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Abstract Background Melting corneal ulcers are a serious condition that affects a great number of animals and people around the world and it is characterised by a progressive weakening of the tissue leading to possible severe ophthalmic complications, such as visual impairment or blindness. This disease is routinely treated with medical therapy and keratoplasty, and recently also with alternative regenerative therapies, such as cross-linking, amniotic membrane transplant, and laser. Plasma medicine is another recent example of regenerative treatment that showed promising results in reducing the microbial load of corneal tissue together with maintaining its cellular vitality. Since the effect of helium plasma application on corneal mechanical viscoelasticity has not yet been investigated, the aim of this study is first to evaluate it on ex vivo porcine corneas for different exposition times and then to compare the results with previous data on cross-linking treatment. Results 94 ex vivo porcine corneas divided into 16 populations (healthy or injured, fresh or cultured and treated or not with plasma or cross-linking) were analysed. For each population, a biomechanical analysis was performed by uniaxial stress-relaxation tests, and a statistical analysis was carried out considering the characteristic mechanical parameters. In terms of equilibrium normalised stress, no statistically significant difference resulted when the healthy corneas were compared with lesioned plasma-treated ones, independently of treatment time, contrary to what was obtained about the cross-linking treated corneas which exhibited more intense relaxation phenomena. Conclusions In this study, the influence of the Helium plasma treatment was observed on the viscoelasticity of porcine corneas ex vivo, by restoring in lesioned tissue a degree of relaxation similar to the one of the native tissue, even after only 2 min of application. Therefore, the obtained results suggest that plasma treatment is a promising new regenerative ophthalmic therapy for melting corneal ulcers, laying the groundwork for further studies to correlate the mechanical findings with corneal histology and ultrastructural anatomy after plasma treatment.

The production of biomedical devices able to appropriately interact with the biological environment is still a great challenge. Synthetic materials are often employed, but they fail to replicate the biological and functional properties of native tissues, leading to a variety of adverse effects. Several commercial products are based on chemically treated xenogeneic tissues: their principal drawback is due to weak mechanical stability and low durability. Recently, decellularization has been proposed to bypass the drawbacks of both synthetic and biological materials. Acellular materials can integrate with host tissues avoiding/mitigating any foreign body response, but they often lack sufficient patency and impermeability. The present paper investigates an innovative approach to the realization of hybrid materials that combine decellularized bovine pericardium with polycarbonate urethanes. These hybrid materials benefit from the superior biocompatibility of the biological tissue and the mechanical properties of the synthetic polymers. They were assessed from physicochemical, structural, mechanical, and biological points of view; their ability to promote cell growth was also investigated. The decellularized pericardium and the polymer appeared to well adhere to each other, and the two sides were distinguishable. The maximum elongation of hybrid materials was mainly affected by the pericardium, which allows for lower elongation than the polymer; this latter, in turn, influenced the maximum strength achieved. The results confirmed the promising features of hybrid materials for the production of vascular grafts able to be repopulated by circulating cells, thus, improving blood compatibility.

Background: Nowadays, a challenging task concerns the biomechanical study of the human lower urinary tract (LUT) due to the variety of its tissues and the low availability of samples. Methods: This work attempted to further extend the knowledge through a comprehensive mechanical characterization of the male LUT by considering numerous tissues harvested from the same cadaver, including some never studied before. Samples of the bladder, urethra, prostate, Buck’s fascia and tunica albuginea related to corpora cavernosa were considered and distinguished according to testing direction, specimen conformation and anatomical region. Uniaxial tensile and indentation tests were performed and ad hoc protocols were developed. Results: The tissues showed a non-linear and viscoelastic response but different mechanical properties due to their specific functionality and microstructural configuration. Tunica albuginea longitudinally displayed the highest stiffness (12.77 MPa), while the prostate transversally had the lowest one (0.66 MPa). The minimum stress relaxation degree (65.74%) was reached by the tunica albuginea and the maximum (88.55%) by the bladder. The prostate elastic modulus was shown to vary according to the presence of pathological changes at the microstructure. Conclusions: This is the first experimental work that considers the mechanical evaluation of the LUT tissues in relation to the same subject, setting the basis for future developments by expanding the sample population and for the development of effective in silico models to improve the solutions for most LUT pathologies.

Urinary incontinence is still an underestimated problem due to its anatomical complexity and social taboo. Most of the time, it is believed to affect predominantly the elderly female population, and the literature still lacks data on its presence in the younger and male populations. Its relationship with other pelvic floor dysfunctions (PFDs) and sport activity remains an open topic. Thus, the present study surveyed 342 subjects of both genders, ranging from 18 to 39 y/o and with different sport activity levels, to understand the prevalence of PFDs (such as haemorrhoids, anal fissures, involuntary urinary/faecal leakage, and urgency). The results also showed a significative prevalence in younger, sporty, and male people. Approximately one third of the population had urinary incontinence mostly during stress activities (sport activity: 17%, cough/sneeze: 13%). The statistical analysis confirmed a higher prevalence in the cases of a light (32%) and intense (41%) sport activity level and a protective role of sport if practiced between 5 and 10 h/week, with bodybuilding/CrossFit and running seeming to be the riskiest sports. The relationship with the other PFDs showed a statistically significant dependence with most of them, confirming that urinary incontinence cannot be considered a separate problem from the other PFDs.

Plantar adipose tissue is a connective tissue whose structural configuration changes according to the foot region (rare or forefoot) and is related to its mechanical role, providing a damping system able to adsorb foot impact and bear the body weight. Considering this, the present work aims at fully describing the plantar adipose tissue’s behaviour and developing a proper constitutive formulation. Unconfined compression tests and indentation tests have been performed on samples harvested from human donors and cadavers. Experimental results provided the initial/final elastic modulus for each specimen and assessed the non-linear and time-dependent behaviour of the tissue. The different foot regions were investigated, and the main differences were observed when comparing the elastic moduli, especially the final elastic ones. It resulted in a higher level for the medial region (89 ± 77 MPa) compared to the others (from 51 ± 29 MPa for the heel pad to 11 ± 7 for the metatarsal). Finally, results have been used to define a visco-hyperelastic constitutive model, whose hyperelastic component, which describes tissue non-linear behaviour, was described using an Ogden formulation. The identified and validated tissue constitutive parameters could serve, in the early future, for the computational model of the healthy foot.

It is a common experience, reported by patients who have undergone manual therapy that uses deep friction, to perceive soreness in treatment areas; however, it is still not clear what causes it and if it is therapeutically useful or a simple side effect. The purpose of this narrative review is to determine whether manual and physical therapies can catalyze an inflammatory process driven by HA fragments. The literature supports the hypothesis that mechanical stress can depolymerize into small pieces at low molecular weight and have a high inflammatory capacity. Many of these pieces are then further degraded into small oligosaccharides. Recently, it has been demonstrated that oligosaccharides are able to stop this inflammatory process. These data support the hypothesis that manual therapy that uses deep friction could metabolize self-aggregated HA chains responsible for increasing loose connective tissue viscosity, catalyzing a local HA fragment cascade that will generate soreness but, at the same time, facilitate the reconstitution of the physiological loose connective tissue properties. This information can help to explain the meaning of the inflammatory process as well as the requirement for it for the long-lasting resolution of these alterations.

Abstract Background Cornea is a composite tissue exhibiting nonlinear and time-dependent mechanical properties. Corneal ulcers are one of the main pathologies that affect this tissue, disrupting its structural integrity and leading to impaired functions. In this study, uniaxial tensile and stress-relaxation tests are developed to evaluate stress-strain and time-dependent mechanical behaviour of porcine corneas. Results The samples are split in two groups: some corneas are analysed in an unaltered state (healthy samples), while others are injured with alkaline solution to create an experimental ulcer (lesioned samples). Furthermore, within each group, corneas are examined in two conditions: few hours after the enucleation (fresh samples) or after 7 days in a specific culture medium for the tissue (cultured samples). Finally, another condition is added: corneas from all the groups undergo or not a cross-linking treatment. In both stress-strain and stress-relaxation tests, a weakening of the tissue is observed due to the imposed conditions (lesion, culture and treatment), represented by a lower stiffness and increased stress-relaxation. Conclusions Alkali-induced corneal stromal melting determines changes in the mechanical response that can be related to a damage at microstructural level. The results of the present study represent the basis for the investigation of traditional and innovative corneal therapies.

Biomechanical studies are expanding across a variety of fields, from biomedicine to biomedical engineering. From the molecular to the system level, mechanical stimuli are crucial regulators of the development of organs and tissues, their growth and related processes such as remodelling, regeneration or disease. When dealing with cell mechanics, various experimental techniques have been developed to analyse the passive response of cells; however, cell variability and the extraction process, complex experimental procedures and different models and assumptions may affect the resulting mechanical properties. For these purposes, this review was aimed at collecting the available literature focused on experimental chondrocyte and chondron biomechanics with direct connection to their biochemical functions and activities, in order to point out important information regarding the planning of an experimental test or a comparison with the available results. In particular, this review highlighted (i) the most common experimental techniques used, (ii) the results and models adopted by different authors, (iii) a critical perspective on features that could affect the results and finally (iv) the quantification of structural and mechanical changes due to a degenerative pathology such as osteoarthritis.

The biomechanical response of cortical and trabecular bone tissues represents a fundamental aspect for the interpretation of the functional response of dental implants. In the case of misfit, the interaction phenomena occurring within the surgical and the subsequent healing phases must be interpreted primarily in the light of the response of bone tissue. This is influenced by the specific loadings induced, characterized by intensity and variable trends. The pilot study reported, which intentionally refers to a simple case of a two-implants frame, is addressed to define the method to approach the biomechanical investigation of the problem and to attest the necessity to integrate clinical competences with biomechanical analysis for interpreting different aspects of osseointegration. The action induced in cortical and trabecular bone regions depending on the implant frame conformation, the surgical procedure adopted, the varying condition at the bone–implant interface and the evolutionary trend of healing are the principal aspects to be considered to evaluate the osseointegration process. The biomechanical reliability of the specific implant frame is investigated in terms of bone–implant interaction by means of numerical models. This approach can offer valid information and support clinical practice under the fundamental condition that bone biomechanical behavior is properly characterized and represented in the model, in spite of the complex formulation to be adopted.

The surgical treatment of urinary incontinence is often performed by adopting an Artificial Urinary Sphincter (AUS). AUS cuff represents a fundamental component of the device, providing the mechanical action addressed to urethral occlusion, which can be investigated by computational approach. In this work, AUS cuff is studied with reference to both materials and structure, to develop a finite element model. Materials behavior is investigated using physicochemical and mechanical characterization, leading to the formulation of a constitutive model. Materials analysis shows that AUS cuff is composed by a silicone blister joined with a PET fiber-reinforced layer. A nonlinear mechanical behavior is found, with a higher stiffness in the outer layer due to fiber-reinforcement. The cuff conformation is acquired by Computer Tomography (CT) both in deflated and inflated conditions, for an accurate definition of the geometrical characteristics. Based on these data, the numerical model of AUS cuff is defined. CT images of the inflated cuff are compared with results of numerical analysis of the inflation process, for model validation. A relative error below 2.5% was found. This study is the first step for the comprehension of AUS mechanical behavior and allows the development of computational tools for the analysis of lumen occlusion process. The proposed approach could be adapted to further fluid-filled cuffs of artificial sphincters.

Human Fascia Lata (FL) is a connective tissue with a multilayered organization also known as aponeurotic fascia. FL biomechanics is influenced by its composite structure formed by fibrous layers (usually two) separated by loose connective tissue. In each layer, most of the collagen fibers run parallel in a distinct direction (with an interlayer angle that usually ranges from 75–80°), mirroring the fascia’s ability to adapt and withstand specific tensile loads. Although FL is a key structure in several musculoskeletal dysfunctions and in tissue engineering, literature still lacks the evidence that proves tissue anisotropy according to predominant collagen fiber directions. For this purpose, this work aims to analyze the biomechanical properties of ex-vivo FL (collected from fresh-frozen human donors) by performing uniaxial tensile tests in order to highlight any differences with respect to loading directions. The experimental outcomes showed a strong anisotropic behavior in accordance with principal collagen fibers directions, which characterize the composite structure. These findings have been implemented to propose a first constitutive model able to mimic the intra- and interlayer interactions. Both approaches could potentially support surgeons in daily practices (such as graft preparation and placement), engineers during in silico simulation, and physiotherapists during musculoskeletal rehabilitation, to customize a medical intervention based on each specific patient and clinical condition.

By leveraging the recent development of artificial intelligence algorithms, several medical sectors have benefited from using automatic segmentation tools from bioimaging to segment anatomical structures. Segmentation of the musculoskeletal system is key for studying alterations in anatomical tissue and supporting medical interventions. The clinical use of such tools requires an understanding of the proper method for interpreting data and evaluating their performance. The current systematic review aims to present the common bottlenecks for musculoskeletal structures analysis (e.g., small sample size, data inhomogeneity) and the related strategies utilized by different authors. A search was performed using the PUBMED database with the following keywords: deep learning, musculoskeletal system, segmentation. A total of 140 articles published up until February 2022 were obtained and analyzed according to the PRISMA framework in terms of anatomical structures, bioimaging techniques, pre/post-processing operations, training/validation/testing subset creation, network architecture, loss functions, performance indicators and so on. Several common trends emerged from this survey; however, the different methods need to be compared and discussed based on each specific case study (anatomical region, medical imaging acquisition setting, study population, etc.). These findings can be used to guide clinicians (as end users) to better understand the potential benefits and limitations of these tools.

Hollow organs are visceral organs that are hollow tubes or pouches (such as the intestine or the stomach, respectively) or that include a cavity (such as the heart) and which subserve a vital function [...]

Several studies have investigated cartilage degeneration and inflammatory subchondral bone and synovial membrane changes using magnetic resonance (MR) in osteoarthritis (OA) patients. Conversely, there is a paucity of data exploring the role of knee ligaments, infrapatellar fat pad (IFP), and suprapatellar fat pad (SFP) in knee OA compared to post-traumatic cohorts of patients. Therefore, the aim of this study was to analyze the volumetric and morphometric characteristics of the following joint tissues: IFP (volume, surface, depth, femoral and tibial arch lengths), SFP (volume, surface, oblique, antero–posterior, and cranio–caudal lengths), anterior (ACL) and posterior cruciate ligament (PCL) (volume, surface, and length), and patellar ligament (PL) (volume, surface, arc, depth, and length). Eighty-nine MR images were collected in the following three groups: (a) 32 patients with meniscal tears, (b) 29 patients with ACL rupture (ACLR), and (c) 28 patients affected by end-stage OA. Volume, surface, and length of both ACL and PCL were determined in groups a and c. A statistical decrease of IFP volume, surface, depth, femoral and tibial arch lengths was found in end-stage OA compared to patients with meniscal tear (p = 0.002, p = 0.008, p < 0.0001, p = 0.028 and p < 0.001, respectively) and patients with ACLR (p < 0.0001, p < 0.0001, p = 0.008 and p = 0.011, respectively). An increment of volume and surface SFP was observed in group b compared to both groups a and c, while no differences were found in oblique, antero–posterior, and cranio–caudal lengths of SFP among the groups. No statistical differences were highlighted comparing volume, surface, arc, and length of PL between the groups, while PL depth was observed to be decreased in end-OA patients compared with meniscal tear patients (p = 0.023). No statistical differences were observed comparing ACL and PCL lengths between patients undergoing meniscectomy and TKR. Our study confirms that IFP MR morphometric characteristics are different between controls and OA, supporting an important role of IFP in OA pathology and progression in accordance with previously published studies. In addition, PL depth changes seem to be associated with OA pathology. Multivariate analysis confirmed that OA patients had a smaller IFP compared to patients with meniscal tears, confirming its involvement in OA.

The infrapatellar fat pad (IFP) is actively involved in knee osteoarthritis (OA). However, a proper description of which developmental modifications occur in the IFP along with age and in absence of joint pathological conditions, is required to adequately describe its actual contribution in OA pathophysiology. Here, two IFP sources were compared: (a) IFP from healthy young patients undergoing anterior-cruciate ligament (ACL) reconstruction for ACL rupture (n = 24); (b) IFP from elderly cadaver donors (n = 23). After histopathological score assignment to confirm the absence of inflammatory features (i.e., inflammatory infiltrate and increased vascularity), the adipocytes morphology was determined; moreover, extracellular matrix proteins were studied through histology and Second Harmonic Generation approach, to determine collagens content and orientation by Fast Fourier Transform and OrientationJ. The two groups were matched for body mass index. No inflammatory signs were observed, while higher area, perimeter, and equivalent diameter and volume were detected for the adipocytes in the elderly group. Collagen III displayed higher values in the young group and a lower total collagen deposition with aging was identified. However, collagen I/III ratio and the global architecture of the samples were not affected. A higher content in elastic fibers was observed around the adipocytes for the ACL-IFPs and in the septa cadaver donor-IFPs, respectively. Age affects the characteristics of the IFP tissue also in absence of a pathological condition. Variable mechanical stimulation, depending on age-related different mobility, could be speculated to exert a role in tissue remodeling.

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.

Osteoarthritis (OA) is one of the most common joint disorders. Evidence suggests that the infrapatellar fat pad (IFP) is directly involved in OA pathology. However, a comparison between OA versus non-OA IFP is still missing. Thus, the aim of this study was to compare IFP molecular, adipocytes and extracellular matrix characteristics of patients affected by OA, and patients undergoing anterior cruciate ligament (ACL) reconstruction. We hypothesized that not only inflammation but also changes in adipocytes and extracellular matrix (ECM) composition might be involved in OA pathogenesis. Fifty-three patients were enrolled. IFP biopsies were obtained, evaluating: (a) lymphocytic infiltration and vascularization; (b) adipocytes area and number; (c) adipo-cytokines and extracellular matrix gene expression levels; (d) IL-6 and VEGF protein production; (e) collagen fibers distribution. OA IFP was more inflamed and vascularized compared to ACL IFP. OA IFP adipocytes were larger and numerically lower (1.3-fold) than ACL IFP adipocytes. An increase of gene expression of typical white adipose tissue genes was observed in OA compared to ACL IFP. Collagen-types distribution was different in the OA IFP group compared to controls, possibly explaining the change of the biomechanical characteristics found in OA IFP. Statistical linear models revealed that the adipocyte area correlated with BMI in the OA group. In conclusion, inflammation and fibrotic changes of OA IFP could represent novel therapeutic targets to counteract OA.

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.