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The overactive bladder is a condition characterized by a sudden urge to urinate, even with small volumes of urine present in the bladder. The current treatments available for this pathology consist on conservative approaches and the continuous administration of drugs, which when made by conventional methods has limitations related to the first pass metabolism, bioavailability, severe side effects, and low patient adherence to treatments, ultimately leading to low effectiveness. Within this context, the present work proposes the design, manufacture, and characterization of an intravesical implant for the treatment of overactive bladder pathology, using EVA copolymer as a matrix and oxybutynin as a drug. The fabrication of devices through two manufacturing techniques (extrusion and additive manufacturing by fused filament fabrication, FFF) and the evaluation of the implants through characterization tests was proposed. The usability and functionality were evaluated through simulated insertion of the device/prototype in a bladder model through catheter insertion tests. The safety and effectiveness of the devices was investigated from mechanical testing as well as drug release assays. Drug release assays presented a burst release in the first 24 h, followed by a release of 1.8 and 2.8 mg/d, totalizing 32 d. Mechanical tests demonstrated an increase in the stiffness of the specimens due to the addition of the drug, showing a change in maximum stress and strain at break. The released dose was higher than that usually presented when considering the oral administration route, showing the optimization of the development of this implant has the potential to improve the quality of life of patients with overactive bladder.

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PURPOSE: Endometriosis is a common chronic gynecological disease defined as the presence of endometrial glands and stroma tissue outside the uterus. Gestrinone is an effective antiestrogen that induces endometrial atrophy and/or amenorrhea. The purpose of this systematic review is to provide an evaluation of safety and effectiveness of gestrinone for the treatment of endometriosis. METHODS: We performed a search in six electronic databases: PubMed, MEDLINE (ovid), Embase, Cochrane CENTRAL (clinical trials), Web of Science and Scopus. Our selected primary outcomes were the changes in dysmenorrhea, pain relief including pelvic pain and dyspareunia. The secondary outcomes embrace hormones parameters, pregnancy rate and adverse events. RESULTS: Of 3269 references screened, 16 studies were included involving 1286 women. All studies compared gestrinone with other drugs treatments (placebo, Danazol, Mifepristone tablets, Leuprolide acetate, Quyu Jiedu Recipe) during 6 months. When compared with other drugs treatments, gestrinone relieved dysmenorrhea, pelvic pain, and morphologic response in the ovary. There was an increase on the pregnancy rate. Regarding the side effects observed, gestrinone showed the same adverse events and increased the risk of acne and seborrhea when compared to other treatments. Even if there was any difference in efficacy between gestrinone, danazol, leuprolide acetate, or Quyu Jiedu Recipe Chinese Medicine, it remains unclear due to insufficient data. CONCLUSION: Based limited evidence available suggests that gestrinone appeared to be safe and may have some efficacy advantages over danazol, as well as other therapeutic interventions for treating endometriosis. However, this conclusion should be interpreted with caution, due the quality of the evidence provided is generally very low or unclear. TRIAL REGISTRATION: CRD42021284148.

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Prior to clinical use, the corrosion resistance of new prosthesis system must be verified. The fretting-corrosion mechanisms of total hip arthroplasty (THA) implants generate metal debris and ions that can increase the incidence of adverse tissue reactions. For cemented stems, there are at least two interfaces that can be damaged by fretting-corrosion: stem-head and stem-cement. This investigation aimed to evaluate, through in vitro and in silico analyses, fretting-corrosion at the stem-head and stem-cement interfaces, to determine which surface is most affected in pre-clinical testing and identify the causes associated with the observed behavior. Unimodular stems and femoral heads of three different groups were evaluated, defined according to the head/stem material as group I (SS/SS), group II (CoCr/SS), and group III (CoCr/CoCr). Seven pairs of stems and heads per group were tested: three pairs were subjected to material characterization, three pairs to in vitro fretting-corrosion testing, and one pair to geometric modeling in the in silico analysis. The absolute area of the stem body degraded was more than three times higher compared with the trunnion, for all groups. These results were corroborated by the in silico analysis results, which revealed that the average micromotion at the stem-cement interface (9.65-15.66 µm) was higher than that at the stem-head interface (0.55-1.08 µm). In conclusion, the degradation of the stem-cement interface is predominant in the pre-clinical set, indicating the need to consider the fretting-corrosion at the stem-cement interface during pre-clinical implant evaluations.

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PURPOSE: (1) To evaluate the biomechanical properties of a porcine flexor digitorum superficialis tendon graft with preserved muscle fibers and (2) to compare these results with the biomechanical properties of a porcine tendon graft after removal of associated muscle. METHODS: Eighty-two porcine forelegs were dissected and the flexor digitorum superficialis muscle tendons were harvested. The study comprised of two groups: Group 1 (G1), harvested tendon with preserved muscle tissue; and Group 2 (G2), harvested contralateral tendon with removal of all muscle tissue. Tests in both groups were conducted using an electro-mechanical material testing machine (Instron, model 23-5S, Instron Corp., Canton, MA, USA) with a 500 N force transducer. Yield load, stiffness, and maximum load were evaluated and compared between groups. RESULTS: The behavior of the autografts during the tests followed the same stretching, deformation, and failure patterns as those observed in human autografts subjected to axial strain. There were no significant differences in the comparison between groups for ultimate load to failure (p = 0.105), stiffness (p = 0.097), and energy (p = 0.761). CONCLUSION: In this porcine model biomechanical study, using autograft tendon with preserved muscle showed no statistically significant differences for yield load, stiffness, or maximum load compared to autograft tendon without preserved muscle. The preservation of muscle on the autograft tendon did not compromise the mechanical properties of the autograft. LEVEL OF EVIDENCE: Level III Controlled laboratory study.

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PURPOSE: To provide a systematic map of the nature and extent of preclinical research concerning drug-releasing polymeric implants. SIGNIFICANCE: By summarizing available data, this mapping review can guide the development of new drug-delivery devices. METHODS: In-vitro studies assessing drug-delivery implants were reviewed. A study protocol was registered at Open Science Framework. The association of polymers with prominent drugs, manufacturing processes, geometries, treatments, and anatomical locations was assessed using the VOSviewer software. The release periods were also evaluated. RESULTS: A total of 423 articles, published between 1975 and 2020, were included and grouped into a framework with nine main categories. More than half of studies were published between 2010 and 2020. Among 201 individual polymers or combinations, the most investigated were PLGA, PCL, PLA, Silicone (SIL), EVA, and PU. Similarly, from 232 individual drugs or combinations, the most prominent were dexamethasone (DEX; anti-inflammatory), paclitaxel (PTX; anticancer), fluoruracil (anticancer), ciprofloxacin (CFX) hydrochloride (antibiotic), and gentamicin (GS; antibiotic). A total of 51 manufacturing processes were encountered, of which the most reported were solvent evaporation, compression molding (CM), extrusion (EX), electrospinning (ELS), and melt molding (MM). Among 38 implant geometries, cylinder (CIL) was the most prominent, followed by disk, square film, circular film (FCIR), and undefined film. Release times varied greatly, although the majority of articles ranged between 5 and 300 d. CONCLUSIONS: Drug-delivery implants were highly heterogeneous due to its applicability for multiple health conditions. Most implants were made of PLGA and most drugs assessed presented anti-inflammatory, antibiotic, or anticancer effects. Solvent evaporation and CIL were the most prominent manufacturing process and geometry, respectively.

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The transverse deformations of tendons assessed in tensile tests seems to constitute a controversial issue in literature. On the one hand, large positive variations of the Poisson's ratio have been reported, indicating volume reduction under tensile states. On the other hand, negative values were also observed, pointing out an auxetic material response. Based on these experimental observations, the following question is raised: Are these large and discrepant transverse deformations intrinsically related to the constitutive response of tendons or they result from artifacts of the mechanical test setup? In order to provide further insights to this question, an experimental and numerical study on the transverse kinematics of tendons was carried out. Tensile experiments were performed in branches of deep digital flexor tendons of domestic porcine, where the transverse displacements were measured by two high-speed, high-accuracy optical digital micrometers placed transversely to one another. Aiming at a better understanding of the effects of the mechanical test setup in the transverse measurements, a three-dimensional finite element model is proposed to resemble the tensile experiment. The main achieved results strongly support the following hypotheses regarding tensile tests of tendons: the clamping region considerably affects the kinematics of the specimen even at a large distance from the clamps; the transverse deformations are mainly ruled by stiff fibers embedded in a soft matrix; the generalization of the Poisson's ratio to draw conclusions about changes in volume of tendons may lead to misinterpretations.

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PURPOSE:: To evaluate the thermomechanical and in vitro biological response of poly(lactic-co-glycolic acid) (PLGA) plates for craniofacial reconstructive surgery. METHODS:: PLGA 85/15 craniofacial plates were produced by injection molding by testing two different temperatures (i.e., 240°C, PLGA_lowT, and 280°C, PLGA_highT). The mechanical properties of the produced plates were characterized by three-point bending tests, dynamic mechanical analysis, and residual stress. Crystallinity and thermal transitions were investigated by differential scanning calorimetry. Finally, in vitro cell interaction was evaluated by using SAOS-2 as cell model. Indirect cytotoxicity tests (ISO 10-993) were performed to prove the absence of cytotoxic release. Cells were then directly seeded on the plates and their viability, morphology, and functionality (ALP) checked up to 21 days of culture. RESULTS:: A similar performance of PLGA_lowT and PLGA_highT plates was verified in the three-point bending test and dynamic mechanical analyses. Also, the two processing temperatures did not influence the in vitro cell interaction. Cytotoxicity and ALP activity were similar for the PLGA plates and control. Cell results demonstrated that the PLGA plates supported cell attachment and proliferation. Furthermore, energy-dispersive X-ray spectroscopy revealed the presence of sub-micron particles, which were identified as inorganic mineral deposits resulting from osteoblast activity. CONCLUSION:: The present work demonstrated that the selected processing temperatures did not affect the material performance. PLGA plates showed good mechanical properties for application in craniofacial reconstructive surgery and adequate biological properties.

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