Critical-sized bone defects remain a major clinical challenge due to their limited self-healing capacity and the inability of current grafting materials to achieve both structural and mechanical integration. In this work, three-dimensional (3D) printed hydroxyapatite (HA) scaffolds with grid and honeycomb architectures and tunable infill densities (30-70%) were fabricated to investigate how architecture-controlled micromechanics influences bone regeneration. The scaffolds were evaluated in rat cranial (non-load-bearing) and tibial (load-bearing) defect models representing distinct mechanical environments. Micro-computed tomography (micro-CT), histological analyses, and high-speed nanoindentation (HSN) were used to quantify bone ingrowth, tissue distribution, and local stiffness. Grid scaffolds with 30% infill supported significantly greater bone volume fraction and more homogeneous regeneration, while HSN confirmed that the regenerated bone approached the modulus and hardness of native tissue. Comparable scaffold degradation and bone maturation were observed across both anatomical sites. These results show that scaffold architecture influences local nanomechanical properties and bone formation patterns, providing design principles for engineering reproducible, site-specific 3D-printed HA scaffolds. The findings further highlight that bioactive-free HA scaffolds can effectively support high-quality bone regeneration, offering a clinically translatable strategy for reconstructing critical-sized bone defects in orthopedic and craniofacial applications.

Stromal vascular fraction (SVF) from adipose tissue represents a promising source of regenerative cells. A major trend in SVF isolation is the increasing use of dedicated devices and systems to enhance standardization and reproducibility. Real-world implementation of new technologies requires consideration of workflow-related factors alongside biological results. This study primarily aimed to characterize the novel BMC Uniq® SVF device, describe a mechanical isolation approach (MI-SVF) with this device, and evaluate the cellular outcomes of MI-SVF. Enzymatic isolation (EI-SVF) was included as a reference method for comparison of selected cellular parameters. The BMC Uniq® SVF device is a spiral-based, closed system composed of two housings and three filters, designed as a sterile disposable unit. Lipoaspirate samples from 10 healthy female donors were equally divided and handled using MI-SVF (decantation, device processing, centrifugation) or EI-SVF (adding collagenase and post-digestion steps to the MI-SVF protocol). Total cell yield was significantly greater in the EI-SVF group (mean ± standard error (SE) 94.9 × 104 ± 6.4 × 104 versus 37.5 × 104 ± 2.7 × 104 for MI-SVF; p = 0.002). The flow cytometry demonstrated significantly higher relative proportions of CD90+ (10.3 ± 1.3

Additive manufacturing of silicone holds great promise in revolutionising the field of medicine and medical science. Due to its inertness and unique properties such as elasticity and durability, silicone is widely used in medical applications such as medical devices and biomedical engineering. Additive manufacturing (AM)/3D Printing could expand the potential of silicone even further and allow for the precise & fast fabrication of complex silicone structures. However, development of additive manufacturing (AM) systems for processing silicone involves substantial challenges, due to its high viscosity, low elastic modulus, and the need for support structures during printing. Nonetheless, recent advancements in additive manufacturing techniques enabled 3D printing of silicone possible, establishing it as a rapidly growing and exciting field in biomedical research. Recent research shows that silicone 3D printing can be successfully utilised for the manufacture of sensors, wearable devices, anatomical models, implants, microfluidic devices, and more. This review provides a thorough analysis of the current state of silicone 3D printing for medical applications, highlighting its limitations as well as the promising opportunities it offers for future advancements.

INTRODUCTION:Often used interchangeably with 'additive manufacturing,' 3D printing involves creating a three-dimensional (3D) object from a digital model, by building successive layers of raw material. By adding material to only where it is needed, 3D printing has the potential to save considerable resources compared to 'subtractive manufacturing' which involves removing the excessive materials to make the necessary part. In addition to cost-savings, 3D printing offers flexibility in design and the possibility of personalizing a 3D-printed object to a patient's anatomy. Some of the potential applications of personalized 3D-printed devices include custom-made surgical instruments, guides, and implants. AREAS COVERED:The UK Medical Device Regulations (MDR) 2002, UK Medical Device Amendment Regulations (MDAR) 2026 (draft), the EU Medical Device Regulation (MDR) 2017/745, and Federal Food, Drug, and Cosmetic Act provide comprehensive guidance and regulations for medical devices. However, there is currently a knowledge gap, where researchers of 3D-printed customized medical devices lack complete understanding of the need for regulation, and step-by-step guidance specific to the field. This article provides practical guidance for researchers manufacturing customized 3D-printed medical devices. EXPERT OPINION:Artificial intelligence (AI) is likely to be a major aid for researchers and device manufacturers for completing applications in different jurisdictions.

Microsurgical training requires high-fidelity vascular models to replace traditional training on living animals or cadavers, which face increasing ethical and logistical constraints. This review evaluates the current state of engineered synthetic blood vessel models designed to accurately mimic the mechanical and haptic properties of human vessels. Following a systematic literature search, data were extracted and analyzed from 26 primary studies. The models were categorized into three primary technological groups: 3D-printed/post-processed structures, spinning technologies, and biomimetic/hybrid grafts. Key mechanical benchmarks, including burst pressure (BP) and suture retention force (SRF), were compared against human physiological references. The analysis indicates that while silicone and elastomers provide excellent durability and geometric precision, hydrogel-based and multi-layered hybrid models offer superior 'needle-feel' and biomimetic compliance. Mechanical validation remains heterogeneous across the 26 studies. However, BP and suture retention are emerging as critical benchmarks for assessing model fidelity. Future developments should focus on standardized, multi-material models that integrate pulsatile flow systems. Such advancements are essential to bridge the gap between benchtop simulation and clinical reality, ultimately facilitating the replacement of animal models in microsurgical education.

BACKGROUND:Dedicated robotic-assisted microsurgical systems (RAMS), including the Symani Surgical System and MUSA, were developed to overcome physiological tremor, surgeon fatigue, and restricted maneuverability in deep surgical fields. Existing reviews of robotic plastic surgery largely span heterogeneous applications beyond microsurgery or lack structured risk-of-bias appraisal specific to dedicated microsurgical platforms. This review systematically synthesizes clinical outcomes, learning-curve dynamics, and technological features of dedicated RAMS platforms in microsurgery, incorporating structured risk-of-bias appraisal to clarify the evidence base and inform clinical adoption. METHODS:Studies published 2015-2025 were identified through PubMed, Embase, Scopus, and Web of Science (PROSPERO CRD420261320086). Following independent screening, 21 studies were included, assessing free flap survival, anastomotic patency, complications, operative times, and learning-curve metrics. RESULTS:Free flap reconstruction showed high survival (96%-100%); supermicrosurgical anastomosis patency was 96.6%-100%. Robotic anastomosis times fell 51%-66% with experience (largest reduction 66.1%, for deep-plane arterial anastomosis), though times remained longer than manual benchmarks even after the learning phase (e.g., 25.3 ± 12.3 vs. 14.1 ± 4.3 min for mixed procedures). Conversion/failure was infrequent (0%-4.3%). Motion scaling (up to 20×) and tremor filtration were consistent advantages; haptic feedback remained universally absent. CONCLUSION:Dedicated RAMS platforms are safe and effective for micro- and supermicrosurgical reconstruction, non-inferior to manual techniques. Initial time penalties resolve with experience. Future research should prioritize randomized controlled trials, standardized outcome measures, and cost-effectiveness analyses.

Automated analysis of spinal CT involves localising, identifying and segmenting individual vertebrae. Challenges due to similarity of vertebral structures, pathological variations and rare cases (e.g. transitional vertebrae), lead to misclassifications. Prior approaches typically address segmentation and localisation separately, with multi-stage pipelines, disregarding their intrinsic relationship. This paper introduces VerTE-MT, a novel singlestage, multi-task (MT) learning framework that concurrently performs vertebrae segmentation and centroid localisation. The proposed architecture integrates a shared volumetric encoder, a Vision Transformer bottleneck for global spatial reasoning, and dual decoders for segmentation and localisation. Entropy-guided sampling dynamically prioritises under-represented vertebrae (e.g L6) enabling efficient MT learning and enhancing performance on pathological anatomies (e.g. scoliotic). In the VerSe'20 public and hidden test set, VerTE-MT outperforms existing singlestage methods, achieving average Dice score of 84.18% and 85.45% for vertebral column segmentation, 81.03% and 75.96% in L6, while reducing segmentation boundary errors with a decrease in Hausdorff Distance (HD) of up to 4.62mm and 4.04mm, respectively. It also obtains robust localisation maintaining a mean error below 10mm across spinal regions. Zero-shot validation on cadaveric and clinical CT scoliotic datasets, with mean Dice of 83.03% and 65.17% respectively, highlights VerTE-MT's potential on unseen pathological cases.

Engineering vascularised skin substitutes capable of supporting both macro- and microvascular perfusion remains a critical unmet challenge in reconstructive surgery. Here, we describe VascuDerm, a hierarchically vascularised dermal construct assembled using LATTICE (Living Assembly through Templated Tissue Integration and Construct Engineering) a modular biofabrication strategy combining coaxial bioprinting, sacrificial tungsten-wire templating and fibroblast-laden hydrogel layering. VascuDerm integrates a central perfusable vein-like macrochannel with spatially distributed capillary-mimicking microvessels (CMMs), all embedded within a human dermal fibroblast-rich matrix and cellularised with adipose-derived stem cell (ADSC)-derived endothelial and smooth muscle cells. Rheologically optimised VascuBiomatrix supported robust print fidelity and sustained cell viability across all compartments. Dynamic perfusion culture significantly enhanced endothelial organisation, extracellular matrix deposition, barrier function and mechanical integrity compared with static controls. Gene expression analysis confirmed progressive upregulation of lineage-specific vascular and stromal markers under flow conditioning. The chick chorioallantoic membrane assay demonstrated active angiogenic recruitment and early host-construct integration. Collectively, LATTICE provides a scalable, clinically adaptable platform for generating perfusion-competent hierarchical vascular constructs with direct applications in disease modelling, drug screening and translational reconstructive surgery.

Ethnopharmacological relevance Clove is used in Indian and Chinese traditional medicine for viral diseases. Palmarosa essential oils have been traditionally used in India and Southeast Asia since ancient times and have made considerable use of them. In New Caledonia, niaouli oil is used in aromatherapy and pharmaceutical formulations to treat pain and viral diseases. Since ancient times, the South Pacific region has used tamanu oil as a traditional medicine to treat a wide range of skin conditions. Aim of the study This study investigates the antiviral properties of essential oils (EOs) from Eugenia aromaticum (clove oil, CL-R030424005 (CL)), Cymbopogon martinii (palmarosa oil, PA-R040923008 (PA)), Melaleuca viridiflora (niaouli oil, NI-R290124038 (NI)), and Calophyllum inophyllum (tamanu oil, TA-F140224029 (TA)), and their mixture against human papillomavirus (HPV) infection. Materials and methods A D-optimal mixture design is used to determine the most effective EO combinations and evaluate their antiviral efficacy through IC50 values. The EOs were tested for their ability to inhibit HPV-related oncogenes (L1, L2, E1, E2, E6, and E7) in HPV-infected cells with ELISA, qPCR, and Western blot analyses. Results and discussion: The optimal mixture (31.5% CL, 31.5% PA, and 37% NI) demonstrated significant antiviral activity, reducing viral replication and protein expression in HPV-infected cells. Ex-vivo permeation studies showed higher permeation rates in healthy tissues compared to infected ones, indicating the oils' potential in targeted drug delivery. Additionally, cytotoxicity assessments confirmed the safety of the EOs at effective concentrations in HPVCs, DoTc2, and HEKa cells. Molecular docking studies further elucidated the interactions between EO components and HPV proteins, supporting their antiviral mechanisms. Conclusion These findings suggest that EOs, particularly in optimized combinations, offer a promising natural supportive treatment for managing HPV infections, warranting further in vivo animal tests and clinical trials.

PurposeThe study conducts a comparative analysis between two prominent methods for fabricating composites for bone scaffolds—the (solid) solvent method and the solvent-free (melting) method. While previous research has explored these methods individually, this study provides a direct comparison of their outcomes in terms of physicochemical properties, cytocompatibility, and mechanical strength. We also analyse their workflow and scalability potentials.Design/methodology/approachPolycaprolactone (PCL) and hydroxyapatite (HA) composites were prepared using solvent (chloroform) and melting (180°C) methods, then 3D-printed using an extrusion-based 3D printer to fabricate scaffolds (8 × 8 × 4 mm). Rheology, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), accelerated degradation, mechanical/compression test, wettability/contact angle, live/dead assay, and DNA quantification (Picogreen) assays were evaluated.FindingsThe study finds that scaffolds made via the solid solvent method have higher mechanical strength and degradation rate as compared to those from the melting method, while both methods ensure adequate cytocompatibility and homogenous hydroxyapatite distribution, supporting their use in bone tissue engineering.OriginalityThis research investigates the utility of chloroform as a solvent for PCL composite in a direct comparison with the melting method. It also highlights the differences in workflows between the two methods and their scalability implications, emphasizing the importance of considering workflow efficiency and the potential for automation in scaffold fabrication processes for bone tissue engineering applications.

Novel therapeutic strategies are essential for enhancing efficacy and accelerating the treatment of diabetes mellitus. This investigation focused on incorporating empagliflozin into a composite of polylactic acid and polycaprolactone, resulting in the fabrication of drug-loaded fibrous patches (DFPs) for transdermal application, both by electrospinning (ES) and by pressurized gyration (PG). Scanning electron microscopy results revealed that DFPs generated through the PG method exhibited smaller diameters and a larger surface area than ES. Fourier-transform infrared spectroscopy and X-ray powder diffraction analyses confirmed the successful encapsulation of the drug in both DFPs. DFPs/PG exhibited a controlled release of 98.7 ± 1.3% of the total drug over 14 days, while DFPs/ES released 98.1 ± 2.1% in 12 days, according to in vitro drug release studies. This study underscores that the PG method can generate DFPs with extended controlled release. 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide test results validate the biocompatibility of DFPs, affirming their lack of adverse effects on human dermal fibroblast cell viability. Consequently, DFPs can be manufactured for transdermal administration using PG, exhibiting similar characteristics to ES but with the added advantage of mass production capability.

Dropped Head Syndrome (DHS) is a neurological condition characterized by severe head and neck muscle atrophy, leading to difficulties in maintaining a straight gaze and experiencing severe neck pain during daily activities. Standard off-the-shelf cervical orthotic devices (Neck Collars) often fail to provide adequate support for patients with DHS. This feasibility study aimed to develop and implement a novel feedback-incorporated workflow for creating personalized 3D printed (Powder Bed Fusion) cervical orthotic devices for six DHS patients with varying pathologies. A tailored workflow was devised and executed to produce bespoke 3D printed cervical orthotic devices for 6 DHS patients. The effectiveness of the collars in supporting patients during activities and reducing neck pain was assessed quantitatively and qualitatively using validated patient support questionnaires, Neck Disability Index, Visual Analog Score for Neck Pain, Global Cervical Angles (GCA), and Vertical Chin Brow Angles (VCBA) before and after intervention. Various clinical and design parameters were analysed to evaluate the collars’ efficacy in supporting patients and reducing neck pain. Patients exhibited an increase in GCA and a decrease in VCBA when using the collars as compared to their previous condition without those. The Visual Analog Score for Neck Pain decreased over the 6-month follow-up period, indicating positive implementation of the bespoke collars. The personalized design and functionality of the 3D printed collars significantly improved patients’ quality of life, representing a significant advancement in rehabilitative and supportive healthcare interventions. This pilot study lays the groundwork for further large-scale cohort studies.

Epilepsy is one of the oldest neurological disorders discovered by mankind. This condition is firmly coupled with unprovoked seizures stimulated by irrepressible neuroelectrical blasts. Orally taken valproate family has been employed for prophylactic management; however, oral administration is not applicable for critical scenarios, thus calling for medication routes fulfilling necessities of immediate innervation. In order to address this shortcoming, sodium valproate entrapped in poly(ethylene oxide)/polyvinylpyrrolidone (PEO/PVP) nanofibrous patches was developed with the aim of sublingual drug delivery. Initially, the production process was designed and optimized via the central composite design (CCD). Nanofiber fabrication was accomplished with a novel device by using the pressurized gyration method. Fabricated biomaterials were chemically, spatially, and thermally inspected. The beanless and homogeneous appearance of both virgin and impregnated nanofibrous patches was morphologically demonstrated via scanning electron microscopy. Additionally, adequately oro-dispersed impregnated patches released more than 90% of their drug content in under a minute. Following in vitro cyto-safety assurance acquired through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay on SH-SY5Y neuroblastoma cells, the protective antiepileptic effect of impregnated patches was affirmed in vivo via pentylenetetrazole kindled-induced Mus musculus animal modeling. The parameter of in vivo behavioral evaluation was the Racine scoring system. Moreover, histopathological distinctions detected between different test groups were highlighted via fluorescence staining. Finally, the oxidative stress was determined according to quantitative variations of malondialdehyde, glutathione, superoxide dismutase, and catalase levels. The overall conclusion herein suggests that sodium valproate-loaded PEO/PVP nanofibrous patches strikingly prevented behavioral, structural, and oxidative deteriorations caused by pentylenetetrazole.

Human adipose derived stem cells (ADSCs) are being explored for the repair of craniofacial defects due to their multi-differentiation potential and ease of isolation and expansion. Crucial to using ADSCs for craniofacial repair is the availability of materials with appropriate biomechanical properties that can support their differentiation into bone and cartilage. We tested the hypothesis that different modifications of chemical groups on the surface of a nanocomposite polymer could increase human ADSC adhesion and selectively enhance their osteogenic and chondrogenic differentiation. We show that the COOH modification significantly promoted initial cell adhesion and proliferation over 14days compared to NH2 surfaces. Expression of focal adhesion kinase and vinculin was enhanced after plasma surface polymerisation at 24h. The COOH modification significantly enhanced chondrogenic differentiation as indicated by up-regulation of aggrecan and collagen II transcripts. In contrast, NH2 group functionalised scaffolds promoted osteogenic differentiation with significantly enhanced expression of collagen I, alkaline phosphatase and osteocalcin both at the gene and protein level. Finally, chorioallantoic membrane grafting demonstrated that both NH2 and COOH functionalised scaffolds seeded with ADSCs were biocompatible and supported vessel ingrowth apparently to a greater degree than unmodified scaffolds. In summary, our study shows the ability to direct ADSC chondrogenic and osteogenic differentiation by deposition of different chemical groups through plasma surface polymerisation. Hence this approach could be used to selectively enhance bone or cartilage formation before implantation in vivo to repair skeletal defects.STATEMENT OF SIGNIFICANCE:Human adipose derived stem cells (hADSCs) are an exciting stem cell source for regenerative medicine due to their plentiful supply and ease of isolation. However, the optimal environmental cues to direct stem cells towards certain lineages change have to has not been identified. We have shown that by modifying the surface of the scaffold with specific chemical groups using plasma surface polymerisation techniques we can control ADSCs differentiation. This study shows that ADSCs can be differentiated towards osteogenic and chondrogenic lineages on amine (NH2) and carboxyl (COOH) modified scaffolds respectively. Plasma polymerisation can be easily applied to other biomaterial surfaces to direct stem cell differentiation for the regeneration of bone and cartilage.

Muscle spindles are key proprioceptive mechanoreceptors composed of intrafusal fibres that regulate kinaesthetic sensations and reflex actions. Traumatic injuries and neuromuscular diseases can severely impair the proprioceptive feedback, yet the regenerative potential and cell-matrix interactions of muscle spindles remain poorly understood. There is a pressing need for robust tissue-engineered models to study spindle development, function and regeneration. Traditional approaches, while insightful, often lack physiological relevance and scalability. Three-dimensional (3D) bioprinting offers a promising approach to fabricate biomimetic, scalable, and animal-free muscle spindle constructs with controlled cellular architecture. Various bioprinting techniques – including inkjet, extrusion, digital light projection and laser-assisted bioprinting – have been explored for skeletal muscle fabrication, but replicating intrafusal fibre complexity remains a challenge. A major challenge lies in bioink development, where biocompatibility, printability and mechanical strength must be balanced to support intrafusal fibre differentiation and proprioceptive function. Recent molecular insights into spindle anatomy, innervation and extracellular matrix composition are shaping biofabrication strategies. This review discusses the current state of muscle spindle modelling, the application of 3D bioprinting in intrafusal fibre engineering, key challenges and future directions.

Among numerous dysfunctions associated with Alzheimer's disease, cholinergic deficiency has been postulated as evidently influential. Despite donepezil's ability to decelerate disease progression, drug's pharmacokinetics interfere with its efficacy and, therefore, pharmacological outcome. Given the recent advancements in the pharmaceutical nanotechnology, the associated shortcomings can be resolved by using nanomedicine. Herein, this project developed donepezil-loaded polymeric nanospheres consisted of chitosan (Cs) and chitosan/polyethylene glycol (Cs/PEG) composition that provided controlled drug release for 12 h. The morphological investigation showed well-defined spherical nanospheres with internal solid core covered by a porous surface. The lowest mean particle size observed in virgin Cs/PEG nanospheres was 136.6 +/- 17.5 nm. Molecular, structural, and thermal investigations proposed high compatibility between the drug and matrix. The KorsmeyerPeppas kinetic release model was observed in drug-loaded nanosphere types. In vitro cytosafety was confirmed with a MTT assay on human neuroblastoma SH-SY5Y cell line. Additionally, the potential anti-Alzheimer efficacy of the impregnated nanospheres were demonstrated on in vitro A(31-42-induced Alzheimer model. The overall conclusion suggests the feasibly, safety, and efficacy of the developed drug delivery system.

Stromal vascular fraction (SVF) from adipose tissue is a rich and accessible source of regenerative cells, including adipose-derived stem cells (ADSCs). SVF is most commonly isolated from lipoaspirate via enzymatic digestion, a process that is costly and considered ‘more than minimal manipulation’ by the United States Food and Drug Administration. In contrast, mechanically based isolation techniques have gained attention as a simpler, faster, and regulatory-compliant alternative, making them increasingly appealing for clinical applications. This systematic review and meta-analysis aimed to evaluate the outcomes of mechanical methods for harvesting SVF from human adipose tissue. Key parameters assessed included cell yield, viability, surface marker expression, and differentiation capacity. Additionally, split-sample studies were analysed descriptively to compare mechanical and enzymatic isolation approaches, thereby reducing variability in tissue source and preparation. A narrative synthesis was performed for all eligible studies (k = 22), and a single-arm meta-analysis of pooled outcomes of mechanical protocols was conducted for total cell yield and expression of CD34, CD73, and CD105 markers, depending on data availability. Mechanical isolation approaches varied considerably, but most high-performing protocols involved dedicated devices or systems. Meta-analysis revealed a pooled mean SVF cell yield of 11.96 × 104 cells/ml. The pooled expression levels of CD105 (4.08

Abstract Aim This study compares the precision, accuracy, and user experience of 3D body surface scanning of human subjects using the Artec Leo hand-held scanner and the iPad Pro as 3D scanning devices for capturing cervical and craniofacial data. The investigation includes assessing methods for correcting 'dropped head syndrome' during scanning, to demonstrate the ability of the scanner to be used to reconstruct body surface of patients. Methods Eighteen volunteers with no prior history of neck weakness were scanned three times in three different positions, using the two different devices. Surface area, scanning time, and participant comfort scores were evaluated for both devices. Precision and accuracy were assessed using Mean Absolute Deviation (MAD), Mean Absolute Percentage Error (MAPE), and Intra-Class Correlation Coefficients (ICC). Results Surface area comparisons revealed no significant differences between devices and positions. Scanning times showed no significant difference between devices or positions. Comfort scores varied across positions. MAD analysis identified chin to chest measurements as having the highest variance, especially in scanning position 3. However, no statistical differences were found. MAPE results confirmed accuracy below 5% error for both devices. ICC scores indicated good reliability for both measurement methods, particularly for chin to chest measurements in positions 1 and 3. Conclusion The iPad Pro using the Qlone app demonstrates a viable alternative to the Artec Leo, particularly for capturing head and neck surface area within a clinical setting. The scanning resolution, with an error margin within ±5%, is consistent with clinically accepted standards for orthosis design, where padding and final fit adjustments allow for bespoke devices that accommodate patient comfort. This study highlights the comparative performance of the iPad, as well as suggests two methods which can be used within clinics to correct head drop for scanning.