated in a post-surgical animal model.

BACKGROUND: Peritoneal adhesions are a serious surgical postoperative complication. The aim of this study is to investigate, in a rat model, the anti-adhesive effects of a bioabsorbable film of polymer combining polyethylene glycol and polylactic acid. MATERIALS AND METHODS: Sixty-three animals were randomized into five groups according to the anti-adhesion treatment: Hyalobarrier®, Seprafilm®, Polymer A (PA), Polymer B (PB), and control. The rats were euthanized on days 5 and 12 to evaluate the extent, severity and degree of adhesions and histopathological changes. Three animals were euthanized at day 2 in PA, PB and control groups to observe the in vivo elimination. RESULTS: Macroscopic adhesion formation was significantly lower in the PA group than in the control group at day 5 (median adhesion score 0±0 vs 9.6 ±0.5 p = 0.002) and at day 12 (0±0 vs 7.3±4 p = 0.02). Furthermore, median adhesion score at day 5 was significantly lower in the PA group than in the Seprafilm group (0±0 vs 4.2± 3.9 p = 0.03). Residence time of PA seems longer than PB. CONCLUSION: The PA bioabsorbable film seems efficient in preventing the formation of peritoneal adhesions.

A New Rat Model for Translational Research in Bone Regeneration.

The European Union (EU) directive 2010/63/EU on the protection of animals used for scientific purpose focused on reducing the number of animals and refinement of breeding. Animal studies are necessary to protect human health. Lots of animal models exist to study bone regeneration, but a reliable, well reproducible, and relatively inexpensive model with the possibility for multiple testing in the same animal is still missing. Rats may serve as good models for this due to the small animal size and good cost/benefit ratio. The present study aimed to develop a novel rat caudal vertebrae critical size defect model for bone regeneration and implant osseointegration studies The study was performed using Wistar rats with weight from 380 to 450 g. An incision was made on the dorsal side of the tail. After skin and muscles retractions, the vertebrae were exposed. Critical size defects for bone tissue engineering or implant placements for titanium body experiments were possible in each of the first four caudal vertebrae. Micro-computed tomography (CT) and histology were used to detect bone growth. There was no bone formation in the defects after 1 or 2 months of healing. When a calcium phosphate biomaterial was used (Bio-Oss®; Geistlich Pharma AG, Wolhusen, Switzerland), a good stability of the material in the defect was noted and bone growth was visible after 1 or 2 months. Results based on implant placement showed good primary stability after 3 months of healing. MicroCT showed integrated implant position through the vertebra. These results suggest that the rat caudal vertebrae may serve as a good new model for studying bone regeneration and implant osseointegration with the possibility of multiple testing within the same experimental animal and the potential to decrease number of experimental animals.

Smooth muscle modeling and experimental identification: application to bladder isometric contraction.

This paper presents an original smooth muscle model based on the Huxley microscopic approach. This model is the main part of a comprehensive lower urinary track model. The latter is used for simulation studies and is assessed through experiments on rabbits, for which a subset of parameters is estimated, using intravesical pressure measurements in isometric conditions. Bladder contraction is induced by electrical stimulation that determines the onset and thus synchronizes simulation and experimental data. Model sensitivity versus parameter accuracy is discussed and allows the definition of a subset of four parameters that must be accurately identified in order to obtain good fitting between experimental and acquired data. Preliminary experimental data are presented as well as model identification results. They show that the model is able to follow the pressure changes induced by an artificial stimulus in isometric contractions. Moreover, the model gives an insight into the internal changes in calcium concentration and the ratio of the different chemical species present in the muscle cells, in particular the bounded and unbounded actin and myosin and the normalized concentration of intracellular calcium.