Development and characterization of 3D printed ethylene vinyl acetate (EVA) as drug delivery device for the treatment of overactive bladder.

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.

Tether pre-tension within vertebral body tethering reduces motion of the spine and influences coupled motion: a finite element analysis.

Anterior Vertebral Body Tethering (VBT) is a novel fusionless treatment option for selected adolescent idiopathic scoliosis patients which is gaining widespread interest. The primary objective of this study is to investigate the effects of tether pre-tension within VBT on the biomechanics of the spine including sagittal and transverse parameters as well as primary motion, coupled motion, and stresses acting on the L2 superior endplate. For that purpose, we used a calibrated and validated Finite Element model of the L1-L2 spine. The VBT instrumentation was inserted on the left side of the L1-L2 segment with different cord pre-tensions and submitted to an external pure moment of 6 Nm in different directions. The range of motion (ROM) for the instrumented spine was measured from the initial post-VBT position. The magnitudes of the ROM of the native spine and VBT-instrumented with pre-tensions of 100 N, 200 N, and 300 N were, respectively, 3.29°, 2.35°, 1.90° and 1.61° in extension, 3.30°, 3.46°, 2.79°, and 2.17° in flexion, 2.11°, 1.67°, 1.33° and 1.06° in right axial rotation, and 2.10°, 1.88°, 1.48° and 1.16° in left axial rotation. During flexion-extension, an insignificant coupled lateral bending motion was observed in the native spine. However, VBT instrumentation with pre-tensions of 100 N, 200 N, and 300 N generated coupled right lateral bending of 0.85°, 0.81°, and 0.71° during extension and coupled left lateral bending of 0.32°, 0.24°, and 0.19° during flexion, respectively. During lateral bending, a coupled extension motion of 0.33-0.40° is observed in the native spine, but VBT instrumentation with pre-tensions of 100 N, 200 N, and 300 N generates coupled flexion of 0.67°, 0.58°, and 0.42° during left (side of the implant) lateral bending and coupled extension of 1.28°, 1.07°, and 0.87° during right lateral bending, respectively. Therefore, vertebral body tethering generates coupled motion. Tether pre-tension within vertebral body tethering reduces the motion of the spine.

Biomechanical comparison of shoelace suture technique for repairing calcaneal tendon.

BACKGROUND: The biomechanical assessment of tendon repair is essential for the evaluation of different tendon suturing techniques. The shoelace suture technique with absorbable Vicryl® is a modified technique of Achilles tendon repair that may have biomechanical advantages depending on the number of threads used and the direction of the suture. PURPOSE: To evaluate the creep under constant pre-load, the stiffness, the maximum strength, and the failure mode for three different configurations of the shoelace suture in a bovine tendon biomechanical model. STUDY DESIGN: Controlled Laboratory Study. METHODS: 36 bovine Achilles tendon specimens were acquired and divided into three test groups of 12 Achilles tendons each. A model of the calcaneal tendon rupture was created through a transverse cut with a scalpel, performed 5 centimeters proximal to the calcaneal bone insertion. Group 1 was repaired using the simple shoelace technique with just one suture. Group 2 was repaired using the shoelace technique with three sutures individually sutured from distal to proximal at the site of rupture. Group 3 was repaired using the shoelace technique with three sutures individually sutured from proximal to distal at the site of rupture. RESULTS: System creep after constant pre-load was 5.9 ± 2.5 mm, 3.0 ± 0.4 mm and 2.9 ± 0.4 mm for groups 1, 2 and 3, respectively. The system's stiffness was 23.2 ± 2.8 N/mm, 30.3 ± 1.1 N/mm and 29.8 ± 2.3 N/mm for groups 1, 2 and 3, respectively. In the final load-to-failure test, the ultimate load force (ULF) was 158.2 ± 27.5 N, 346.5 ± 47.6 N and 358.1 ± 41.6 N for groups 1, 2 and 3, respectively. There was statistical significance in the comparative tests between groups 1-2 and 1-3 in terms of means of creep, system stiffness and maximum system strength. No statistically significant difference was found between groups 2 and 3 when analyzing creep, system stiffness and ULF. Suture breakage was the prevalent mode of failure for all tested groups. CONCLUSION: The shoelace with three sutures significantly reduced creep in the preloading phase and increased the stiffness and ultimate load force. The biomechanical results demonstrate better overall mechanical performance of the technique than the simple shoelace technique. The better mechanical performance indicates that the shoelace with three sutures could result in early postoperative rehabilitation. CLINICAL RELEVANCE: This study indicates that the shoelace suture technique with three sutures is biomechanically strong and stiff, being a possible therapeutic option to be used.

Evaluation of safety and effectiveness of gestrinone in the treatment of endometriosis: a systematic review and meta-analysis.

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.

Pre-clinical evaluation of fretting-corrosion at stem-head and stem-cement interfaces of hip implants using in vitro and in silico models.

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.

Tendon grafts with preserved muscle demonstrate similar biomechanical properties to tendon grafts stripped of muscular attachments: a biomechanical evaluation in a porcine model.

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.

Polymeric implants with drug-releasing capabilities: a mapping review of laboratory research.

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.

Thermomechanical and in vitro biological characterization of injection-molded PLGA craniofacial plates.

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.

An experimental and numerical study on the transverse deformations in tensile test of tendons.

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.