Tissue Mechanical Properties Research Articles

The role of the interfaces and cross-links on the mechanical behavior of mineralized collagen fibrils. A numerical approach

Mechanical properties of bone tissue are highly dependent on its hierarchical structure. The presence of microcracks and diffuse damage in lamellar bone is correlated with the failure of the collagen-mineral interface in mineralized collagen fibrils (MCF). The main goal of this work is to evaluate the mechanical behavior of the interfaces and quantify the stiffness loss of the MCF associated with different failure mechanisms, under controlled in-plane displacement. Additionally, we aim to study the role of the cross-links on the fibril mechanical response, beyond the interface failure. Inter- and intra-microfibrilar cross-links are analyzed. In order to address the first issue, a detailed representative volume of the MCF is analyzed by means of the finite element method, under the assumption of plane strain and periodic boundary conditions. In this model the interfaces between constituents are modeled with an exponential cohesive law. Enzymatic cross-links, located at the molecular terminals connecting each 4D (D=67nm) staggered molecules, are represented by non-linear springs. Three in-plane controlled deformations are applied. The results of this work provide the anisotropic stiffness loss of the tissue involved in the different failure mechanisms at the nano-scale length. The initiation of microcracks and the presence of damage zones are compatible with the failure mechanisms observed at interfaces. Interface failure entails a progressive stiffness loss, bringing a non-linear behavior of bone. The strength obtained for the longitudinal maximum deformation is more than 20 times the transverse strength and 3.5 times the shear strength. The quantification of the reduction percentage in the elastic moduli and the shear stiffness when the fibril is damaged, has a potential application in improving failure criteria based on degradation of elastic constants. When longitudinal elongation is applied, the mechanical contribution of the cross-links in delaying the failure initiation of the interface is shown. Likewise, results of this work confirm the scarce influence of the cross-links in the strain range analyzed. Additionally, a three-dimensional numerical model of several microfibrils is defined with the aim of analyzing the mechanical relevance of inter- and intra-microfibrilar cross-links, beyond the interface failure. Results confirm that cross-links transfer the load when strain increases, being highlighted the mechanical competence of the trivalent cross-links.

Integration of Sustainable and Net-Zero Concepts in Shape-Memory Polymer Composites to Enhance Environmental Performance.

This review research aims to enhance the sustainability and functionality of shape-memory polymer composites (SMPCs) by integrating advanced 4D printing technologies and sustainable manufacturing practices. The primary objectives are to reduce environmental impact, improve material efficiency, and expand the design capabilities of SMPCs. The methodology involved incorporating recycled materials, bio-based additives, and smart materials into 4D printing processes, and conducting a comprehensive environmental impact and performance metrics analysis. Significant findings include a 30% reduction in material waste, a 25% decrease in energy consumption during production, and a 20% improvement in shape-memory recovery with a margin of error of ±3%. Notably, the study highlights the potential use of these SMPCs as biomimetic structural biomaterials and scaffolds, particularly in tissue engineering and regenerative medicine. The ability of SMPCs to undergo shape transformations in response to external stimuli makes them ideal for creating dynamic scaffolds that mimic the mechanical properties of natural tissues. This increased design flexibility, enabled by 4D printing, opens new avenues for developing complex, adaptive structures that support cell growth and tissue regeneration. In conclusion, the research demonstrates the potential of combining sustainable practices with 4D printing to achieve significant environmental, performance, and biomedical advancements in SMPC manufacturing.

Systematic analysis of constitutive models of brain tissue materials based on compression tests

It's crucial to understand the biomechanical properties of brain tissue to comprehend the potential mechanisms of traumatic brain injury. This study, distinct from homogeneous models, integrates axonal coupling in both axial and transverse compressive experiments within a continuum mechanics framework to capture its intricate mechanical behaviors. Fresh porcine brains underwent unconfined compression at strain rates of 0.001/s and 0.1/s to 0.3 strain, allowing for a comprehensive statistical analysis of the directional, regional, and strain-rate-dependent mechanical properties of brain tissue. The established constitutive model, fitted to experimental data, delineates material parameters providing intuitive insights into the stiffness of gray/white matter isotropic matrices and neural fibers. Additionally, it predicts the mechanical performance of white matter matrix and axonal fibers under compressive loading. Results reveal that gray matter is insensitive to loading direction, exhibiting insignificant stiffness variations within regions. White matter, however, displays no significant differences in mechanical properties under axial and transverse loading, with an overall higher average stress than gray matter and a more pronounced strain-rate effect. Stress-strain curves indicate that, under axial compression, white matter axons primarily resist the load before transitioning to a matrix-dominated response. Under transverse loading, axonal fibers exhibit weaker resistance to lateral pressure. The mechanical behavior of brain tissue is highly dependent on loading rate, region, direction, and peak strain. This study, by combining experimentation with phenomenological modeling, elucidates certain phenomena, contributing valuable insights for the development of precise computational models.

A novel stress sensor enables accurate estimation of micro-scale tissue mechanics in quantitative micro-elastography.

Quantitative micro-elastography (QME) is a compression-based optical coherence elastography technique enabling the estimation of tissue mechanical properties on the micro-scale. QME utilizes a compliant layer as an optical stress sensor, placed between an imaging window and tissue, providing quantitative estimation of elasticity. However, the implementation of the layer is challenging and introduces unpredictable friction conditions at the contact boundaries, deteriorating the accuracy and reliability of elasticity estimation. This has largely limited the use of QME to ex vivo studies and is a barrier to clinical translation. In this work, we present a novel implementation by affixing the stress sensing layer to the imaging window and optimizing the layer thickness, enhancing the practical use of QME for in vivo applications by eliminating the requirement for manual placement of the layer, and significantly reducing variations in the friction conditions, leading to substantial improvement in the accuracy and repeatability of elasticity estimation. We performed a systematic validation of the integrated layer, demonstrating >30% improvement in sensitivity and the ability to provide mechanical contrast in a mechanically heterogeneous phantom. In addition, we demonstrate the ability to obtain accurate estimation of elasticity (<6% error compared to <14% achieved using existing QME) in homogeneous phantoms with mechanical properties ranging from 40 to 130 kPa. Furthermore, we show the integrated layer to be more robust, exhibiting increased temporal stability, as well as improved conformity to variations in sample surface topography, allowing for accurate estimation of elasticity over acquisition times 3× longer than current methods. Finally, when applied to ex vivo human breast tissue, we demonstrate the ability to distinguish between healthy and diseased tissue features, such as stroma and cancer, confirmed by co-registered histology, showcasing the potential for routine use in biomedical applications.

A dopamine-assisted antioxidative in situ-forming hydrogel with photothermal therapy for enhancing scarless burn wound healing

Burn wounds are characterized by complex physiological and pathophysiological response and the management of burn wounds is challenging. In situ-forming hydrogels and photothermal therapy (PTT) are promising treatments for wound healing. However, current research on biomaterials for burn treatment mainly focuses on either promoting healing or inhibiting scar formation, few studies have combined the two functions of one material. In this study, we prepared a multifunctional, in-situ cross-linked hydrogel termed CPOD hydrogel, which integrates carboxymethyl chitosan (CMCS), polyvinyl alcohol (PVA), oxidized hyaluronic acid (OHA), and dopamine (DA), coupled with photothermal therapy (PTT). In vitro experiments showed that the CPOD hydrogel had outstanding biocompatibility, suitable tissue adhesion and mechanical properties, excellent antimicrobial and antioxidant properties. This hydrogel showed PTT properties, which could produce mild heat in the early stage and higher temperatures in the later stage under NIR radiation. In the treatment of burn wounds of mice, application of CPOD hydrogel with PTT significantly promoted wound healing in the early stage and inhibited scar formation in the later stage, showing great potential for future innovation and application.

How well do 3D-printed tissue mimics represent the complex mechanics of biological soft tissues? An example study with Stratasys' cardiovascular TissueMatrix materials.

Tissue mimicking materials are designed to represent real tissue in applications such as medical device testing and surgical training. Thanks to progress in 3D-printing technology, tissue mimics can now be easily cast into arbitrary geometries and manufactured with adjustable material properties to mimic a wide variety of tissue types. However, it is unclear how well 3D-printable mimics represent real tissues and their mechanics. The objective of this work is to fill this knowledge gap using the Stratasys Digital Anatomy 3D-Printer as an example. To this end, we created mimics of biological tissues we previously tested in our laboratory: blood clots, myocardium, and tricuspid valve leaflets. We printed each tissue mimic to have the identical geometry to its biological counterpart and tested the samples using identical protocols. In our evaluation, we focused on the stiffness of the tissues and their fracture toughness in the case of blood clots. We found that the mechanical behavior of the tissue mimics often differed substantially from the biological tissues they aim to represent. Qualitatively, tissue mimics failed to replicate the traditional strain-stiffening behavior of soft tissues. Quantitatively, tissue mimics were stiffer than their biological counterparts, especially at small strains, in some cases by orders of magnitude. In those materials in which we tested toughness, we found that tissue mimicking materials were also much tougher than their biological counterparts. Thus, our work highlights limitations of at least one 3D-printing technology in its ability to mimic the mechanical properties of biological tissues. Therefore, care should be taken when using this technology, especially where tissue mimicking materials are expected to represent soft tissue properties quantitatively. Whether other technologies fare better remains to be seen.

Assessing tissue mechanical properties: Development of a custom-made tensile device and application on rodents sciatic nerves

The development of biomaterials such as synthetic scaffolds for peripheral nerve regeneration requires a precise knowledge of the mechanical properties of the nerve in physiological-like conditions. Mechanical properties (Young’s modulus, maximum stress and strain at break) for peripheral nerves are scarce and large discrepancies are observed in between reports. This is due in part to the absence of a robust testing device for nerves. To overcome this limitation, a custom-made tensile device (CMTD) has been built. To evaluate its reproducibility and accuracy, the imposed speed and distance over measured speed and distance was performed, followed by a validation using poly(dimethylsiloxane) (PDMS), a commercial polymer with established mechanical properties. Finally, the mechanical characterization of rodents (mice and rats) sciatic nerves using the CMTD was performed. Mouse and rat sciatic nerves Young’s modulus were 4.57 ± 2.04 and 19.2 ± 0.86 MPa respectively. Maximum stress was 1.26 ± 0.56 MPa for mice and 3.81 ± 1.84 MPa for rats. Strain at break was 53 ± 17% for mice and 32 ± 12% for rats. The number of axons per sciatic nerve was found to be twice higher for rats. Statistical analysis of the measured mechanical properties revealed no sex-related trends, for both mice and rats (except for mouse maximum stress with p=0.03). Histological evaluation of rat sciatic nerve corroborated these findings. By developing a robust CMTD to establish the key mechanical properties (Young’s modulus, maximum stress and strain at break) values for rodents sciatic nerves, our work represent an essential step toward the development of better synthetic scaffolds for peripheral nerve regeneration.

Biomimetic strategies for the deputization of proteoglycan functions.

Proteoglycans (PGs), which have glycosaminoglycan chains attached to their protein cores, are essential for maintaining the morphology and function of healthy body tissues. Extracellular PGs perform various functions, classified into the following four categories: i) the modulation of tissue mechanical properties; ii) the regulation and protection of the extracellular matrix; iii) protein sequestration; and iv) the regulation of cell signaling. The depletion of PGs may significantly impair tissue function, encompassing compromised mechanical characteristics and unregulated inflammatory responses. Since PGs play critical roles in the function of healthy tissues and their synthesis is complex, the development of PG mimetic molecules that recapitulate PG functions for tissue engineering and therapeutic applications has attracted the interest of researchers for more than 20years. These approaches have ranged from semisynthetic graft copolymers to recombinant PG domains produced by cells that have undergone genetic modifications. This review discusses some essential extracellular PG functions and approaches to mimicking these functions.

Development of a Multi-Material 3D Printer for Functional Anatomic Models.

Anatomic models are important in medical education and pre-operative planning as they help students or doctors prepare for real scenarios in a risk-free way. Several experimental anatomic models were made with additive manufacturing techniques to improve geometric, radiological, or mechanical realism. However, reproducing the mechanical behavior of soft tissues remains a challenge. To solve this problem, multi-material structuring of soft and hard materials was proposed in this study, and a three-dimensional (3D) printer was built to make such structuring possible. The printer relies on extrusion to deposit certain thermoplastic and silicone rubber materials. Various objects were successfully printed for testing the feasibility of geometric features such as thin walls, infill structuring, overhangs, and multi-material interfaces. Finally, a small medical image-based ribcage model was printed as a proof of concept for anatomic model printing. The features enabled by this printer offer a promising outlook on mimicking the mechanical properties of various soft tissues.

Phase-Domain Photoacoustic Mechanical Imaging for Quantitative Elastography and Viscography.

The role and importance of mechanical properties of cells and tissues in pathophysiological processes have widely been acknowledged. However, current elastography techniques most based on transverse elastic waves, diminish the translation of wave speed into elastic modulus due to its limited wave propagation direction. Here, we propose phase-domain photoacoustic mechanical imaging (PD-PAMI), leveraging the initial time and phase response characteristics of an omnidirectional photoacoustic elastic wave to quantitatively extract elastic and viscous moduli. Theoretical simulations and experiment on tissue-mimicking phantoms with different levels of viscoelastic properties were conducted to validate the approach with a precision in elasticity and viscosity estimation of 4.6% and 6.6%, respectively. The trans-scale viscoelasticity mappings over three length scales-covering cell, tissue section, and in vivo organ, were provided to demonstrate the scalability of the technique with different implementations of PD-PAMI. Experiments on animal models of breast tumour and atherosclerosis reveal that PD-PAMI technique enables effective monitoring of the viscoelastic parameters for examinations of the diseases involved with the variations in collagen or lipid composition and in inflammation level. PD-PAMI technique opens new perspectives of conventional PA imaging and provides new technical way for biomechanical imaging, prefiguring potential clinical applications in mechanopathology-involved disease diagnosis.

Anisotropy of microstructure features and tensile properties of Ti–48Al–2Cr–2Nb alloy produced by electron beam powder bed fusion

A Ti–48Al–2Cr–2Nb alloy was produced by electron beam powder bed fusion. The effect of the volume energy density parameter on the forming quality was investigated, and the tissue characteristics, hardness distribution, and mechanical properties of the alloy were analyzed. The results showed that the quality was better when the volume energy density parameter was 21.5–22.5 J/mm3. The microstructure of the alloy has the phenomenon of changing with the forming height: with an increase in the forming height, the forming part produces the phenomenon of strip microstructure along the construction direction, and the regional microstructure variability occurs under the cross section of the same height. The average hardness of the alloy reached 375.2 HV at the bottom, 381.8 HV in the middle, and 389.6 HV at the top, and the standard errors of the hardness values were 12.40, 10.49, and 7.12 HV, respectively, with the microhardness showing a gradual increase along the molding direction, and the homogeneity was gradually better. The transverse tensile strength at room temperature reached 526 MPa, the yield strength reached 461 MPa, and the elongation at break reached 1.24%, while the longitudinal tensile strength reached 486 MPa, the yield strength reached 414 MPa, and the elongation at break reached 1.02%.

The Relationship between Placental Shear Wave Elastography and Fetal Weight-A Prospective Study.

Background/Objectives: The utility of shear wave elastography (SWE) as an adjunct to ultrasound biometry and Doppler velocimetry for the examination of placental dysfunction and suboptimal fetal growth is unclear. To date, limited data exist correlating the mechanical properties of placentae with fetal growth. This study aimed to investigate the relationship between placental shear wave velocity (SWV) and ultrasound estimated fetal weight (EFW), and to ascertain if placental SWV is a suitable proxy measure of placental function in the surveillance of small-for-gestational-age (SGA) pregnancies. Methods: This prospective, observational cohort study compared the difference in placental SWV between SGA and appropriate-for-gestational-age (AGA) pregnancies. There were 221 women with singleton pregnancies in the study cohort-136 (61.5%) AGA and 85 (38.5%) SGA. Fetal biometry, Doppler velocimetry, the deepest vertical pocket of amniotic fluid, and mean SWV were measured at 2-4-weekly intervals from recruitment to birth. Results: There was no difference in mean placental SWV in SGA pregnancies compared to AGA pregnancies, nor was there any relationship to EFW. Conclusions: Although other studies have shown some correlation between increased placental stiffness and SGA pregnancies, our investigation did not support this. The mechanical properties of placental tissue in SGA pregnancies do not result in placental SWVs that are apparently different from those of AGA controls. As this study did not differentiate between constitutionally or pathologically small fetuses, further studies in growth-restricted cohorts would be of benefit.

Biomechanical Properties and Cellular Responses in Pulmonary Fibrosis.

Pulmonary fibrosis is a fatal lung disease affecting approximately 5 million people worldwide, with a 5-year survival rate of less than 50%. Currently, the only available treatments are palliative care and lung transplantation, as there is no curative drug for this condition. The disease involves the excessive synthesis of the extracellular matrix (ECM) due to alveolar epithelial cell damage, leading to scarring and stiffening of the lung tissue and ultimately causing respiratory failure. Although multiple factors contribute to the disease, the exact causes remain unclear. The mechanical properties of lung tissue, including elasticity, viscoelasticity, and surface tension, are not only affected by fibrosis but also contribute to its progression. This paper reviews the alteration in these mechanical properties as pulmonary fibrosis progresses and how cells in the lung, including alveolar epithelial cells, fibroblasts, and macrophages, respond to these changes, contributing to disease exacerbation. Furthermore, it highlights the importance of developing advanced in vitro models, based on hydrogels and 3D bioprinting, which can accurately replicate the mechanical and structural properties of fibrotic lungs and are conducive to studying the effects of mechanical stimuli on cellular responses. This review aims to summarize the current understanding of the interaction between the progression of pulmonary fibrosis and the alterations in mechanical properties, which could aid in the development of novel therapeutic strategies for the disease.

A Preliminary Study on Factors That Drive Patient Variability in Human Subcutaneous Adipose Tissues.

Adipose tissue is a dynamic regulatory organ that has profound effects on the overall health of patients. Unfortunately, inconsistencies in human adipose tissues are extensive and multifactorial, including large variability in cellular sizes, lipid content, inflammation, extracellular matrix components, mechanics, and cytokines secreted. Given the high human variability, and since much of what is known about adipose tissue is from animal models, we sought to establish correlations and patterns between biological, mechanical, and epidemiological properties of human adipose tissues. To do this, twenty-six independent variables were cataloged for twenty patients, which included patient demographics and factors that drive health, obesity, and fibrosis. A factorial analysis for mixed data (FAMD) was used to analyze patterns in the dataset (with BMI > 25), and a correlation matrix was used to identify interactions between quantitative variables. Vascular endothelial growth factor A (VEGFA) and actin alpha 2, smooth muscle (ACTA2) gene expression were the highest loadings in the first two dimensions of the FAMD. The number of adipocytes was also a key driver of patient-related differences, where a decrease in the density of adipocytes was associated with aging. Aging was also correlated with a decrease in overall lipid percentage of subcutaneous tissue, with lipid deposition being favored extracellularly, an increase in transforming growth factor-β1 (TGFβ1), and an increase in M1 macrophage polarization. An important finding was that self-identified race contributed to variance between patients in this study, where Black patients had significantly lower gene expression levels of TGFβ1 and ACTA2. This finding supports the urgent need to account for patient ancestry in biomedical research to develop better therapeutic strategies for all patients. Another important finding was that TGFβ induced factor homeobox 1 (TGIF1), an understudied signaling molecule, which is highly correlated with leptin signaling, was correlated with metabolic inflammation. Furthermore, this study draws attention to what we define as "extracellular lipid droplets", which were consistently found in collagen-rich regions of the obese adipose tissues evaluated here. Reduced levels of TGIF1 were correlated with higher numbers of extracellular lipid droplets and an inability to suppress fibrotic changes in adipose tissue. Finally, this study indicated that M1 and M2 macrophage markers were correlated with each other and leptin in patients with a BMI > 25. This finding supports growing evidence that macrophage polarization in obesity involves a complex, interconnecting network system rather than a full switch in activation patterns from M2 to M1 with increasing body mass. Overall, this study reinforces key findings in animal studies and identifies important areas for future research, where human and animal studies are divergent. Understanding key drivers of human patient variability is required to unravel the complex metabolic health of unique patients.

Pressurized membranes between walls: Thermodynamic process changes force and stiffness

Pressurized solids are ubiquitous in nature. Mechanical properties of biological tissues arise from cell turgor pressure and membrane elasticity. Flat contact between cells generate nonlinear forces. In this work, cells are idealized as pressurized elastic membranes in frictionless contact with one another. Contact forces are experimentally measured on rubber-like membranes and computed using finite element analysis (FEA). FEA matches experimental force-indentation relationships from small to large indentations. With the chosen dimensionless numbers, data gather on a master curve. The isobaric force exhibits a 4/3 power law over 1.5 decades of indentation. Forces for other thermodynamic processes (adiabatic, isothermal/osmotic and isochoric) are interpolated from isobaric data. Regarding stiffness, the isochoric process is superlinear contrary to the sublinear isobaric stiffness. Simple force-indentation relationships are given for each process.

MXene-Based Skin-Like Hydrogel Sensor and Machine Learning-Assisted Handwriting Recognition.

Conductive hydrogels are widely used in flexible sensors owing to their adjustable structure, good conductivity, and flexibility. The performance of excellent mechanical properties, high sensitivity, and elastic modulus compatible with human tissues is of great interest in the field of flexible sensors. In this paper, the functional groups of trisodium citrate dihydrate (SC) and MXene form multiple hydrogen bonds in the polymer network to prepare a hydrogel with mechanical properties (Young's modulus (23.5-92 kPa) of similar human tissue (0-100 kPa)), sensitivity (stretched GF is 4.41 and compressed S1 is 5.15 MPa-1), and durability (1000 cycles). The hydrogel is able to sensitively detect deformations caused by strain and stress and can be used in flexible sensors to detect human movement in real time such as fingers, wrists, and walking. In addition, the combination of matrix sensing and machine learning was successfully used for handwriting recognition with an accuracy of 0.9744. The combination of machine learning and flexible sensors shows great potential in areas such as healthcare, information security, and smart homes.

Highly stretchable dynamic hydrogels for soft multilayer electronics.

Recent progress in the development of synthetic polymer networks has enabled the next generation of hydrogel-based machines and devices. The ability to mimic the mechanical and electrical properties of human tissue gives great potential toward the fields of bioelectronics and soft robotics. However, fabricating hydrogel devices that display high ionic conductivity while maintaining high stretchability and softness remains unmet. Here, we synthesize supramolecular poly(ionic) networks, which display high stretchability (>1500%), compressibility (>90%), and rapid self-recovery (<30 s), while achieving ionic conductivities of up to 0.1 S cm -1. Dynamic cross-links give rise to inter-layer adhesion and a stable interface is formed on account of ultrahigh binding affinities (>1013 M-2). Superior adherence between layers enabled the fabrication of an intrinsically stretchable hydrogel power source, paving the way for the next generation of multi-layer tissue mimetic devices.

Ultrashort echo time magnetic resonance elastography for quantification of the mechanical properties of short T2 tissues via optimal control-based radiofrequency pulses.

The aim of the current study is to demonstrate the feasibility of radiofrequency (RF) pulses generated via an optimal control (OC) algorithm to perform magnetic resonance elastography (MRE) and quantify the mechanical properties of materials with very short transverse relaxation times (T2 < 5 ms) for the first time. OC theory applied to MRE provides RF pulses that bring isochromats from the equilibrium state to a fixed target state, which corresponds to the phase pattern of a conventional MRE acquisition. Such RF pulses applied with a constant gradient allow to simultaneously perform slice selection and motion encoding in the slice direction. Unlike conventional MRE, no additional motion-encoding gradients (MEGs) are needed, enabling shorter echo times. OC pulses were implemented both in turbo spin echo (OC rapid acquisition with refocused echoes [RARE]) and ultrashort echo time (OC UTE) sequences to compare their motion-encoding efficiency with the conventional MEG encoding (classical MEG MRE). MRE experiments were carried out on agar phantoms with very short T2 values and on an ex vivo bovine tendon. Magnitude images, wave field images, phase-to-noise ratio (PNR), and shear storage modulus maps were compared between OC RARE, OC UTE, and classical MEG MRE in samples with different T2 values. Shear storage modulus values of the agar phantoms were in agreement with values found in the literature, and that of the bovine tendon was corroborated with rheometry measurements. Only the OC sequences could encode motion in very short T2 samples, and only OC UTE sequences yielded magnitude images enabling proper visualization of short T2 samples and tissues. The OC UTE sequence produced the best PNRs, demonstrating its ability to perform anatomical and mechanical characterization. Its success warrants in vivo confirmation in further studies.

Basement membrane patterning by spatial deployment of a secretion-regulating protease.

While paradigms for patterning of cell fates in development are well-established, paradigms for patterning morphogenesis, particularly when organ shape is influenced by the extracellular matrix (ECM), are less so. Morphogenesis of the Drosophila egg chamber (follicle) depends on anterior-posterior distribution of basement membrane (BM) components such as Collagen IV (Col4), whose symmetric gradient creates tissue mechanical properties that specify the degree of elongation. Here we show that the gradient is not regulated by Col4 transcription but instead relies on post-transcriptional mechanisms. The metalloprotease ADAMTS-A, expressed in a gradient inverse to that of Col4, limits Col4 deposition in the follicle center and manipulation of its levels can cause either organ hyper- or hypo-elongation. We present evidence that ADAMTS-A acts within the secretory pathway, rather than extracellularly, to limit Col4 incorporation into the BM. High levels of ADAMTS-A in follicle termini are normally dispensable but suppress Col4 incorporation when transcription is elevated. Our data show how an organ can employ patterned expression of ECM proteases with intracellular as well as extracellular activity to specify BM properties that control shape.

Biomimetic and non-biomimetic approaches in dura substitutes: the influence of mechanical properties.

The dura mater, the furthest and strongest layer of the meninges, is crucial for protecting the brain and spinal cord. Its biomechanical behavior is vital, as any alterations can compromise biological functions. In recent decades, interest in the dura mater has increased due to the need for hermetic closure of dural defects prompting the development of several substitutes. Collagen-based dural substitutes are common commercial options, but they lack the complex biological and structural elements of the native dura mater, impacting regeneration and potentially causing complications like wound/postoperative infection and cerebrospinal fluid leakage. To face this issue, recent tissue engineering approaches focus on creating biomimetic dura mater substitutes. The objective of this review is to discuss whether mimicking the mechanical properties of native tissue or ensuring high biocompatibility and bioactivity is more critical in developing effective dural substitutes, or if both aspects should be systematically linked. After a brief description of the properties and architecture of the native cranial dura, we describe the advantages and limitations of biomimetic dura mater substitutes to better understand their relevance. In particular, we consider biomechanical properties' impact on dura repair's effectiveness. Finally, the obstacles and perspectives for developing the ideal dural substitute are explored.