Search Results (237)

Shear stress is a significant consideration in 3D bioprinting systems, with implications for cell viability and behaviour. This study hypothesised that relevant levels of shear stress would be generated during the process of 3D bioprinting human nasoseptal chondrocytes in a nanocellulose alginate bioink, with implications for cell viability and chondrogenic gene expression. Through a combined approach of in silico modelling and in vitro testing, we assessed chondrocyte viability and gene expression immediately within the first 72 h post-printing. Cell viability was determined using live–dead, alamarBlue and lactate dehydrogenase assays immediately and 24 h post-printing compared to cell-only and unprinted cell–biomaterial controls. Gene expression analysis of Type 2 collagen, SOX9, aggrecan and alkaline phosphatase gene expression was performed 4 h and 72 h post-printing. Computational fluid dynamics predicted a shear stress of 292 Pa and maximum fluid velocity of 19 mm/s during the bioprinting process. No statistically significant cell death or cell lysis was detected between groups immediately post-printing; however, statistically significant chondrocyte cell death was observed at 24 h in the printed group (p = 0.047). Moreover, the bioprinting process evoked a transient initial rise in both chondrogenic (SOX9, aggrecan) and osteogenic gene expression (ALP) with a marked suppression in type 2 collagen expression at 72 h (0.05, p = 0.0005), indicating biological effects evoked by shear stress during printing. This study highlights the importance of optimising the bioprinting process to facilitate low shear stress conditions for durable cartilage tissue engineering. Full article

Non-motor symptoms of PD impair quality of life and remain challenging to treat. Here, we examined the effects of short- (38 days) and long-term (178 days) supplementation with the natural polyamine spermidine on anhedonia and anxiety-like behaviours in a 6-hydroxydopamine-induced rat model of PD and linked them with spermidine’s anti-inflammatory properties. Behavioural assessments (cylinder, sucrose preference, elevated plus-maze tests) were conducted during progressive neurodegeneration and after oral treatment. Under the same conditions, peripheral inflammation was evaluated by the total leukocytes and their subpopulation numbers (hematological analysis) and by CD4⁺ and CD8⁺ T lymphocyte percentages (imaging flow cytometry); the plasma levels of interleukins 4 and 10 and corticosterone (enzyme-linked immunosorbent assay) were also evaluated. The safety of long-term supplementation was assessed using standard biochemical markers (chemistry analyser). Both treatment regimens reversed 6-hydroxydopamine-induced lymphopenia. Long-term spermidine treatment increased the number of TCD4⁺ lymphocytes and monocytes and elevated the plasma concentrations of IL-4 and IL-10, while reducing corticosterone levels. These immunomodulatory effects were associated with reduced anhedonia and anxiety. All of the biochemical safety parameters remained within normal ranges. Spermidine alleviates neuropsychiatric symptoms in a rat model of progressive neurodegeneration in the nigrostriatal system through its regulatory influence on peripheral immune responses. Exploring the systemic mechanisms underlying spermidine’s effects could unveil innovative supplementation strategies and expand treatment options for managing symptoms in PD. Full article

This review evaluates the emerging role of circulating tumour cells (CTCs) as clinically meaningful, minimally invasive biomarkers for oral squamous cell carcinoma (OSCC). Despite advances in management, OSCC continues to demonstrate high morbidity and mortality, largely due to late diagnosis and the absence of validated biomarkers for early detection or real-time monitoring. Conventional diagnostic tools, tissue biopsy, and imaging provide only static snapshots and fail to capture tumour heterogeneity or evolving biological behaviour. CTCs offer a novel and significant opportunity to address these limitations. Key findings from recent studies highlight that CTC enumeration correlates with tumour burden, nodal metastasis, recurrence, and overall prognosis. Molecular and phenotypic characterisation further reveals dynamic traits such as epithelial–mesenchymal transition, stemness, and therapy resistance, providing insights into metastatic potential and treatment failure. Technological advances, including immunocytochemistry, microfluidic capture platforms, PCR-based assays, and next-generation sequencing, have enhanced the sensitivity and specificity of CTC detection and enabled detailed multi-omic profiling. Collectively, evidence suggests that integrating CTC analysis into OSCC clinical workflows could improve early detection, refine risk stratification, personalise therapeutic strategies, and support longitudinal monitoring of disease dynamics. As research progresses, CTC-based diagnostics represent a promising frontier in shifting OSCC management toward more precise, adaptive, and biologically informed care. Full article

Neuropeptides regulate diverse physiological and behavioural processes in parasites, yet their functional roles in the infective larval stages of Schistosoma mansoni remain poorly defined. In this study, we identified miracidia-derived putative neuropeptides and examined their roles in regulating miracidial behaviour. Peptidomic analysis revealed ten putative neuropeptides, including five whose proteomic identification in this life stage was previously unreported. Neuropeptide precursor proteins were evaluated for stage-specific expression and Schistosoma genus specificity to prioritise candidates with potential functional and biocontrol relevance. Protein–protein interaction analysis identified Smp_176700 as a highly connected neuropeptide precursor associated with proteins implicated in miracidial structure and infection. Eight putative neuropeptides derived from six precursor proteins were synthesised and externally applied to miracidia in acute (1 min) and prolonged (360 min) behavioural assays. During acute exposure, most peptides induced significant concentration-dependent behavioural changes at 3 mg/mL and 0.1 mg/mL, characterised by reduced swimming velocity and increased directional change, with no significant effects at 0.01 mg/mL. Prolonged exposure revealed peptide-specific effects, with ASLSYF-OH and FLLGLPPSLRQH-OH producing the most pronounced behavioural modulation. These findings demonstrate that S. mansoni miracidia express bioactive neuropeptides capable of modulating larval behaviour, providing insight into schistosome neurobiology and identifying potential targets for transmission-blocking interventions. Full article

Endoperoxide-containing molecules based on the antimalarial drug artemisinin have demonstrated various biological properties, including modulation of calcium homeostasis. This study evaluated the toxicity and osteogenic activity of five newly developed tetraoxanes (YB1, YB9, YB11, YB17 and T2), alongside three of their non-peroxidic analogues (IC22, IC26 and IC33), in zebrafish (Danio rerio) larvae. For each compound, LC₅₀ values were first determined. Behavioural responses and morphological alterations were studied as indicators of toxicological impact. The osteogenic activity was assessed through the operculum assay, followed by the analysis of gene expression markers related to calcium homeostasis (atp2a1), oxidative stress (sod1, cat), and osteogenesis (sp7, oc2). All the compounds evaluated induced an inhibition of osteogenic activity. T2, YB11, IC33 and IC26 affected the locomotor function by decreasing swimming activity. IC26 and IC33 induced morphological toxicity, characterized by a curved trunk and alterations in larval body curvature. From all the compounds studied, YB1, YB9, YB17 and IC22 showed selective anti-osteogenic activity, without displaying significant behavioural or morphological toxicity. In conclusion, the presence of a peroxide bond in the molecular structure of the compounds increases the anti-osteogenic activity at lower concentrations. All evaluated compounds exhibited anti-osteogenic activity and can be regarded as anti-osteogenic agents. However, YB17 did not induce transcription alterations in the genes analyzed and may thus represent the most promising compound in conditions where a controlled inhibition of bone formation is desirable. Full article

Chronic diabetic wounds are challenging to treat due to persistent inflammation, oxidative stress, impaired angiogenesis, and dysregulated matrix remodelling. Hydrogen sulphide (H₂S) has emerged as a therapeutic mediator with antioxidant, anti-inflammatory, and pro-angiogenic properties; however, its clinical translation is limited by volatility and a short biological half-life. Controlled delivery systems, such as hydrogels, are therefore required to harness its potential. This study aimed to develop and evaluate a sodium 2-acrylamido-2-methylpropane sulfonate (Na-AMPS)-based adhesive hydrogel incorporating AP39, a mitochondria-targeted H₂S donor, for sustained localised delivery and promotion of wound healing. Hydrogel formulations were characterised for rheological behaviour, adhesion, swelling, and AP39 release. Cytocompatibility was assessed in human umbilical vein endothelial cells (HUVECs); human dermal fibroblasts, adult (HDFa); and keratinocytes. Anti-inflammatory, antioxidant, and matrix-modulatory effects were evaluated via interleukin-6 and 8 (IL-6/IL-8) secretion, reactive oxygen species (ROS) levels, mitochondrial membrane potential, matrix metalloproteinase-9 (MMP-9), and transforming growth factor-beta (TGF-β). Functional wound healing activity was assessed using tube formation and scratch assays in endothelial cells. AP39-loaded hydrogels exhibited predominantly elastic, shear-thinning behaviour, strong adhesion, rapid hydration, and sustained release of AP39 (11.63 ± 1.20% over 24 h). Across all cell types, 500 nM concentrations of AP39 were well tolerated. In diabetic-like stress conditions, AP39 significantly decreased ROS in HUVECs (50122 ± 5999 to 33,087 ± 1865 AU; p < 0.0001) and HDFa cells (41,367 ± 4225 to 29,813 ± 2406 AU; p < 0.0001). AP39 improved mitochondrial membrane potential in both cell types (p < 0.01–0.001) and decreased pro-inflammatory cytokines. IL-6 decreased in HUVECs (96.05 ± 4.22 pg/mL to 60.99 ± 4.21 pg/mL; p < 0.0001) and HDFa cells (77.54 ± 8.94 pg/mL to 52.25 ± 6.78 pg/mL; p < 0.001), whilst in HDFa cells, MMP-9 was reduced (419.4 ± 25.51 pg/mL to 174 ± 15.1 pg/mL; p < 0.0001). Finally, wound closure was enhanced in HUVECs. The AP39-loaded Na-AMPS hydrogel represents a multifunctional wound dressing capable of controlled H₂S delivery, mechanical stability, and biological activity to support tissue repair in diabetic wound environments. These results highlight this gel’s therapeutic potential for diabetic wound treatment. Full article

Background: Fibrotic remodelling of the lamina cribrosa (LC) is a defining pathological feature of glaucomatous optic neuropathy and contributes to progressive optic nerve head deformation and axonal vulnerability. LC cells from glaucomatous donors exhibit a myofibroblast-like phenotype characterised by excessive extracellular matrix (ECM) production, a process associated with chronic cellular stress. cAMP responsive element-binding protein 3-like 1 (CREB3L1) is an endoplasmic reticulum–resident transcription factor implicated in stress-responsive regulation of collagen synthesis and matrix homeostasis. The role of CREB3L1 in glaucomatous LC cells, however, remains poorly defined. Methods: Primary human LC cells derived from donors with confirmed glaucoma (GLC; n = 3) and age-matched non-glaucomatous controls (NLC; n = 3) were examined. CREB3L1 expression was assessed at the mRNA and protein levels using quantitative RT-PCR and Western immunoblotting. The functional effects of CREB3L1 suppression were evaluated using siRNA-mediated knockdown in GLC cells, followed by analysis of ECM gene transcription (α-smooth muscle actin, collagen type I alpha 1, fibronectin) and cellular metabolic activity using an MTS assay. Results: CREB3L1 mRNA and protein expression were significantly elevated in GLC cells compared with NLC cells. siRNA-mediated knockdown of CREB3L1 effectively reduced its expression in GLC cells and was associated with significant suppression of profibrotic ECM gene transcription. In addition, CREB3L1 knockdown resulted in a marked reduction in cellular metabolic activity in glaucomatous LC cells. Conclusions: These findings identify CREB3L1 as a regulator of ECM-associated gene expression and cellular behaviour in glaucomatous lamina cribrosa cells. While preliminary, the data suggest that CREB3L1 may contribute to pathological fibrotic remodelling at the optic nerve head. Further mechanistic and in vivo studies will be required to determine whether modulation of CREB3L1-mediated pathways represents a viable therapeutic strategy in glaucoma. Full article

Background/Objectives: Hydrogels infused with silver nanoparticles (AgNPs) are widely used for their antibacterial properties, yet their stability, specifically upon contact with solid growth media (agar), remains poorly explored. This study compared two hydrogel matrices, anionic Carbopol 934 and non-ionic Pluronic F127, incorporating AgNPs of three different sizes. The evaluation focused on colloidal stability and antibacterial efficacy against Gram-positive and Gram-negative bacteria. Methods: In this study AgNPs (~20, ~55, and ~65 nm) were synthesised via a wet-chemical method and characterised by UV–visible spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). AgNPs were incorporated into Carbopol 934 and Pluronic F127 hydrogel matrices. Colloidal stability was monitored over four months of storage and upon contact with tryptic soy agar (TSA). Antibacterial activity was assessed using agar diffusion assays. Results: Showed that both hydrogel systems maintained AgNP stability during storage, comparable to aqueous suspensions. However, upon contact with TSA, aggregation of Carbopol–AgNP hydrogels occurred, whereas Pluronic–AgNP hydrogels remained stable. In antibacterial assays, both hydrogels produced larger zones of inhibition (ZOI) than AgNP suspensions against Gram-negative bacteria (E. coli, P. aeruginosa), with Carbopol–AgNP hydrogels demonstrating superior efficacy in an inverse size-dependent manner. Against Gram-positive bacteria (S. aureus, S. epidermidis), Pluronic–AgNP hydrogels initially showed larger ZOIs due to the polymer’s intrinsic antibacterial activity. However, after correcting for this baseline, Carbopol–AgNP hydrogels exhibited superior net efficacy, with S. epidermidis showing greater susceptibility than S. aureus. Conclusions: While both Carbopol 934 and Pluronic F127 stabilise AgNPs during storage, the matrix type significantly influences behaviour at the biological interface. Carbopol–AgNP hydrogels aggregate upon contact with solid agar yet deliver superior, size-dependent antibacterial activity compared to the stable but less potent Pluronic systems. Full article

Studies conducted in first-episode psychosis (FEP) patients have shown alterations in inflammation and metabolism. Our objective was to investigate potential treatment-related effects on these systems in Italian FEP patients undergoing either an experimental treatment consisting of a multi-element psychosocial intervention (EXP), including cognitive–behavioural therapy, or treatment as usual (TAU). A total of 191 FEP patients with first contact between April 2010 and March 2011 were clinically assessed at baseline and after 9 months of treatment, and the serum levels of 19 analytes were determined through single or multiplex enzyme-linked immunosorbent assays (ELISAs). A significant increase was observed in leptin levels and a significant decrease in Glucagon-Like Peptide-1 (GLP-1) levels during the treatment (time effect, p < 0.001 for both), with no significant interaction between time and treatment type. Although ghrelin levels changed significantly over time in the whole cohort (p = 0.008), a significant decrease was observed only in the EXP group (post hoc test: p = 0.001). None of the biomarkers measured at baseline showed a predictive effect on treatment efficacy, and no significant associations were identified between changes in clinical scores and changes in biomarker levels. These results suggest that early-phase psychosis treatments are associated with possible effects on metabolic regulation. Full article

During recent decades, bone cancer-related diseases have remained hard to treat because of poor diagnosis, systemic toxicity, and restricted conventional treatments. Hence, the fabrication of functionalised nanoparticles offers a promising alternative by limiting side effects and improving therapeutic outcomes. In this study, zinc-substituted hydroxyapatite (Zn-HA) nanoparticles were fabricated from biogenic tuna fish bone waste via a thermal decomposition method and subsequently functionalised with Catharanthus roseus (CR) flower extract to synthesise a Zn-HA/CR nanocomposite. Structural and compositional characterisations verified Zn ions incorporation into the HA lattice and efficient CR-derived phytochemical functionalisation without altering the hexagonal HA phase. Compared to pure hydroxyapatite, the Zn-HA/CR nanocomposite exhibited improved surface morphology, enhanced swelling behaviour and degradation, and increased microhardness. The nanocomposite demonstrated significantly enhanced antibacterial activity against Staphylococcus aureus and Escherichia coli. The Zn-HA/CR nanocomposite also showed strong, dose-dependent antioxidant activity in DPPH assays. Furthermore, in vitro cytotoxicity studies using MG-63 (HOS) osteosarcoma cancer cells revealed that the proposed nanocomposite leads to pronounced morphological alterations and reduced cell viability. The prepared Zn-HA/CR nanocomposite would be a potential nanocomposite for enhanced antioxidant and anticancer activity, which highlights this composite as a multifunctional biomaterial platform for therapeutic applications. Full article

Dysregulation of the deubiquitinating enzyme Ubiquitin-specific peptidase 14 (USP14) is implicated in several neurodegenerative diseases, and IU1, an allosteric inhibitor, has shown neuroprotective effects by reducing protein aggregate toxicity. This study aimed to develop new IU1 analogues and evaluate their ability to mitigate amyloid-β (Aβ) accumulation and toxicity in Alzheimer’s disease (AD) cell and Caenorhabditis elegans worm models. IU1 and 71 newly designed analogues identified using the AtomNet^® virtual screening platform were assessed in an amyloid precursor protein-C terminal fragment/amyloid-β (APP-C99/Aβ)-producing AD cell model using a high-throughput toxicity assay. Lead compounds were further evaluated for their effects on neurodegeneration, behaviour, and survival. IU1 reduced Aβ-mediated toxicity and neurodegeneration in cell and worm models. Of the 71 analogues predicted to bind ubiquitin-specific peptidase 14 (USP14), two compounds, AA10 and AA51, showed >50% rescue of Aβ-induced toxicity and robust enhancement of autophagy and proteasome activity. In Caenorhabditis elegans, both compounds alleviated glutamatergic neuron loss and rescued behavioural impairments. IU1 and analogues exhibit protective effects against Aβ toxicity in AD models. Analogues AA10 and AA51 showed greater potency than IU1 and effectively enhanced proteostasis pathways. These findings support USP14 as a promising therapeutic target and provide a basis for the development of improved IU1-derived compounds for AD and related disorders. Full article

Precise quantification of fine motor behaviour is essential for understanding neural circuit function and for evaluating therapeutic interventions in neurological disorders. While markerless pose estimation frameworks such as DeepLabCut (DLC) have transformed behavioural phenotyping, the choice of convolutional neural network (CNN) backbone has a critical impact on tracking performance, particularly in tasks involving small distal joints and frequent occlusions. In this study, we present the first systematic comparison of nine CNN architectures implemented in DLC for lateral-view analysis of skilled reaching movements in the Montoya Staircase test, a gold-standard assay for forelimb dexterity in rodent models of stroke and neurodegenerative disease. Using a dataset comprising both control and primary motor cortex (M1)–lesioned mice, we evaluated model performance across six key dimensions: spatial accuracy (RMSE, PCK@5 px), mean average precision (mAP), robustness to occlusions, inference speed, and GPU memory usage. Our results demonstrate that multi-scale DLCRNet architectures substantially outperform conventional backbones. DLCRNet_ms5 achieved the highest overall accuracy, while DLCRNet_stride16_ms5 provided the most favourable balance between precision and computational efficiency. These findings provide practical methodological guidance for neuroscience laboratories and highlight the importance of CNN architecture selection for the reliable quantification of fine motor behaviour in preclinical research. Full article

Background: It is well known that host factors are capable of regulating microbial behaviours such as growth, metabolic pathways, virulence properties, and antimicrobial susceptibilities. In this respect, the present study aimed to investigate the relationship between insulin and various virulence properties of Pseudomonas aeruginosa ATCC 27853. Methods: Growth alterations, biofilm formation, motility, haemolytic activity, and pigment production (pyocyanin and pyoverdine) were determined in the presence/absence of three different insulin concentrations (10 µU/mL –20 µU/mL –200 µU/mL) under in vitro conditions. In addition, changes in bacterial virulence were evaluated in an in vivo animal (Caenorhabditis elegans) model. Alterations in growth, haemolytic activity, and pigment production were investigated spectrophotometrically. Biofilm formation was examined using the crystal violet well-plate assay. A soft agar plate method was used to detect swimming motility. Results: According to the results, all three insulin concentrations enhanced the bacterial growth. On the other hand, biofilm production, swimming motility, and haemolytic activity decreased in the presence of all insulin concentrations. Pyocyanin production was shown to be increased in the presence of only 10 µU/mL of insulin, but pyoverdine production did not change. In vivo animal survival rates showed that 200 µU/mL of insulin decreased bacterial virulence. Conclusions: This research demonstrates that P. aeruginosa can sense and respond to mammalian hormones (insulin), which can modulate microbial virulence through diverse mechanisms, providing new insights that may be relevant to infection dynamics. Full article

Background/Objectives: Dental caries is one of the most prevalent chronic diseases in childhood. Rotary bur handpiece excavation has been the standardised mechanical benchmark for infected dentine removal in the primary dentition, but it is associated with noise, vibration, and nociceptive triggers that influence behavioural cooperation in paediatric patients. CMCR gels have been developed for selective softening and excavation of infected primary dentine without macroscopic removal of adjacent sound tissue at the protocol-defined site. The objective of this review was to systematically synthesise the evidence on chemomechanical caries removal (CMCR) using Papacarie or Brix 3000 compared with infected dentine excavation using rotary bur handpiece instrumentation in the primary (deciduous) dentition, focusing on excavation effectiveness, paediatric procedural tolerance, anaesthetic requirement, dentine surface morphology at the excavation interface, and protocol-level operative duration per primary molar. Methods: A systematic search was performed in PubMed, Web of Science, and Scopus for English-language studies from database inception to 31 December 2023. Although no eligible paediatric dental records addressing CMCR gels for excavation of infected primary dentine were identified before 2009, the earlier literature was not intentionally excluded; rather, it did not retrieve topic-specific matches meeting the eligibility criteria. Clinical and in vitro investigations evaluating CMCR gels (Papacarie or Brix 3000) for excavation of infected primary dentine in primary molars were eligible. Outcomes were aggregated qualitatively by excavation approach and reported per primary molar at the individual study protocol level. Quantitative pooling or meta-analysis was not conducted due to heterogeneity in study designs and lack of unified denominators across the included literature. Results: Fifteen studies were included (randomised clinical trials, observational clinical investigations, clinical comparative studies, and in vitro assessments) evaluating infected dentine excavation in primary molars. CMCR gels achieved successful excavation of infected primary dentine with dentine preservation at the adjacent non-infected interface without macroscopic loss of sound tissue. Individual study protocols that reported paediatric pain outcomes during primary-molar excavation registered lower pain scores, reduced acoustic/vibratory stress, lower anaesthetic escalation cycles, and decreased local anaesthesia requirement per primary molar compared with rotary bur handpiece excavation arms. Dentine surfaces analysed under SEM protocols at the infected excavation interface described patent tubules, absence of compacted smear at the interface, preserved intertubular dentine, and no iatrogenic gouging or macrofracture of non-infected primary dentine per molar at the individual study level. Operative duration for CMCR ranged from 10 to 25 min per primary molar per tooth, while rotary bur handpiece excavation required 3–10 min per primary molar per tooth, depending on cavity extension and dentine hardness, as defined by each study protocol. Microleakage and bond-strength assays performed in vitro at the individual protocol level did not register disadvantage signals traceable to adhesive or sealing incompatibility following CMCR gel excavation per primary molar. Conclusions: CMCR with Papacarie or Brix 3000 enables protocol-level selective excavation of infected primary dentine in primary molars, reducing acoustic, vibratory, and nociceptive triggers that influence behaviour and local anaesthetic requirement per primary molar. Clinical inference should be restricted to infected dentine excavation per primary-molar denominators, avoiding extrapolation to all caries depths or all deciduous-tooth types. Standardised paediatric primary-molar infected dentine excavation trials with homogeneous denominators, bias-controlled outcome instruments, and longitudinal follow-up are required to strengthen cavity-depth indications, pulp-proximal excavation reliability, and restorative longevity guidance in the primary dentition clinical workflow. Full article

The development of photocurable hydrogel biomaterial inks with suitable rheology, low cytotoxicity, and tuneable mechanical properties is essential for reliable biofabrication. This study aimed to formulate PEGDA–gelatine–collagen inks using lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP) as photoinitiator. Rheological characterisation and flow-model fitting were performed, mechanical stiffness modulation under different light intensities was evaluated, complex structures were printed using direct extrusion and FRESH methodologies, and PEGDA/LAP extractables were quantified by NMR after controlled washing procedures. In vitro assays assessed cell viability and proliferation on the resulting scaffolds. The Herschel–Bulkley model best described the flow behaviour across formulations; while viscoelastic measurements showed that increasing light intensity progressively enhanced hydrogel stiffness, enabling fine control over final mechanical properties. NMR analysis showed that washing removed a substantial fraction of residual LAP, in agreement with the biological findings: fibroblasts failed to survive on unwashed scaffolds but exhibited robust proliferation and recovered their characteristic elongated morphology on washed constructs. Among all inks, PeGeCol_10_2 provided the best combination of shear-thinning behaviour, structural integrity, low residual photoinitiator, and tuneable mechanics. Using this formulation, we successfully printed large anatomical models with high fidelity and excellent handling properties, underscoring its potential for soft-tissue prosthetics and broader tissue-engineering applications. Full article