Mechanical characterization of porcine ureter for the evaluation of tissue-engineering applications.

Introduction: Clinics increasingly require readily deployable tubular substitutes to restore the functionality of structures like ureters and blood vessels. Despite extensive exploration of various materials, both synthetic and biological, the optimal solution remains elusive. Drawing on abundant literature experiences, there is a pressing demand for a substitute that not only emulates native tissue by providing requisite signals and growth factors but also exhibits appropriate mechanical resilience and behaviour. Methods: This study aims to assess the potential of porcine ureters by characterizing their biomechanical properties in their native configuration through ring and membrane flexion tests. In order to assess the tissue morphology before and after mechanical tests and the eventual alteration of tissue microstructure that would be inserted in material constitutive description, histological staining was performed on samples. Corresponding computational analyses were performed to mimic the experimental campaign to identify the constitutive material parameters. Results: The absence of any damages to muscle and collagen fibres, which only compacted after mechanical tests, was demonstrated. The experimental tests (ring and membrane flexion tests) showed non-linearity for material and geometry and the viscoelastic behaviour of the native porcine ureter. Computational models were descriptive of the mechanical behaviour ureteral tissue, and the material model feasible. Discussion: This analysis will be useful for future comparison with decellularized tissue for the evaluation of the aggression of cell removal and its effect on microstructure. The computational model could lay the basis for a reliable tool for the prediction of solicitation in the case of tubular substitutions in subsequent simulations.

How does sutures pattern influence stomach motility after endoscopic sleeve gastroplasty? A computational study.

The relatively recent adoption of Endoscopic Sleeve Gastroplasty (ESG) amongst obese patients has gained approval within the surgical community due to its notable benefits, including significant weight loss, safety, feasibility, repeatability, and potential reversibility. However, despite its promising clinical outcomes and reduced invasiveness, there is still a lack of standardised procedures for performing ESG. Multiple suture patterns and stitching methods have been proposed over time, yet rational tools to quantify and compare their effects on gastric tissues are absent. To address this gap, this study proposed a computational approach. The research involved a case study analyzing three distinct suture patterns (C-shaped, U-shaped and Z-shaped) using a patient-specific computational stomach model generated from magnetic resonance imaging. Simulations mimicked food intake by placing wire features in the intragastric cavity to replicate sutures, followed by applying a linearly increasing internal pressure up to 15 mmHg. The outcomes facilitated comparisons between suture configurations based on pressure-volume behaviours and the distribution of maximum stress on biological tissues, revealing the U-shaped as the more effective in terms of volume reduction, even if with reduced elongation strains and increased tissues stresses, whereas the Z-shaped is responsible of the greatest stomach shortness after ESG. In summary, computational biomechanics methods serve as potent tools in clinical and surgical settings, offering insights into aspects that are challenging to explore in vivo, such as tissue elongation and stress. These methods allow for mechanical comparisons between different configurations, although they might not encompass crucial clinical outcomes.

Ex vivo, in vivo and in silico studies of corneal biomechanics: a systematic review.

Healthy cornea guarantees the refractive power of the eye and the protection of the inner components, but injury, trauma or pathology may impair the tissue shape and/or structural organization and therefore its material properties, compromising its functionality in the ocular visual process. It turns out that biomechanical research assumes an essential role in analysing the morphology and biomechanical response of the cornea, preventing pathology occurrence, and improving/optimising treatments. In this review, ex vivo, in vivo and in silico methods for the corneal mechanical characterization are reported. Experimental techniques are distinct in testing mode (e.g., tensile, inflation tests), samples' species (human or animal), shape and condition (e.g., healthy, treated), preservation methods, setup and test protocol (e.g., preconditioning, strain rate). The meaningful results reported in the pertinent literature are discussed, analysing differences, key features and weaknesses of the methodologies adopted. In addition, numerical techniques based on the finite element method are reported, incorporating the essential steps for the development of corneal models, such as geometry, material characterization and boundary conditions, and their application in the research field to extend the experimental results by including further relevant aspects and in the clinical field for diagnostic procedure, treatment and planning surgery. This review aims to analyse the state-of-art of the bioengineering techniques developed over the years to study the corneal biomechanics, highlighting their potentiality to improve diagnosis, treatment and healing process of the corneal tissue, and, at the same, pointing out the current limits in the experimental equipment and numerical tools that are not able to fully characterize in vivo corneal tissues non-invasively and discourage the use of finite element models in daily clinical practice for surgical planning.

The suprapatellar fat pad: A histotopographic comparative study.

The suprapatellar fat pad is an adipose tissue located in the anterior knee whose role in osteoarthritis is still debated. Considering that anatomy drives function, the aim of this histotopographic study was to investigate the specific morphological features of the suprapatellar fat pad versus the infrapatellar fat pad in the absence of osteoarthritis, for a broad comparative analysis. Suprapatellar fat pad and infrapatellar fat pad tissue samples (n = 10/group) underwent microscopical/immunohistochemical staining and transmission electron microscopy analysis; thus, tissue-specific characteristics (i.e., vessels and nerve endings presence, lobuli, adipocytes features, septa), including extracellular matrix proteins prevalence (collagens, elastic fibers), were focused. Multiphoton microscopy was also adopted to evaluate collagen fiber orientation within the samples by Fast Fourier Transform (coherency calculation). The absence of inflammation was confirmed, and comparable counted vessels and nerve endings were shown. Like the infrapatellar fat pad, the suprapatellar fat pad appeared as a white adipose tissue with lobuli and septa of comparable diameter and thickness, respectively. Tissue main characteristics were also proved by both semithin sections and transmission electron microscopy analysis. The suprapatellar fat pad adipocytes were roundish and with a smaller area, perimeter, and major axis than that of the infrapatellar fat pad. The collagen fibers surrounding them showed no significant difference in collagen type I and significantly higher values for collagen type III in the infrapatellar fat pad group. Regarding the septa, elastic fiber content was statistically comparable between the two groups, even though more represented by the suprapatellar fat pad. Total collagen was significantly higher in the infrapatellar fat pad and comparing collagen type I and type III they were similarly represented in the whole cohort despite collagen type I appearing to be higher in the infrapatellar fat pad than in the suprapatellar fat pad and vice versa for collagen type III. Second harmonic generation microscopy confirmed through coherency calculation an anisotropic distribution of septa collagen fibers. From a mechanical point of view, the different morphological characteristics determined a major stiffness for the infrapatellar fat pad with respect to the suprapatellar fat pad. This study provides, for the first time, a topographic description of the suprapatellar fat pad compared to the infrapatellar fat pad; differences between the two groups may be attributed to a different anatomical location within the knee; the results gathered here may be useful for a more complete interpretation of osteoarthritis disease, involving not only cartilage but the whole joint.

Unveiling the effects of key factors in enhancing gastroesophageal reflux: A fluid-structure analysis before and after laparoscopic sleeve gastrectomy.

BACKGROUND AND OBJECTIVES: Gastro-oesophageal reflux disease (GERD) consists in the passage of gastric acid content from the stomach to the oesophagus, causing burns and deteriorating the quality of life. Laparoscopic Sleeve Gastrectomy (LSG) could induce de novo GERD and worsen pre-existing GERD because of the higher gastric pressurisation, reduction of stomach volume and a wider His-angle. In the proposed work, various computational gastric 2D models were developed to understand the effects of variables such as the His-angle, the antral dimension, and the bolus viscosity on the reflux increase. METHODS: Fluid-Structure Interaction (FSI) computational models which couple the solid mechanics of the gastric wall, and the fluid domain of the bolus, have been developed to shed light on biomechanical aspects of GERD after LSG. A closure was imposed to the lower oesophageal sphincter (LES) mimicking what happens physiologically after food intake. RESULTS: Results showed that the configuration prone to higher reflux flow was the post-surgical 65° model with a staple line starting directly from the pylorus without antral preservation, for all considered viscosities. Increasing viscosity, reflux flow decreased. Post-surgical refluxes were higher than pre-ones and decreased with increasing antrum preservation. CONCLUSIONS: These results could be a starting point for analysis of anatomical features, bariatric surgery and GERD occurrence. Further studies based on 3D geometries need to be performed.

Artificial sphincters: An overview from existing devices to novel technologies.

Artificial sphincters (ASs) are used to replace the function of the biological sphincters in case of severe urinary and fecal incontinence (UI and FI), and gastroesophageal reflux disease (GERD). The design of ASs is established on different mechanisms, e.g., magnetic forces or hydraulic pressure, with the final goal to achieve a implantable and durable AS. In clinical practice, the implantation of in-commerce AS is considered a reasonable solution, despite the sub-optimal clinical outcomes. The failure of these surgeries is due to the malfunction of the devices (between 46 and 51%) or the side effects on the biological tissues (more than 38%), such as infection and atrophy. Concentrating on this latter characteristic, particular attention has been given to the interaction between the biological tissues and AS, pointing out the closing mechanism around the duct and the effect on the tissues. To analyze this aspect, an overview of existing commercial/ready-on-market ASs for GERD, UI, and FI, together with the clinical outcomes available from the in-commerce AS, is given. Moreover, this invited review discusses ongoing developments and future research pathways for creating novel ASs. The application of engineering principles and design concepts to medicine enhances the quality of healthcare and improves patient outcomes. In this context, computational methods represent an innovative solution in the design of ASs, proving data on the occlusive force and pressure necessary to guarantee occlusion and avoid tissue damage, considering the coupling between different device sizes and individual variability.

Patient-specific stomach biomechanics before and after laparoscopic sleeve gastrectomy.

BACKGROUND: Obesity has become a global epidemic. Bariatric surgery is considered the most effective therapeutic weapon in terms of weight loss and improvement of quality of life and comorbidities. Laparoscopic sleeve gastrectomy (LSG) is one of the most performed procedures worldwide, although patients carry a nonnegligible risk of developing post-operative GERD and BE. OBJECTIVES: The aim of this work is the development of computational patient-specific models to analyze the changes induced by bariatric surgery, i.e., the volumetric gastric reduction, the mechanical response of the stomach during an inflation process, and the related elongation strain (ES) distribution at different intragastric pressures. METHODS: Patient-specific pre- and post-surgical models were extracted from Magnetic Resonance Imaging (MRI) scans of patients with morbid obesity submitted to LSG. Twenty-three patients were analyzed, resulting in forty-six 3D-geometries and related computational analyses. RESULTS: A significant difference between the mechanical behavior of pre- and post-surgical stomach subjected to the same internal gastric pressure was observed, that can be correlated to a change in the global stomach stiffness and a minor gastric wall tension, resulting in unusual activations of mechanoreceptors following food intake and satiety variation after LSG. CONCLUSIONS: Computational patient-specific models may contribute to improve the current knowledge about anatomical and physiological changes induced by LSG, aiming at reducing post-operative complications and improving quality of life in the long run.

Porcine Small Intestinal Submucosa (SIS) as a Suitable Scaffold for the Creation of a Tissue-Engineered Urinary Conduit: Decellularization, Biomechanical and Biocompatibility Characterization Using New Approaches.

Bladder cancer (BC) is among the most common malignancies in the world and a relevant cause of cancer mortality. BC is one of the most frequent causes for bladder removal through radical cystectomy, the gold-standard treatment for localized muscle-invasive and some cases of high-risk, non-muscle-invasive bladder cancer. In order to restore urinary functionality, an autologous intestinal segment has to be used to create a urinary diversion. However, several complications are associated with bowel-tract removal, affecting patients' quality of life. The present study project aims to develop a bio-engineered material to simplify this surgical procedure, avoiding related surgical complications and improving patients' quality of life. The main novelty of such a therapeutic approach is the decellularization of a porcine small intestinal submucosa (SIS) conduit to replace the autologous intestinal segment currently used as urinary diversion after radical cystectomy, while avoiding an immune rejection. Here, we performed a preliminary evaluation of this acellular product by developing a novel decellularization process based on an environmentally friendly, mild detergent, i.e., Tergitol, to replace the recently declared toxic Triton X-100. Treatment efficacy was evaluated through histology, DNA, hydroxyproline and elastin quantification, mechanical and insufflation tests, two-photon microscopy, FTIR analysis, and cytocompatibility tests. The optimized decellularization protocol is effective in removing cells, including DNA content, from the porcine SIS, while preserving the integrity of the extracellular matrix despite an increase in stiffness. An effective sterilization protocol was found, and cytocompatibility of treated SIS was demonstrated from day 1 to day 7, during which human fibroblasts were able to increase in number and strongly organize along tissue fibres. Taken together, this in vitro study suggests that SIS is a suitable candidate for use in urinary diversions in place of autologous intestinal segments, considering the optimal results of decellularization and cell proliferation. Further efforts should be undertaken in order to improve SIS conduit patency and impermeability to realize a future viable substitute.

Coupled experimental and computational approach to stomach biomechanics: Towards a validated characterization of gastric tissues mechanical properties.

Gastric diseases are one of the most relevant healthcare problems worldwide. Interventions and therapies definition/design mainly derive from biomedical and clinical expertise. Computational biomechanics, with particular regard to the finite element method, provides hard-to-measure quantities during in-vivo tests, such as strain and stress distribution, leading to a more comprehensive and promising approach to improve the effectiveness of many different clinical activities. However, reliable finite element models of biological organs require appropriate constitutive formulations of building tissues, whose parameters identification needs an experimental campaign consisting in different tests on human tissues and organs. The aim of the reported here research activities was the identification of mechanical properties of human gastric tissues. Human gastric specimens were tested at tissue, sub-structural and structural levels, by tensile, membrane indentation and inflation tests, respectively. On the other hand, animal experimentations on tissue layers from literature pointed out the mechanical response at sub-tissue level during tensile loading conditions. In detail, the analysis of experimental results at sub-tissue and tissue levels led to a fibre-reinforced visco-hyperelastic constitutive formulation and to the identification of gastric layers mechanical behaviour. Results from experimentations on human samples were coupled with data derived from animal models. Data from sub-structural and structural experimentations were exploited to upgrade and validate the constitutive formulations and parameters. The developed investigations led to a reliable constitutive framework of human gastric tissues that both describe stomach mechanical functionality and allow computational investigations. Indeed, the comparisons among average computational data and experimental medians provided the following RMSEs (Root Mean Square Errors): 0.89 N, 0.15 N for corpus and fundus during membrane indentation test, respectively, and 0.44 kPa during inflation test. Accounting for the magnitude of experimental and computational data, the RMSEs can be considered low and acceptable because they concerned biological samples. In fact, biological tissues and structures are affected by a high inherent inter-samples' variability, which is detectable in both the geometrical configuration and the mechanical behaviour. The specific values of the here reported RMSEs ensured the reliability of the achieved parameters and the quality of the overall developed procedure. Reliable computational models of the gastric district could become efficient clinical tools to find out the main crucial aspects of bariatric procedures, such as the mechanical stimulation of gastric mechano-receptors. Moreover, the methods of computational biomechanics will permit to run the preliminary tests of new and innovative bariatric procedures, on one hand, predicting the successful rate and the effectiveness, and, on other hand, reducing the use of animal testing.

Computational evaluation of laparoscopic sleeve gastrectomy.

LSG is one of the most performed bariatric procedures worldwide. It is a safe and effective operation with a low complication rate. Unsatisfactory weight loss/regain may occur, suggesting that the operation design could be improved. A bioengineering approach might significantly help in avoiding the most common complications. Computational models of the sleeved stomach after LSG were developed according to bougie size (range 27-54 Fr). The endoluminal pressure and the basal volume were computed at different intragastric pressures. At an inner pressure of 22.5 mmHg, the basal volume of the 54 Fr configuration was approximately 6 times greater than that of the 27 Fr configuration (57.92 ml vs 9.70 ml). Moreover, the elongation distribution of the gastric wall was assessed to quantify the effect on mechanoreceptors impacting satiety by differencing regions and layers. An increasing trend in elongation strain with increasing bougie size was observed in all cases. The most stressed region and layer were the antrum (approximately 25% higher stress than that in the corpus at 37.5 mmHg) and mucosa layer (approximately 7% higher stress than that in the muscularis layer at 22.5 mmHg), respectively. In addition, the pressure-volume behaviors were reported. Computational models and bioengineering methods can help to quantitatively identify some critical aspects of the "design" of bariatric operations to plan interventions, and predict and increase the success rate. Moreover, computational tools can support the development of innovative bariatric procedures, potentially skipping invasive approaches.

A finite element analysis for evaluating mandibular advancement devices.

Obstructive sleep apnoea (OSA) is a disorder characterised by complete or partial occlusion of the upper airway during sleep. Muscles relax during sleeping and collapse into the airway, closing the throat and prohibiting air flowing into the lungs. Different solutions have been adopted to manage the pathology to improve the life quality of affected patients. Mandibular advancement devices (MADs) are proven to be a compliant and successful therapy in the forward repositioning of the mandible to increase the upper airway volume. However, this method has some long-term adverse events that may affect the teeth and periodontal ligaments. This paper presents a finite element model to evaluate the MADs effects (displacement and stress) on teeth and periodontal ligaments, by varying the design, the point of application of the force and the material. The modelled bodies have been reconstructed through a Reverse Engineering approach and computer-aided design tools starting from tomographic images of anatomic bodies and from laser scans of a physical MAD. The results suggest that a central connection mechanism could affect mostly the anterior teeth. In contrast, a lateral connection mechanism provides a more uniform distribution of the load on teeth.

Biomechanical Investigation of the Stomach Following Different Bariatric Surgery Approaches.

BACKGROUND: The stomach is a hollow organ of the gastrointestinal tract, on which bariatric surgery (BS) is performed for the treatment of obesity. Even though BS is the most effective treatment for severe obesity, drawbacks and complications are still present because the intervention design is largely based on the surgeon's expertise and intraoperative decisions. Bioengineering methods can be exploited to develop computational tools for more rational presurgical design and planning of the intervention. METHODS: A computational mechanical model of the stomach was developed, considering the actual complexity of the biological structure, as the nonhomogeneous and multilayered configuration of the gastric wall. Mechanical behavior was characterized by means of an anisotropic visco-hyperelastic constitutive formulation of fiber-reinforced conformation, nonlinear elastic response, and time-dependent behavior, which assume the typical features of gastric wall mechanics. Model applications allowed for an analysis of the influence of BS techniques on stomach mechanical functionality through different computational analyses. RESULTS: Computational results showed that laparoscopic sleeve gastrectomy and endoscopic sleeve gastroplasty drastically alter stomach capacity and stiffness, while laparoscopic adjustable gastric banding modestly affects stomach stiffness and capacity. Moreover, the mean elongation strain values, which are correlated to the mechanical stimulation of gastric receptors, were elevated in laparoscopic adjustable gastric banding compared to other procedures. CONCLUSIONS: The investigation of stomach mechanical response through computational models provides information on different topics such as stomach capacity and stiffness and the mechanical stimulation of gastric receptors, which interact with the brain to control satiety. These data can provide reliable support to surgeons in the presurgical decision-making process.

Biomechanics of stomach tissues and structure in patients with obesity.

Even though bariatric surgery is one of the most effective treatment option of obesity, post-surgical weight loss is not always ensured, especially in the long term, when many patients experience weight regain. Bariatric procedures are largely based on surgeon's expertise and intra-operative decisions, while an integrated in-silico approach could support surgical activity. The effects of bariatric surgery on gastric distension, which activates the neural circuitry promoting satiety, can be considered one of the main factors in the operation success. This aspect can be investigated trough computational modelling based on the mechanical properties of stomach tissues and structure. Mechanical tests on gastric tissues and structure from people with obesity are carried out, as basis for the development of a computational model. The samples are obtained from stomach residuals explanted during laparoscopic sleeve gastrectomy interventions. Uniaxial tensile and stress relaxation tests are performed in different directions and inflation tests are carried out on the entire stomach residual. Experimental results show anisotropic, non-linear elastic and time-dependent behavior. In addition, the mechanical properties demonstrate to be dependent on the sample location within the stomach. Inflation tests confirm the characteristics of time-dependence and non-linear elasticity of the stomach wall. Experimental activities developed provide a unique set of data about the mechanical behavior of the stomach of patients with obesity, considering both tissues and structure. This data set can be adopted for the development of computational models of the stomach, as support to the rational investigation of biomechanical aspects of bariatric surgery.

Computational Biomechanics: In-Silico Tools for the Investigation of Surgical Procedures and Devices.

Biomechanical investigations of surgical procedures and devices are usually developed by means of human or animal models. The exploitation of computational methods and tools can reduce, refine, and replace (3R) the animal experimentations for scientific purposes and for pre-clinical research. The computational model of a biological structure characterizes both its geometrical conformation and the mechanical behavior of its building tissues. Model development requires coupled experimental and computational activities. Medical images and anthropometric information provide the geometrical definition of the computational model. Histological investigations and mechanical tests on tissue samples allow for characterizing biological tissues' mechanical response by means of constitutive models. The assessment of computational model reliability requires comparing model results and data from further experimentations. Computational methods allow for the in-silico analysis of surgical procedures and devices' functionality considering many different influencing variables, the experimental investigation of which should be extremely expensive and time consuming. Furthermore, computational methods provide information that experimental methods barely supply, as the strain and the stress fields that regulate important mechano-biological phenomena. In this work, general notes about the development of biomechanical tools are proposed, together with specific applications to different fields, as dental implantology and bariatric surgery.

Anisotropic computational modelling of bony structures from CT data: An almost automatic procedure.

BACKGROUND AND OBJECTIVE: The use of modelling techniques that combine CT data and bone tissue micromechanics is spreading in computational biomechanics. Finite Element models show great potential in surgical planning of intervention and in prediction of stress and strain fields through a non-invasive method. The main challenge pertains to the reliable characterization of bone mechanical behaviour. An almost automatic procedure is here defined, which provides computational models of bony structures considering the actual anisotropy of bone tissue response. The innovative aspect resides on the automatic detection of the directions of anisotropy as the eigenvectors of a three-dimensional distribution matrix of HU values. METHODS: The procedure combines CT data and micromechanics modelling techniques. Regarding a specific location, the procedure reports both the orthotropic elastic constants, by the analysis of the local HU value, and the anisotropic material directions, by the analysis of the HU values distribution around the specific location. RESULTS: The procedure returns the distribution of bone tissue orthotropic elasticity tensor. The procedure proves to correctly respect the differentiation between cortical and trabecular bone. Principal directions show to be consistent with experimental data from ultrasound measurements. Regarding the material mapping from voxel to FE model, the developed strategies show to be reliable, leading to marginal errors (lower than 10%) for most of CT voxels (more than 90%). The computational analyses of typical structural loading conditions lead to strain values that are comparable with results from strain gauges experimentations. The development and the exploitation of FE models of different bony structures allow assessing the reliability of the procedure for cortical bone. CONCLUSIONS: The results highlight the potentialities of the procedure in providing accurate patient-specific biomechanical models of bony structures starting from CT data. The accuracy and the automatism of the procedure are important factors for the development of real time clinical tools. The main limitations of this work remain the not fully automatism and the reliability assessment, which is based mainly on cortical bone regions only.

Computational Models for the Mechanical Investigation of Stomach Tissues and Structure.

Bariatric surgery is performed on obese people aiming at reducing the capacity of the stomach and/or the absorbing capability of the gastrointestinal tract. A more reliable and effective approach to bariatric surgery may integrate different expertise, in the areas of surgery, physiology and biomechanics, availing of a strong cooperation between clinicians and engineers. This work aimed at developing a computational model of the stomach, as a computational tool for the physio-mechanical investigation of stomach functionality and the planning of bariatric procedures. In this sense, coupled experimental and numerical activities were developed. Experimental investigations on pig and piglet stomachs aimed at providing information about stomach geometrical configuration and structural behavior. The computational model was defined starting from the analysis of data from histo-morphometric investigations and mechanical tests. A fiber-reinforced visco-hyperelastic constitutive model was developed to interpret the mechanical response of stomach tissues; constitutive parameters were identified considering mechanical tests at both tissue and structure levels. Computational analyses were performed to investigate the pressure-volume behavior of the stomach. The developed model satisfactorily interpreted results from experimental activities, suggesting its reliability. Furthermore, the model was exploited to investigate stress and strain fields within gastric tissues, as the stimuli for mechanoreceptors that interact with the central nervous system leading to the feeling of satiety. In this respect, the developed computational model may be employed to evaluate the influence of bariatric intervention on the stimulation of mechanoreceptors, and the following meal induced satiety.