Acta Biomaterialia

Pressure ulcers arise from sustained mechanical loading that impairs perfusion and damages skin tissues, yet the coupled mechanical and biological mechanisms of their formation and healing remain poorly characterized. We addressed this gap using a mouse model in which dorsal skin underwent 72 hours of magnet-induced ischemia followed by reperfusion, with tissue collected at 0, 3, 6, and 9 days and compared with baseline controls. From each mouse, we obtained paired samples from pressure ulcer and remote control (non-loaded) sites, mapped thickness by tissue profilometry, and performed equibiaxial testing with full-field digital image correlation and inverse finite element analysis to estimate regional material parameters. In parallel, we quantified CD31+ vasculature, F4/80+ macrophages, collagen content, and key cytokines. Pressure ulcer sites were compressed and thinner at Day 0, developed ulcers by Day 3, and continued to remodel through Day 9. Mechanical tests revealed heterogeneous strain fields with elevated deformation along ulcer borders, while remote control tissue deformed more homogeneously. These mechanical changes evolved alongside dynamic vessel and macrophage repopulation, increased collagen content at early time points, and cytokine upregulation within pressure ulcer tissue. Collectively, our data define the spatiotemporal co-evolution of tissue geometry, mechanics, collagen remodeling, and inflammation in pressure ulcers and provide a quantitative foundation for predictive mechanobiological models.

The foreign body response (FBR) is an immune mediated event that occurs with every material implant. The extent of the fibrosis is dependent on many factors including the biomaterial design, tissue location, and host factors such as age, sex, ancestry, diet. There are known clinical outcomes of implants dependent on age and sex, including increased fibrosis and implant failure in aged and female patients. As the population ages, there is a growing need to understand how aging affects the FBR, and how preclinical models can capture this to guide biomaterial design. Here, we investigated how chronic fibrosis in a murine model of the FBR is altered by two biological factors: age and sex. We investigated changes in fibrosis using a volumetric muscle loss (VML) injury model coupled with polycaprolactone (PCL) or polyethylene (PE) microparticle implants. Fibrosis was quantified through gene expression, microscopic analysis of histologic sections, and the corresponding immune response measured via gene expression and flow cytometry data. We found gene expression differences with immune pathways enriched in female mice, and microscopy revealed collagen birefringence area increased in young male mice. Both the innate and adaptive immune response were altered by age and sex via T cell and macrophage phenotype, and the effects of aging differed between sexes. These results reveal both variables contribute to discrepant outcomes in both fibrosis and the local immune response to synthetic material implants. This demonstrates a clear need to understand and account for the influence of biological factors in biomaterial design.

The ability to generate vascularized tissue constructs supplied by surgically accessible vessels remains a major limitation in reconstructive tissue engineering. Previous work demonstrated that positioning porous biomaterials around a vein can induce extensive vascular sprouting and generate a vascularized tissue volume without creation of an arteriovenous loop. However, this phenomenon has principally been demonstrated using rigid calcium-phosphate scaffolds, limiting its direct relevance to soft-tissue reconstruction. Here, we investigated whether a flexible decellularized dermal matrix could similarly be vascularized around a single unmodified vein and whether autologous dermal fibroblasts could further enhance this response. Decellularized rat dermis, with or without autologous dermal fibroblast seeding, was implanted either subcutaneously in the dorsal region or around the femoral vein for 8 weeks. Following Microfil perfusion, three-dimensional micro-CT demonstrated an extensive branching vascular network within perivenous constructs. Vessel volume relative to tissue volume was 0.2 +/- 0.1% in subcutaneous constructs without fibroblasts (n = 11) and 0.6 +/- 0.2% with fibroblasts (n = 9), compared with 6.+/- 1.4 % in perivenous constructs without fibroblasts (n = 10) and 7.3+/- 1.2% with fibroblasts (n = 10). Histology and immunohistochemistry similarly showed greater cellular repopulation and substantially higher CD31- and -SMA-positive vessel densities following perivenous implantation. Integrated two-way ANOVA of the same 8-week data confirmed a dominant effect of implantation site across the vascular outcomes, while fibroblast seeding significantly affected vascular volume, dermal remodeling, and nuclear density. The effect of fibroblast seeding on vascular volume was site dependent, with a significant implantation site fibroblast interaction. At 8 weeks, the vascularized dermal construct was completely dissected free from the surrounding tissues while maintaining its connection to the femoral vein. A small superficial incision into the isolated dermis produced visible bleeding, supporting an acute functional connection of the intradermal vascular network to the host circulation while the femoral venous connection was preserved. After flap elevation, perivenous constructs retained substantially greater vascular volume and showed more complete surface healing and organized skin architecture than subcutaneous constructs. Fibroblast seeding accelerated wound closure, while its effect on post-elevation vascular volume depended on implantation site: VV/TV decreased in subcutaneous constructs but increased in perivenous constructs. These findings show that single-vein vascularization can extend from rigid calcium-phosphate biomaterials to a compliant biological extracellular-matrix scaffold and may provide a simplified axial vascularization strategy without arterialization or incorporation of an arterial vessel.

The primary source of strength in ligaments and tendons are hierarchically organized collagen fibers. These fibers largely do not regenerate after injury, with repair, nor in engineered replacements, limiting treatment options. Previously, we developed a culture system which guides ACL fibroblasts in high-density collagen gels to form native-size hierarchical fibers over 6 weeks, and demonstrated that intermittent cyclic stretch further improves maturation. However, additional maturation is needed for clinical relevance. Interestingly, we found cyclic load affected cells differentially depending on the degree of organization, with 10% cyclic strain driving early improvements in unorganized gels and 5% strain being more beneficial later in culture once cells were on aligned fibers. Here, we explored whether a stepped cyclic load, that increased or decreased in strain magnitude as collagen fibers developed, further improved maturation. We hypothesized that progressively decreasing cyclic strain as organization increases would drive cells to produce more mature hierarchical fibers, resulting in stronger replacements. Controls had intermittent cyclic stretch at 0, 5, 7, or 10% strain throughout culture, while stepped load constructs were cyclically loaded with a strain that increased or decreased by 2-3% every 2 weeks as constructs matured. Contrary to our hypothesis, neither decreasing nor increasing load led to further tissue maturation. We hypothesize stepped cyclic load may disrupt cellular tensional homeostasis, leading to repeated remodeling of collagen and shifted proteoglycan accumulation. This study provides insight into how stepped cyclic loading affects hierarchical fiber formation and maturation, which will help to engineer stronger replacements and better rehabilitation protocols.

Three groups of touch-spun 3D scaffolds with uniform fiber diameters and varying interfiber spacing were studied to identify optimal conditions for NIH/3T3-GFP fibroblast growth. All scaffold groups exhibited higher cell viability relative to control levels after 14 days of culture, with the highest viability observed for scaffolds with a 50.61 {+/-} 15.35 m interfiber spacing. Although cell counts indicated comparable cell growth across groups, scaffolds with medium and large interfiber spacing demonstrated an improved capacity to sustain viable cells without necrotic core formation. These findings provide insight into the optimal structural design of touch-spun 3D scaffolds for tissue engineering applications.

Purpose: Fibrotic remodeling of the uterus, associated with aging, disease, and environmental exposures, alters collagen organization and tissue stiffness, yet how these changes influence organ-level mechanical behavior remains poorly understood. Glutaraldehyde (GA)-induced collagen crosslinking was used as a controlled surrogate for fibrotic remodeling to determine whether image-informed inverse finite element analysis (iFEA), combined with inflation testing and micro-computed tomography (microCT), could detect and quantify the resulting changes in uterine constitutive behavior. Methods: Murine uteri (n = 6 untreated, n = 6 GA-crosslinked) underwent volume-controlled balloon inflation with simultaneous microCT imaging to quantify deformation of the inner and outer wall boundaries for iFEA. Specimen-specific Gasser-Ogden-Holzapfel (GOH) finite element models were optimized by adjusting model parameters to reproduce experimentally measured wall contours throughout inflation. Model performance was evaluated using contour root mean square error (RMSE), and parameter identifiability was assessed through sensitivity analyses. Results: GA treatment significantly increased inflation work, linear stiffness, and maximum inflation resistance (p < 0.001). The iFEA framework accurately reproduced experimental deformation (RMSE < 3%) and revealed significant increases in the estimated GOH parameters C10 (9.2-fold), k1 (2.0-fold), and k2 (2.7-fold), consistent with increased effective tissue stiffness and a shift toward earlier collagen fiber recruitment. Sensitivity analyses demonstrated unique, well-defined minima for all parameter combinations. Conclusion: Image-informed iFEA provides a quantitative framework for relating collagen remodeling to organ-level uterine mechanics through specimen-specific constitutive parameter estimation. This approach establishes a foundation for investigating the mechanical consequences of uterine fibrosis and other remodeling processes.

A major challenge in vascular tissue engineering is the development of scalable fabrication methods capable of producing vascular grafts with suitable mechanical properties and hemocompatibility for both preclinical evaluation and future clinical translation. Using a recently developed method to generate acellular vascular grafts from densified collagen hydrogel, we present a proof-of-concept in vivo evaluation of the scalable collagen graft technology. Thick-walled, genipin-crosslinked grafts, representative of a fabrication approach applicable to clinically relevant vessel sizes, were implanted as interposition grafts in the rat abdominal aorta. These grafts supported rapid neointima formation and re-endothelialisation of the luminal surface but developed late thrombosis, highlighting the challenges of evaluating clinically scalable grafts in small-animal models. To enable assessment of the platform in millimetre-scale vessels, we developed a thin-walled (~100 {micro}m), non-crosslinked graft using a constrained densification approach and hyaluronic acid-mediated modulation of collagen fibril assembly to improve compliance matching and hemocompatibility, with the latter providing a matrix-level approach that may complement surface-bound antithrombotic coatings. These grafts remained patent for up to 17 weeks and exhibited neointima formation, re-endothelialisation, and early cellular infiltration into the graft wall. Together, these findings demonstrate in vivo functionality of densified collagen vascular grafts and establish a foundation for future evaluation in larger animal models.

Current treatment of orthopedic ligament injury relies principally on non-regenerative materials and surgical repair rather than strategies that promote intrinsic tissue regeneration. This study evaluated whether biologic augmentation with XWRAP, a human amniotic membrane allograft, combined with a cryopreserved amniotic-fluid-derived biologic containing micronized human amnion membrane, promotes regeneration of ligament architecture in a rabbit medial collateral ligament (MCL) gap-defect model. Standardized 4-mm mid-substance MCL gap defects were created in New Zealand White rabbits (n=3) and either treated with the amniotic membrane/amniotic-fluid biologic combination or left untreated, with intact contralateral or adjacent MCL serving as native controls; ligaments were evaluated by transmission electron microscopy at 2 and 6 weeks post-procedure, with collagen fibril diameter quantified from calibrated high-magnification micrographs. Treated defects developed significantly larger mean collagen fibril diameters than untreated defects at both time points (75 vs. 50 nm at 2 weeks and 88 vs. 62 nm at 6 weeks; p<0.0001 for each comparison), reaching approximately 90% of native, uninjured ligament fibril diameter (98 nm) by 6 weeks. Treated defects also developed a broader, bimodal fibril-diameter distribution resembling native ligament architecture, whereas untreated defects remained characterized by a narrow, unimodal population of small-diameter fibrils typical of scar-associated repair. These findings indicate that biologic augmentation with XWRAP combined with an amniotic-fluid-derived biologic promotes a regenerative, rather than purely reparative, healing response following ligament injury, progressively restoring collagen fibril architecture toward that of native tissue in this preclinical model.

Synthetic grafts remain ineffective for small-caliber vascular applications due to thrombosis and intimal hyperplasia. To address these limitations, our lab designed a multilayer graft consisting of a hydrogel coating that promotes post-implantation endothelialization and an electrospun mesh that matches arterial mechanical properties. Damage-resistant hydrogels were engineered using a double-network system composed of polyether urethane diacrylamide and N-acryloyl glycinamide to enhance fracture resistance through hydrogen bonding. In this study, we utilized redox initiation to apply conformal, durable hydrogels to electrospun grafts. Bioactivity wa introduced using streptococcal collagen-like proteins containing 1{beta}1 and 2{beta}1 integrin-binding motifs, enabling selective cell-material interactions that support endothelialization while preserving acute thromboresistance. To establish the feasibility of these grafts as off-the-shelf devices, we evaluated coating integrity and bioactivity retention following sterilization and dynamic physiological loading. Sterilized composites exhibited surgically-associated damage resistance, indicating that sterilization did not compromise hydrogel durability. Coating integrity and bioactivity were also preserved after six weeks of physiological loading. Acut thromboresistance was supported by both static platelet adhesion assays and dynamic whole-blood bioreactor studies using heparinized blood, with low platelet adhesion observed relative to ePTFE. Finally, a pilot ovine carotid model demonstrated successful surgical handling and sustained graft patency. Collectively, these results highlight the promise of multilayer vascular grafts as durable, thromboresistant conduits for small-diameter vascular applications. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=60 SRC="FIGDIR/small/741222v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@14ec910org.highwire.dtl.DTLVardef@17259e8org.highwire.dtl.DTLVardef@6cb611org.highwire.dtl.DTLVardef@1251d7d_HPS_FORMAT_FIGEXP M_FIG C_FIG

Despite lacking a dedicated structural function, brain tissue is exposed to severe mechanical loading during accidents and trauma, with potentially permanent or lethal consequences. Therefore, characterizing its mechanical behavior assumes particular importance for designing protective equipment, planning surgeries, and training neurosurgeons, tasks that often rely on physical brain replicas made from phantom materials. Although the mechanics of brain tissue has been extensively studied, the selection of suitable phantom materials still relies on simplified metrics that fail to capture the highly nonlinear and rate-dependent behavior of the brain. In this work, we characterize the mechanical response at low-to-medium strain rates of common synthetic brain phantom materials, including Sylgard 527, Ecoflex Gel, and a composite hydrogel, and establish rigorous comparisons with porcine brain tissue as a benchmark. To this end, we employ a multi-step stress relaxation protocol under both uniaxial extension and compression across two different strain rates, introduce thermodynamic metrics, and perform comparisons based on rigorous statistical analysis. In particular, we isolate the thermodynamic equilibrium stress-strain curves, representing the baseline material's response, from rate-dependent dissipative inelastic effects, relatable to viscoelastic and poroelastic mechanisms. Our results provide a thorough comparison, revealing critical limitations in existing simulant materials and highlighting significant space for developing improved brain surrogates. The comprehensive dataset collected can also support the calibration of constitutive models, enhancing the predictive accuracy of numerical simulations involving brain tissue and its surrogates. More broadly, this study highlights the need to move beyond simplistic, scalar-metric-based comparisons of mechanical responses across materials.

Osteochondral repair requires restoration of zonally organised articular cartilage and subchondral bone, yet translatable implants rarely reproduce this spatial complexity. Here, we developed an off-the-shelf, cell-free multilayer scaffold comprising a superficial 2% (w/v) articular cartilage extracellular matrix (AC-ECM) phase, an intermediate 5% AC-ECM phase and a basal 6% bone ECM (BN-ECM) phase. The scaffold formed continuous interfaces, displayed regionally distinct pore sizes and resisted permanent deformation during cyclic compression. In vitro, constructs seeded with caprine mesenchymal stromal and articular cartilage progenitor cells supported cell expansion and the accumulation of sulfated glycosaminoglycan- and collagen-rich matrix, with regional differences in collagen I, II and X deposition. Following eight weeks of subcutaneous implantation, cell-seeded scaffolds contained more collagenous matrix than unseeded controls, while vascularisation preferentially localised to the BN-ECM phase. The scaffold was then evaluated against empty defects in a caprine osteochondral model for six months. Scaffold treatment significantly improved macroscopic and histological repair, increased chondral tissue fill (~60% versus ~40%), limited cartilage-like tissue extension into the subchondral region and generated a more native-like superficial collagen organisation. Repair tissue further exhibited greater collagen II immunoreactivity, increased ACAN and COL2A1 expression and reduced COL1A2 expression relative to empty defects, although deeper bone repair was not significantly improved. These findings demonstrate that tissue-specific ECM layering can spatially guide endogenous repair and substantially improve cartilage restoration without exogenous cells or growth factors in a clinically relevant large-animal model, while identifying subchondral bone regeneration as the remaining design challenge for complete osteochondral repair.

Engineered living materials (ELMs) offer a promising route to biologically manufactured materials for healthcare, construction and manufacturing. However, their rational design is limited by the lack of quantitative relationships linking design parameters to material properties. Here, we show that a tabular foundation model (TabPFN), informed by a small library of living hydrogels, accurately predicts macroscopic material properties from genetic and process parameters. Models were evaluated for predicting storage modulus (G'), fibre content, thickness, and permeability of Escherichia coli-produced living hydrogels containing CsgA-based fibres fused to genetically encoded PEG-like biopolymers. On an independent validation set, TabPFN achieved the strongest prediction for G' (R2 = 85.1%), reducing RMSE by 48.0% compared to linear regression. Property-guided design further enabled identification of parameters for achieving living hydrogels with desired properties. These results establish a broadly applicable framework for predictive design of ELMs, reducing experimental screening and accelerating the discovery of materials with targeted properties.

Synthetic blood contacting devices frequently fail due to the lack of requisite biochemical and biomechanical cues needed to support transanastamotic endothelialization. During transanastomotic endothelialization, endothelial cells experience dynamic changes in extracellular mechanical cues as they migrate from compliant native vessels onto stiffer blood contacting device surfaces. However, how substrate stiffness and mechanical memory from prior mechanical environments influence temporal integrin remodeling and downstream endothelialization processes necessary to establish a stable endothelial layer remains poorly understood. In this study, human coronary artery endothelial cells (HCECs) were cultured on substrates spanning physiologically relevant stiffnesses to determine how substrate mechanics regulate collagen binding integrins and endothelialization. Increasing substrate stiffness promoted time dependent upregulation of 2{beta}1 integrin expression, whereas 1{beta}1 expression remained unchanged. Enhanced 2{beta}1 expression on stiff substrates was accompanied by increased vinculin associated focal adhesion maturation and accelerated endothelialization, characterized by increased proliferation, migration, and progression to confluence prior to reaching quiescence after 1 week. To better model transanastomotic migration and investigate mechanical history effects, cells initially expanded on compliant hydrogels were transferred to stiff substrates. Although these cells exhibited transient reductions in 2{beta}1 expression at early timepoints compared with tissue culture polystyrene expanded controls, no persistent differences in focal adhesion maturation, proliferation, migration, confluence, or quiescence were observed. Collectively, these findings demonstrate that substrate stiffness is a primary regulator of the early endothelialization processes required to establish a stable endothelial monolayer, whereas the influence of mechanical history is transient and ultimately superseded by the current mechanical environment. These findings also identify 2{beta}1 mediated mechanotransduction as a potential design target for blood contacting biomaterials that promote rapid endothelialization while supporting long-term endothelial cell quiescence.

Digital volume correlation (DVC) provides full-field three-dimensional measurements of internal deformation, but its accuracy and effective spatial resolution depend on image-processing and analysis choices. Here, we use fibrous, cartilaginous and mineralised tissues within a rat intervertebral disc (IVD) as a controlled multi-material case study, combining virtual compression with experimentally loaded synchrotron computed tomography images. We systematically evaluate phase retrieval and image filtering, bit-depth conversion, point-cloud design, subvolume size and strain-field smoothing. Stronger phase retrieval reduced correlation residuals while increasing displacement and strain errors, showing that residual minimisation alone can select poorer parameters. Image filtering sensitivity was greatest in fibrous tissue, which had the smallest characteristic image feature size, whereas inappropriate intensity mapping during 16-bit to 8-bit conversion preferentially degraded low-contrast cartilage. Increasing subvolume size, point spacing or strain-window size improved measurement robustness but progressively smoothed local strain heterogeneity. We demonstrate that the spatial resolution of strain measurement must be matched across tissue types in order to compare strain magnitude; in the IVD, matching DVC spatial resolution changed the apparent ratio of compressive strain among fibrous, cartilaginous and mineralised tissues from 3.1:1.9:1 to 14:7.7:1. These findings establish a sequential, deformation-based optimisation framework in which image characteristics guide processing, known deformations validate accuracy and strain fields are compared at matched measurement scales. The framework supports more reproducible and mechanically interpretable DVC analyses in heterogeneous biological and engineered materials.

Tympanic membrane perforations remain a common clinical problem, and although surgical intervention through tympanoplasty achieves high success rates, it is associated with donor-site morbidity, surgical complexity and limited restoration of the native radial and circumferential collagen architecture. In this study, 3D extrusion printing was utilized to create an active scaffold and attempt to promote collagen organization through shear-mediated structural alignment. An alginate-carboxymethyl cellulose (CMC) hydrogel with bovine SIS-dECM was prepared and investigated for its suitability as a bioink alternative to tympanoplasty grafts. The physiochemical, rheological and printability characteristics of the hydrogel were assessed. Successful decellularization was confirmed by histological analysis. The incorporation of the SIS-dECM into the hydrogel led to increased swelling, lower apparent viscosity, yield stress and flow stress while maintaining favourable printability and filament stability. Polarized optical microscopy was also used to study the influence of printing speed on the alignment of collagen to mimic the native tympanic membrane radial collagen architecture. Compared with the cast controls, the printed samples presented stronger birefringence signals. Biological evaluation demonstrated that the 15% dECM hydrogel exhibited the highest live cell area percentage and live/dead ratio after 48 h. In addition, the chick chorioallantoic membrane assay demonstrated that the dECM-containing hydrogels improved vascular density. The findings establish a printable, biologically active dECM bioink capable of generating bulk collagen organization through extrusion printing as a platform for tympanic membrane regeneration.

During tumor growth and progression, cancer cells are exposed to sustained physical confinement and volumetric compression that can alter cell volume, cytoskeletal organization, mechanotransduction, and invasive behavior. However, whether breast cancer cells retain a compression-induced mechanical memory after release from sustained volumetric compression, and how this memory influences subsequent migration and invasion, remains poorly understood. Here, by controlling cell volume using PEG - mediated volumetric compression, we investigated the compression and post-compression recovery responses of MCF-7 breast cancer cells. Cells were compressed for four days, followed by four days of recovery after PEG removal, and analyzed using daily morphological tracking, single-cell time-lapse imaging, F-actin and YAP staining, wound healing assays, and 3D spheroid invasion assays. We show that sustained volumetric compression shifts MCF-7 cells into a compact, jammed-like, low-motility state characterized by reduced morphodynamic remodeling, suppressed collective migration, and limited spheroid invasion. In contrast, post-compression recovery induces a distinct mechanobiological state marked by increased cell area and perimeter, altered single-cell trajectories, heterogeneous F-actin remodeling, enhanced YAP nuclear localization in enlarged recovered cells, accelerated wound closure, and increased spheroid invasion and cell dissemination. These findings suggest that prior volumetric compression can prime breast cancer cells for enhanced migration and invasion after stress release, supporting post-compression recovery as a form of mechanical memory that may contribute to tumor dissemination.

Introduction: The femoropopliteal artery undergoes substantial axial compression, bending, torsion, and pinching during limb flexion. When an implanted stent does not accommodate these deformations, repetitive biomechanical mismatch may alter the vascular response to implantation and contribute to restenosis. We tested whether designing a peripheral stent to better accommodate physiologic limb-flexion deformation reduces the subsequent inflammatory and neointimal response. Methods: A nitinol stent was developed using multi-objective computational optimization to maintain arterial apposition while reducing wall stress and luminal pinching during physiologic deformation. Sixteen Yucatan minipigs were studied in independent 3- and 6-month cohorts (n=8 each). Each animal received the optimized stent in one limb and a commercial stent with representative biomechanical behavior contralaterally. CTA quantified in vivo limb-flexion deformation, while CT and histology assessed stenosis, neointimal accumulation, inflammatory-cell burden, SMA-positive tissue, and extracellular-matrix composition. Results: The optimized stent accommodated greater axial shortening than the commercial comparator at both 3 months (11.2{+/-}2.7% vs. 6.6{+/-}2.1%, p=0.003) and 6 months (13.7{+/-}4.4% vs. 6.8{+/-}2.3%, p=0.004). Intimal hyperplasia volume was lower with the optimized stent at 3 months (227.5{+/-}85.2 vs. 350.0{+/-}130.5 mm3, p=0.002) and 6 months (183.6{+/-}46.2 vs. 261.2{+/-}60.6 mm3, p=0.001), with significantly lower maximum, mean, and median stenosis at both timepoints. At 3 months, macrophage and total inflammatory-cell counts were 51% and 45% lower, respectively, with the optimized stent. Histologic tissue area was 28% lower at 3 months and 12% lower at 6 months. SMA-positive tissue fraction was higher with the optimized stent at both timepoints, whereas elastin, glycosaminoglycan, and collagen fractions were similar between devices. Discussion: Improved accommodation of limb-flexion deformation was associated with a smaller inflammatory and neointimal response to stent implantation through 6 months, while overall neointimal matrix composition remained largely unchanged. These findings provide in vivo evidence that biomechanical compatibility with the dynamic lower-limb environment can influence vascular healing and should be considered a mechanistic design criterion for peripheral artery stents.

Background: Post-operative uterine adhesions remain a major clinical challenge, often leading to infertility and severe pelvic pain. Current anti-adhesion barriers lack the mechanical strength, tissue specificity, or bioactivity required for optimal regeneration of uterine tissue. To address these limitations, we developed a biomimetic, multilayer scaffold that replicates the structural and functional complexity of the myometrial and serosal layers of the uterus by combining a tunable polycaprolactone (PCL) mesh with a bioactive hydrogel derived from decellularized uterine extracellular matrix (dUECM) reinforced with sodium alginate (Alg). Materials and Methods: Composite scaffolds were fabricated using near-field melt electrowriting (MEW) to create precision-engineered PCL meshes with various infill angles (90{degrees}, 60{degrees}, 45{degrees}, and 30{degrees}), followed by impregnation with an alginate-dUECM hydrogel. A comprehensive physicochemical characterization was conducted using Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), and contact angle measurements. Mechanical properties were evaluated in both dry and wet states via uniaxial tensile testing. Swelling and degradation were assessed over 10 days. hTERT-HM cells were used for in vitro evaluation through Live/Dead staining, MTT, SEM, and immunocytochemistry for -SMA and DAPI. Results: The successful incorporation of the hydrogel into the PCL mesh was confirmed by the results obtained from FTIR and TGA analyses; these findings were further supported by contact angle studies, which showed a marked increase in hydrophilicity, resulting in a reduction of the static contact angle from 113 {+/-} 4{degrees} in the pure PCL to 60 {+/-} 12{degrees} in the hydrogel-infiltrated samples in the 30{degrees} group. Mechanical testing showed that the wet composite scaffolds maintained higher stiffness than hydrated native uterine tissue. Cell culture assays confirmed excellent cytocompatibility and proliferation, especially in 30 infill architecture. Immunofluorescence revealed strong -SMA expression and cytoskeletal organization, indicating phenotypic maturation of uterine smooth muscle cells for all groups. Conclusion: Among all groups, the 30 MEW mesh impregnated with Alg-dUECM hydrogel demonstrated the most balanced combination of mechanical resilience, degradation profile, wettability, and cellular compatibility. This structure most closely recapitulates the biological characteristics of uterine outer myometrium tissue, positioning it as a highly promising scaffold for regeneration and biofunctional anti-adhesion barrier applications.

The kidney is a critical soft-tissue organ responsible for blood filtration. Accurate constitutive models of the kidney are essential to predict tissue deformation and stress, yet existing models prescribe the strain energy function a priori, largely treat tissue variability as deterministic, and do not distinguish between cortex and medulla. Here we use Gaussian constitutive artificial neural networks to discover probabilistic strain energy functions for kidney cortex and medulla from tension, compression, and shear experiments. The medulla is approximately twice as stiff as the cortex across all three modes: The effective Young's moduli are 3.41, 5.04, and 4.48 kPa for the medulla and 1.43, 2.32, and 2.87 kPa for the cortex in tension, compression, and shear. Both regions display pronounced tension--compression asymmetry. When trained on all three modes, the network discovers strain energy functions in the second invariant alone over the tested deformation range. The cortex model selects two exponential I2 terms, while the medulla model selects an additional linear I2 term. Gaussian external weights propagate specimen-to-specimen variability into closed-form probabilistic stress predictions. Our region-specific probabilistic models capture the mechanical heterogeneity and variability of the kidney and enable more realistic simulations of kidney deformation and stress for surgical planning, needle interventions, and renal trauma.

Successful instrumented fusion of the lumbar spine is a complex surgical challenge, with positive patient outcomes dependent on careful surgical planning. Material selection is of critical importance to a mechanical construct supporting successful spinal fusion. Therefore, the aims of this study were to (a) evaluate the potential clinical use of finite element analysis (FEA) and (b) conduct a retrospective mechanical analysis of different implant materials in patients having undergone spinal fusion using FEA. Our methodology involved segmenting the spine from post-operative computed tomography (CT) image data from patients with previous spinal fusion. FEA models representing post-surgery cases were developed and different biomechanical loading conditions such as compression, flexion, bending and extension whilst testing pedicle screws of different materials were simulated. Patient specific finite element models were created, and biomechanical analysis were completed for all three patients. Polyetheretherketone (PEEK) constructs typically demonstrated lower peak implant stress when compared to titanium constructs for all spinal fusion levels. Furthermore, increasing the spinal fusion level resulted in significant differences in the maximum von Mises stress within both the bone and the instrumentation, whereas the 2-level fusion exhibited comparable stress levels in the bone irrespective of the instrumentation material. This pilot explores the potential of FEA as a clinical tool for assessing device and bone stresses. In our cohort, different materials can influence the stresses in both the instrumentation and the instrumented vertebrae, suggesting FEA can be useful pre- operative tool with regards to instrument selection and post-operatively to assess instrumentation and bone stresses. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=74 SRC="FIGDIR/small/742715v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@55959aorg.highwire.dtl.DTLVardef@d0b9d6org.highwire.dtl.DTLVardef@158c348org.highwire.dtl.DTLVardef@7ce828_HPS_FORMAT_FIGEXP M_FIG C_FIG