Characterisation of human penile tissue properties using experimental testing combined with multi-target inverse finite element modelling.

This paper presents an inverse finite element (FE) approach aimed at estimating multi-layered human penile tissues. The inverse FE approach integrates experimental force-displacement and boundary deformation data of penile tissues with a developed FE model and uses new experimental data on human penile tissue. The experimental study encompasses whole organ plate-compression tests and individual layer tensile and compression tests, providing comprehensive insights into the tissue's mechanical behaviour. The biomechanical characterisation of penile tissue is of crucial significance for understanding its mechanical behaviour under various physiological and pathological conditions. The FE model is constructed using the realistic geometry of the penile segment and appropriate constitutive models for each tissue layer to leverage the accuracy and consistency of the model. Through systematic variation of tissue parameters in the inverse FE algorithm, simulations achieve the best match with both force-displacement and deformed boundary results obtained from the whole organ plate-compression tests. Test results from individual tissue layers are also utilised to assess the estimated parameters. The proposed inverse FE approach allows for the estimation of penile tissue parameters with high precision and reliability, shedding light on the mechanical properties of this complex biological organ. This work has applications not only in urology but also for researchers in various disciplines of biomechanics. As a result, our study contributes to advancing the understanding of human penile tissue mechanics whilst the methodology could also be applied to a range of other soft biological tissues. STATEMENT OF SIGNIFICANCE: This research uses a multi-target inverse finite element (FE) approach for estimating the material parameters of human penile tissues. By integrating experimental data and a realistic FE model, this study achieves high-precision constitutive model parameter estimation, offering key insights into penile tissue mechanics under various loading conditions. The significance of this work lies in the use of this inverse FE approach for fresh-frozen human penile tissues, to identify the mechanical properties and constitutive models for both segregated tunica albuginea and corpus cavernosum as well as intact penile tissue segments. The study's scientific impact lies in its advancement of the understanding of human urological tissue mechanics, impacting researchers and clinicians alike.

Experimental testing combined with inverse-FE for mechanical characterisation of penile tissues.

Erectile dysfunction (ED) predominantly affects men in their 40-70s and can lead to poor quality of life. One option for ED treatment is surgical implantation of an inflatable penile prosthesis (IPP). However, they can be associated with negative outcomes including infection, migration or fibrosis. To improve outcomes, the interaction between the IPP device and surrounding tissues needs further investigation and this could be achieved using pre-clinical testbeds, but they need to be informed by extensive tissue testing. In this study, an experimental approach is adopted to characterise the mechanics of horse penile tissue and establish a testing protocol for penile tissue. The whole penis segments were tested in plate compression tests to obtain whole penis behaviour which is necessary for validation of a pre-clinical testbed, whilst tensile and compression tests were performed on individual penile tissues, namely corpus cavernosa and tunica albuginea. The second part of the paper deals with the development of a computational model employing an inverse finite element approach to estimate the material parameters of each tissue layer. These material parameters are in good agreement with the experimental results obtained from the individual tissue layers and whole organ tissue tests. This paper presents the first study proposing realistic nonlinear elastic material parameters for penile tissues and offers a validated testbed for IPPs. STATEMENT OF SIGNIFICANCE: Erectile Dysfunction (ED) affects over half the male population aged 40-70 potentially leading to poor quality of life. Patients not responding to conventional treatments of ED, are advised to use penile prostheses which can create an erection using implanted inflatable cylinders. A significant drawback of such prostheses, however, is the substantial tissue damage they can induce during their usage. Preclinical testbeds, including computational and bench-top models, could offer an efficient means of improving device designs to mitigate this damage but such testbeds require extensive knowledge of penile tissue properties. In this study, the authors determine penile tissue mechanics and apply an inverse FE approach to characterise the penile material properties required to validate preclinical models of the penis.

Dense Dilated Multi-Scale Supervised Attention-Guided Network for histopathology image segmentation.

Over the last couple of decades, the introduction and proliferation of whole-slide scanners led to increasing interest in the research of digital pathology. Although manual analysis of histopathological images is still the gold standard, the process is often tedious and time consuming. Furthermore, manual analysis also suffers from intra- and interobserver variability. Separating structures or grading morphological changes can be difficult due to architectural variability of these images. Deep learning techniques have shown great potential in histopathology image segmentation that drastically reduces the time needed for downstream tasks of analysis and providing accurate diagnosis. However, few algorithms have clinical implementations. In this paper, we propose a new deep learning model Dense Dilated Multiscale Supervised Attention-Guided (D2MSA) Network for histopathology image segmentation that makes use of deep supervision coupled with a hierarchical system of novel attention mechanisms. The proposed model surpasses state-of-the-art performance while using similar computational resources. The performance of the model has been evaluated for the tasks of gland segmentation and nuclei instance segmentation, both of which are clinically relevant tasks to assess the state and progress of malignancy. Here, we have used histopathology image datasets for three different types of cancer. We have also performed extensive ablation tests and hyperparameter tuning to ensure the validity and reproducibility of the model performance. The proposed model is available at www.github.com/shirshabose/D2MSA-Net.

The role of tissue biomechanics in the implantation and performance of inflatable penile prostheses: current state of the art and future perspective.

INTRODUCTION: Erectile dysfunction (ED) affects to some degree approximately 52% of the male population aged 40-70 years. Many men do not respond to, or are precluded from using, pharmaceutical treatments for ED and are therefore advised to consider penile prostheses. Different types of penile prosthesis are available, such as inflatable penile prostheses (IPPs). IPPs consist of a pair of inflatable cylinders inserted into the corpora cavernosa (CC). During inflation/deflation of these cylinders, the CC and other surrounding tissues such as the tunica albuginea (TA) are highly impacted. Therefore, it is critical to understand the mechanics of penile tissues for successful implantation of IPPs and to reduce tissue damage induced by IPPs. OBJECTIVES: We explored the importance of the biomechanics of penile tissues for successful IPP function and reviewed and summarized the most significant studies on penile biomechanics that have been reported to date. METHODS: We performed an extensive literature review of publications on penile biomechanics and IPP implantation. RESULTS: Indenters have been used to characterize the mechanical behavior of whole penile tissue; however, this technique applied only local deformation, which limited insights into individual tissue components. Although one reported study addressed the mechanical behavior of TA, this investigation did not consider anisotropy, and there is a notable absence of biomechanical studies on CC and CS. This lack of understanding of penile tissue biomechanics has resulted in computational models that use linear-elastic materials, despite soft tissues generally exhibiting hyperelastic behavior. Furthermore, available benchtop/synthetic models do not have tissue properties matched to those of the human penis, limiting the scope of these models for use as preclinical testbeds for IPP testing. CONCLUSION: Improved understanding of penile tissue biomechanics would assist the development of realistic benchtop/synthetic and computational models enabling the long-term performance of IPPs to be better assessed.

Exploring the Mechanical Properties and Performance of Type-I Collagen at Various Length Scales: A Progress Report.

Collagen is the basic protein of animal tissues and has a complex hierarchical structure. It plays a crucial role in maintaining the mechanical and structural stability of biological tissues. Over the years, it has become a material of interest in the biomedical industries thanks to its excellent biocompatibility and biodegradability and low antigenicity. Despite its significance, the mechanical properties and performance of pure collagen have been never reviewed. In this work, the emphasis is on the mechanics of collagen at different hierarchical levels and its long-term mechanical performance. In addition, the effect of hydration, important for various applications, was considered throughout the study because of its dramatic influence on the mechanics of collagen. Furthermore, the discrepancies in reports of the mechanical properties of collagenous tissues (basically composed of 20-30% collagen fibres) and those of pure collagen are discussed.

Fracture behaviour and toughening mechanisms of dry and wet collagen.

The growing interest to the use of collagen films for biomedical applications motivates the analysis of their fracture behaviour in different environments. Studies revealed the decreased mechanical strength and stiffness as well as increased plasticity in water compared to collagen specimens tested in air. However, the fracture behaviour of pure collagen films in both air and water has not been reported so far. In this paper, the entire process of mode-I loading of single-edge notched tension (SENT) specimens was recorded and analysed. In case of in-air (dry) specimens, cracks propagated rapidly in a brittle fashion while large plastic deformations were observed in aqua prior to failure due to crack opening and a blunting mechanism in wet specimens. The fracture-toughness parameters for pure collagen in air and in aqua were estimated using linear-elastic (KI and GI) and elasto-plastic (JI) fracture-mechanics approaches, respectively, following the force-displacement response and deformational behaviour. GIC and JI were 1365 ± 112 J/m2 and 2500 ± 440 J/m2, respectively. Scanning electron microscopy was used to observe the structural changes linked to collagen fibrils in the crack-tip area and the fracture surface. For in-air specimens, the former mostly exhibited extrinsic toughening (usually at micro scale) acting behind the crack-tip, while in-aqua intrinsic toughening acting ahead of a crack tip was found. Fractography of in-air specimens showed no occurrence of voids while multiple micro-voids were found for in-aqua specimens. STATEMENT OF SIGNIFICANCE: The fracture toughness and crack propagation of both mineralised (bone, dentine) and non-mineralised (skin) tissues has been extensively investigated over the past decades. Though these tissues are rich in collagen, the fracture properties of pure collagen have not been quantified yet at macroscale. Considering the applications of collagen films in tissue regeneration, it is essential to perform investigations of their fracture behaviour in both dry and wet conditions. Determining the effect of environment on the fracture behaviour of collagen and understanding its toughening mechanism are essential for prevention of failures during application. Moreover, this would give an insight for fabrication of tougher collagen-based biomaterials for biomedical uses.

Dense Dilated Deep Multiscale Supervised U-Network for biomedical image segmentation.

Biomedical image segmentation is essential for computerized medical image analysis. Deep learning algorithms allow us to design state-of-the-art models for solving segmentation problems. The U-Net and its variants have provided positive results across various datasets. However, the existing networks have the same receptive field at each level and the models are supervised only at the shallow level. Considering these two ideas, we have proposed the D3MSU-Net where the field of view in each level is varied depending upon the depth of the resolution layer and the model is supervised at each resolution level. We have evaluated our network in eight benchmark datasets such as Electron Microscopy, Lung segmentation, Montgomery Chest X-ray, Covid-Radiopaedia, Wound, Medetec, Brain MRI, and Covid-19 lung CT dataset. Additionally, we have provided the performance for various ablations. The experimental results show the superiority of the proposed network. The proposed D3MSU-Net and ablation models are available at www.github.com/shirshabose/D3MSUNET.

Dry vs. wet: Properties and performance of collagen films. Part II. Cyclic and time-dependent behaviours.

Collagen constitutes one-third of human-body proteins, providing mechanical strength and structural stability. Films of collagen are widely used in tissue engineering as scaffolds for wound healing and corneal implants, among other applications, presupposing the investigation of their mechanical properties and performance under various loading and environmental conditions. Part I of this research (Bose et al., 2020) demonstrated a drastic change in the mechanical response of collagen films under in-aqua conditions when compared to dry specimens. It was also observed that collagen films exhibited a strain-rate-dependent hardening behaviour with a strain-rate-sensitivity exponent ranging from 0.02 to 0.2. In Part II, the cyclic and time-dependent behaviours of collagen films were analysed under different loading and environmental conditions. Strain ratchetting was observed for collagen subjected to cyclic loading under various stress levels and environmental (in-air and in-aqua) conditions, while the in-aqua samples demonstrated an increase in the stiffness (50% in the first cycle), which may be referred to as cyclic stiffening. In contrast, the dry samples showed a drop in the modulus after the first cycle, without any subsequent changes. Additionally, time-dependent viscoelastic properties were analysed, using dynamic mechanical analysis as well as creep and stress-relaxation techniques. Tan Î´ values for dry samples ranged from 0.05 to 0.075, while for hydrated ones it varied from 0.12 to 0.24. Collagen films exhibited primary and secondary creep stages, while the initial stress-relaxation was fast followed by a monotonous decay. The stress-strain-time data obtained from experiments were fitted in Prony series to estimate the relaxation moduli and times.

Dry vs. wet: Properties and performance of collagen films. Part I. Mechanical behaviour and strain-rate effect.

Collagen forms one-third of the body proteome and has emerged as an important biomaterial for tissue engineering and wound healing. Collagen films are used in tissue regeneration, wound treatment, dural substitute etc. as well as in flexible electronics. Thus, the mechanical behaviour of collagen should be studied under different environmental conditions and strain rates relevant for potential applications. This study's aim is to assess the mechanical behaviour of collagen films under different environmental conditions (hydration, submersion and physiological temperature (37 °C)) and strain rates. The combination of all three environment factors (hydration, submersion and physiological temperature (37 °C)) resulted in a drop of tensile strength of the collagen film by some 90% compared to that of dry samples, while the strain at failure increased to about 145%. For the first time, collagen films were subjected to different strain rates ranging from quasi-static (0.0001 s-1) to intermediate (0.001 s-1, 0.01 s-1) to dynamic (0.1 s-1, 1 s-1) conditions, with the strain-rate-sensitivity exponent (m) reported. It was found that collagen exhibited a strain-rate-sensitive hardening behaviour with increasing strain rate. The exponent m ranged from 0.02-0.2, with a tendency to approach zero at intermediate strain rate (0.01 s-1), indicating that collagen may be strain-rate insensitive in this regime. From the identification of hyperelastic parameter of collagen film, it was found that the Ogden Model provides realistic results for future simulations.