Tissue Replacement Research Articles

Abstract 4136452: Acute Cardiac Function Change After Catheter Ablation of Ventricular Arrhythmias in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder characterized by fibrofatty replacement of myocardial tissue, creating areas of electrical heterogeneity and increasing the risk of ventricular arrhythmias (VAs) and sudden cardiac death (SCD). Catheter ablation is commonly performed in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) for management of ventricular arrhythmias (VAs). Whether catheter ablation affects cardiac function post-procedurally is uncertain. Research Question: Does catheter ablation for ARVC result in acute change in cardiac function? Goals/Aims: To assess the impact of catheter ablation for VAs on cardiac function in the acute post-procedure setting. Methods: This retrospective study included patients with ARVC who underwent catheter ablation for VAs at Mayo Clinic. Cardiac function was assessed on pre- and post-procedure transthoracic echocardiograms (TTEs). Post-procedure TTEs were obtained within 4 weeks after the ablation procedure. Right ventricular (RV) enlargement and systolic dysfunction were evaluated as continuous variables (0=none, 1=mild, 2=mild-moderate, 3=moderate, 4=moderate-severe, 5=severe). Results: The study included 32 patients who underwent a total of 44 ablations. Mean age at the time of ablation was 49±16 years, and 24 (75%) were male. After a mean follow-up duration of 2.6±5.5 days, there was a significant worsening in mean RV dysfunction (1.6±1.5 to 2.0±1.4, P = 0.001). There were no significant changes in mean left ventricular ejection fraction (LVEF), left ventricular (LV) dimensions, and RV size. 6 (14%) patients had a >5% decline in LVEF, and 14 (32%) patients had worsening RV function. Transient inotropic support was required in 4 (9%) patients. Conclusion(s): This study is the first to assess the acute impact of catheter ablation for VAs on cardiac function in ARVC patients. These results underscore the importance of careful post-procedure monitoring and planning of the ablation target in these patients to avoid excessive ablation and therefore impairment in cardiac function.

Designing biphasic nanocellulose hydrogels to mimic the complex cartilage-bone interface

Osteochondral lesions, which affect both the cartilage and the bone, present significant challenges in treatment due to the complex mechanical and biochemical properties of these tissues. A crucial consideration in developing tissue replacements for these lesions is the simultaneous regeneration of cartilage and calcified cartilage, which forms the transition zone to bone. Our current study aims to fabricate a bilayer polymeric hydrogel designed not only to support cartilage regeneration but also to serve as an interface between cartilage and bone. The bilayer hydrogel was created by combining oxidized bacterial nanocellulose, gelatin, and alginate in one layer, while the other layer consisted of the same three biopolymers and hydroxyapatite. The bacterial nanocellulose was effectively oxidized (20%) with sodium periodate and then mineralized with calcium and phosphorus (Ca/P ratio = 0.97), as confirmed by EDX analysis. Remarkably, both layers of the biphasic hydrogel demonstrated cytocompatibility with chondrocytes. Moreover, the addition of hydroxyapatite significantly improved the mechanical strength from 72 kPa (OBC/Gel/Alg) to 90 kPa (MOBC/Gel/Alg). This bilayer hydrogel holds promise for promoting bone-cartilage integration and has the potential to contribute to the healing of osteochondral defects, offering new possibilities in the field of orthopedic tissue engineering and regenerative medicine.

Personalized in silico model for radiation-induced pulmonary fibrosis.

Radiation-induced pulmonary fibrosis (RIPF) is a severe late-stage complication of radiotherapy (RT) to the chest area, typically used in lung cancer treatment. This condition is characterized by the gradual and irreversible replacement of healthy lung tissue with fibrous scar tissue, leading to decreased lung function, reduced oxygen exchange and critical respiratory deficiencies. Currently, predicting and managing lung fibrosis post-RT remains challenging, with limited preventive and treatment options. Accurate prediction of fibrosis onset and progression is therefore clinically crucial. We present a personalized in silico model for pulmonary fibrosis that encompasses tumour regression, fibrosis development and lung tissue remodelling post-radiation. Our continuum-based model was developed using data from 12 RT-treated lung cancer patients and integrates computed tomography (CT) and dosimetry data to simulate the spatio-temporal evolution of fibrosis. We demonstrate the ability of the in silico model to capture the extent of fibrosis in the entire cohort with a less than 1% deviation from clinical observations, in addition to providing quantitative metrics of spatial similarity. These findings underscore the potential of the model to improve treatment planning and risk assessment, paving the way for more personalized and effective management of RIPF.

Bioresorbable composites based on magnesium and hydroxyapatite for use in bone tissue engineering: focus on controlling and minimizing corrosion activity

A biodegradable matrix with a significant content of bioactive components can be applied for bone tissue replacement, including load-bearing applications in orthopedic surgery. The study outlines the optimized procedure for the production of bioresorbable magnesium-hydroxyapatite (Mg-HA) composites and their corrosion resistance properties. Composites were meticulously crafted by combining pure magnesium with microwave-synthesized hydroxyapatite nanopowder. Sintering occurred via spark plasma sintering technology (SPS). To align the degradation time of the resulting composites with bone remodeling, the corrosion resistance of SPS materials was enhanced through the application of plasma electrolytic oxidation (PEO) and polycaprolactone (PCL) spin-coating methods. The protective properties, morphology dynamics, and composition due to surface treatment and corrosion propagation were investigated using Electrochemical Impedance Spectroscopy (EIS), Potentiodynamic Polarization (PDP), hydrogen evolution tests, Scanning Electron Microscopy (SEM), Energy-dispersive X-ray (EDX) as well as X-ray diffraction (XRD) analysis. Analytics of the physicochemical properties data of the formed coatings indicate a significant improvement in protective characteristics and deceleration of the corrosive degradation of the samples. The application of polycaprolactone to the PEO coating leads to a decrease in the corrosion current compared to uncoated magnesium composites by more than three orders of magnitude: from 1 10-5 to 2 10-9 A cm-2. During long-term exposure of samples to 0.9 % NaCl solution, it was found that coating reduced the rate of corrosion degradation of samples from 1.5 to 80 times compared to an unprotected Mg-HA composite and sintered magnesium. Mg-HA composites treated with PEO exhibit potential application as bioactive and biodegradable materials for orthopedic implants and fixation devices.

Decomposition and Changes in InVivo Post-HA Filler Injection: A Review.

Hyaluronic acid (HA) fillers are widely used in aesthetic medicine, but their invivo behavior and long-term effects are not fully understood. To review the decomposition and changes occurring in the body following HA filler injections, focusing on crosslinking agents, degradation processes, and tissue responses. This review analyzed oxidative and enzymatic degradation processes of HA fillers, evaluated the impact of 1,4-Butanediol Diglycidyl Ether (BDDE) crosslinking, and examined histological changes post-injection. Uncrosslinked HA degrades rapidly due to endogenous hyaluronidase, while crosslinked HA undergoes slower degradation via free radicals and hyaluronidase. Complete cross-linking (C-MoD) showed better durability compared to partially cross-linked BDDE (P-MoD). The concept of modification efficiency (MoE) was proposed to optimize filler safety and viscoelastic properties. Histological analysis revealed collagen capsule formation and autologous tissue replacement, affecting long-term outcomes. The degree of chemical modification (MoD) influences filler durability and safety, with concerns raised about potential delayed immune reactions from accumulated pendent BDDE. Clinicians should consider injection site, tissue conditions, and filler properties for safe and effective HA filler use. Emphasizing thorough BDDE removal and optimal crosslinking can enhance treatment safety and efficacy. The balance between achieving desired viscoelastic properties and minimizing potential risks is crucial. Future studies should include diverse ethnic groups to validate findings and further explore long-term tissue responses to HA fillers.

Kallistatin and Glypican-3 as Reliable Biomarkers for the Prediction of Liver Cirrhosis

Background: Cirrhosis is a condition in which the liver does not function properly due to long-term damage, this damage is characterized by the replacement of normal liver tissue by scar tissue. Objective: In the present study, an attempt was made to explore the role of kallistatin (KAL) and glypican3 (GPC3) as a predictor of liver cirrhosis (LC) in patients with hepatitis, non-alcoholic fatty acid and autoimmune diseases. Materials and Methods: This case–control study included 98 cirrhotic patients (34 patients with hepatitis B & A, 31 patients with non-alcoholic fatty liver disease and 33 patients with autoimmune) and 30 apparently healthy individuals. The laboratory investigations were performed, and the serum KAL and GPC3 were measured in all volunteers. Results: Serum levels of KAL, GPC3, and TAC were significantly decreased and MDA increased (p<0.01) in patients with LC as compared to control. The significant difference can also be indicatly seen in patients with hepatitis > non-alcoholic fatty acid > autoimmune diseases, respectively. The area under the curve (AUC) results obtained indicate that Kal and GPC3 could potentially be used as greater predictive biomarkers in LC with hepatitis ˃ NAFLD ˃ autoimmune diseases (Kal: AUC= -0.97, -0.91, -0.88; Gyp3: AUC= 0.89, 0.84, 0.79, respectively). Conclusion: Incorporating KAL and GPC3 screening into routine check-ups for patients with hepatitis, non-alcoholic fatty liver, and autoimmune diseases could aid in the early detection and prevention of LC-associated complications.

Biomechanical considerations of chemical structure and biosafety of current ceramic biomaterials for dentistry: review and outlook of the current state of the art.

Biomaterial refers to any material, non-pharmaceutical or combination of substances of synthetic or natural origin used for any period independently or as part of a system for the purpose of healing, assisting the growth or replacement of tissues, organs or functions of the body. It is an unsustainable material that interacts with biological systems. Before being produced a biomaterial goes through a sequence of steps, which includes: 1) the definition of the problem that the material will be called to solve (treatment, replacement of the instrument, aesthetic reasons); 2) design of the device, composition and control of materials (mechanical properties, toxicity, biological response, corrosion resistance, interaction with proteins, cells and tissues), manufacture, sterilization and standardization; 3) control of the device (in experimental animals, in vitro) clinical studies, studies; and 4) monitor its long-term use in vivo, in vitro and in patients. Research for ceramic materials is evolving and because they can be porous or glassy, they find applications in medicine and biotechnology, as they can be used as fillers, covering materials and scaffolds. Therefore, ceramic biomaterials are widely used not only in the field of orthopedic and maxillofacial surgery but also in dentistry as for dental prostheses. Materials monitoring technologies allow us to monitor the three-dimensional development in space, as well as imperfections or micro-cracks in the ceramic.

Research Status and Safety Considerations of Animal-Derived Mesh Products

With the development of the economy and technological progress, more and more animal-derived mesh products are being utilized in the medical field for tissue and organ repair and replacement. Owing to the complexity of their structure and production process, these animal-derived meshes still face several challenges in practical applications, such as insufficient mechanical strength, rapid degradation rates, and the detection of harmful leachable substances. Among these challenges, the production process is a key factor affecting product quality. This paper reviews the key aspects of the production process and quality control for animal-derived meshes in China, offering new insights for the quality control and regulatory oversight of such products.

High hydrostatic pressure treatment for advanced tissue grafts in reconstructive head and neck surgery.

The increasing importance of regenerative medicine has resulted in a growing need for advanced tissue replacement materials in head and neck surgery. Allo- and xenogenic graft processing is often time-consuming and can deteriorate the extracellular matrix (ECM). High hydrostatic pressure (HHP)-treatment could allow specific devitalization while retaining the essential properties of the ECM. Porcine connective tissue and cartilage were HHP-treated at 100-400 MPa for 10 min. Structural modifications following HHP-exposure were examined using electron microscopy, while devitalization was assessed through metabolism and cell death analyses. Furthermore, ECM alterations and decellularization were evaluated by histology, biomechanical testing, and DNA content analysis. Additionally, the inflammatory potential of HHP-treated tissue was evaluated in vivo using a dorsal skinfold chamber in a mouse model. The devitalization effects of HHP were dose-dependent, with a threshold identified at 200 MPa for fibroblasts and chondrocytes. At this pressure level, HHP induced structural alterations in cells, with a shift toward late-stage apoptosis. HHP-treatment preserved ECM structure and biomechanical properties, but did not remove cell debris from the tissue. This study observed a pressure-dependent increase of markers suggesting the occurrence of immunogenic cell death. In vivo investigations revealed an absence of inflammatory responses to HHP-treated tissue, indicating a favorable biological response to HHP. In conclusion, application of HHP devitalizes fibroblasts and chondrocytes at 200 MPa while retaining the essential properties of the ECM. Prospectively, HHP may simplify the preparation of allo- and xenogenic tissue replacement materials and increase the availability of grafts in head and neck surgery.

ADAMTS12 promotes fibrosis by restructuring extracellular matrix to enable activation of injury-responsive fibroblasts.

Fibrosis represents the uncontrolled replacement of parenchymal tissue with extracellular matrix (ECM) produced by myofibroblasts. While genetic fate-tracing and single-cell RNA-Seq technologies have helped elucidate fibroblast heterogeneity and ontogeny beyond fibroblast to myofibroblast differentiation, newly identified fibroblast populations remain ill defined, with respect to both the molecular cues driving their differentiation and their subsequent role in fibrosis. Using an unbiased approach, we identified the metalloprotease ADAMTS12 as a fibroblast-specific gene that is strongly upregulated during active fibrogenesis in humans and mice. Functional in vivo KO studies in mice confirmed that Adamts12 was critical during fibrogenesis in both heart and kidney. Mechanistically, using a combination of spatial transcriptomics and expression of catalytically active or inactive ADAMTS12, we demonstrated that the active protease of ADAMTS12 shaped ECM composition and cleaved hemicentin 1 (HMCN1) to enable the activation and migration of a distinct injury-responsive fibroblast subset defined by aberrant high JAK/STAT signaling.

Precision and efficacy of RNA-guided DNA integration in high-expressing muscle loci

Gene replacement therapies primarily rely on adeno-associated virus (AAV) vectors for transgene expression. However, episomal expression can decline over time due to vector loss or epigenetic silencing. CRISPR-based integration methods offer promise for long-term transgene insertion. While the development of transgene integration methods has made substantial progress, identifying optimal insertion loci remains challenging. Skeletal muscle is a promising tissue for gene replacement owing to low invasiveness of intramuscular injections, relative proportion of body mass, the multinucleated nature of muscle, and the potential for reduced adverse effects. Leveraging endogenous promoters in skeletal muscle, we evaluated two highly expressing loci using homology-independent targeted integration (HITI) to integrate reporter or therapeutic genes in mouse myoblasts and skeletal muscle tissue. We hijacked the muscle creatine kinase (Ckm) and myoglobin (Mb) promoters by co-delivering CRISPR-Cas9 and a donor plasmid with promoterless constructs encoding green fluorescent protein (GFP) or human Factor IX (hFIX). Additionally, we deeply profiled our genome and transcriptome outcomes from targeted integration and evaluated the safety of the proposed sites.This study introduces a proof-of-concept technology for achieving high-level therapeutic gene expression in skeletal muscle, with potential applications in targeted integration-based medicine and synthetic biology.

Tough, Slippery, and Low-Permeability Multilayer Hydrogels Modified by Anisotropic Fiber Membrane for Soft Tissue Replacement.

Hydrogels with sustained lubrication, high load-bearing capacity, and wear resistance are essential for applications in soft tissue replacements and soft material devices. Traditional tough or lubricious hydrogels fail to balance the lubrication and load-bearing functions. Inspired by the gradient-ordered multilayer structures of natural tissues (such as cartilage and ligaments), a tough, smooth, low-permeability, and low-friction anisotropic layered electrospun fiber membrane-reinforced hydrogel was developed using electrospinning and annealing recrystallization. This hydrogel features a stratified porous network structure of varying sizes with tightly bonded interfaces, achieving an interfacial bonding toughness of 1.6 × 103 J/m2. The anisotropic fiber membranes, mimicking the orderly fiber structures within soft tissues, significantly enhance the mechanical properties of the hydrogel with a fracture strength of 20.95 MPa, a Young's modulus of 29.64 MPa, and a tear toughness of 37.94 kJ/m2 and reduce its permeability coefficient (6.1 × 10-17 m4 N-1 s-1). Meanwhile, the hydrogel demonstrates excellent solid-liquid phase load-bearing characteristics, which can markedly improve the tribological performance. Under a contact load of 4.1 MPa, the anisotropic fiber membrane-reinforced hydrogel achieves a friction coefficient of 0.036, a 219% reduction compared with pure hydrogels. Thus, the superior load-bearing and lubricating properties of this layered hydrogel underscore its potential applications in soft tissue replacements, medical implants, and other biomedical devices.

Characterization of pediatric porcine pulmonary valves as a model for tissue engineered heart valves

Heart valve tissue engineering holds the potential to transform the surgical management of congenital heart defects affecting the pediatric pulmonary valve (PV) by offering a viable valve replacement. While aiming to recapitulate the native valve, the minimum requirement for tissue engineered heart valves (TEHVs) has historically been adequate mechanical function at implantation. However, long-term in situ functionality of TEHVs remains elusive, suggesting that a closer approximation of the native valve is required. The realization of biomimetic engineered pediatric PV is impeded by insufficient characterization of healthy pediatric tissue. In this study, we comprehensively characterized the planar biaxial tensile behaviour, extracellular matrix (ECM) composition and organization, and valvular interstitial cell (VIC) phenotypes of PVs from piglets to provide benchmarks for TEHVs. The piglet PV possessed an anisotropic and non-linear tension-strain profile from which material constants for a predictive constitutive model were derived. The ECM of the piglet PV possessed a trilayer organization populated by collagen, glycosaminoglycans, and elastin. Biochemical quantification of ECM content normalized to wet weight and DNA content of PV tissue revealed homogeneous distribution across sampled regions of the leaflet. Finally, VICs in the piglet PV were primarily quiescent vimentin-expressing fibroblasts, with a small proportion of activated α-smooth muscle actin-expressing myofibroblasts. Overall, piglet PV properties were consistent with those reported anecdotally for pediatric human PVs and distinct from those of adult porcine and human PVs, supporting the utility of the properties determined here to inform the design of tissue engineered pediatric PVs. Statement of significanceHeart valve tissue engineering has the potential to transform treatment for children born with defective pulmonary valves by providing living replacement tissue that can grow with the child. The design of tissue engineered heart valves is best informed by native valve properties, but native pediatric pulmonary valves have not been fully described to date. Here, we provide comprehensive characterization of the planar biaxial tensile behaviour, extracellular matrix composition and organization, and valvular interstitial cell phenotypes of pulmonary valves from piglets as a model for the native human pediatric valve. Together, these findings provide standards that inform engineered heart valve design towards generation of biomimetic pediatric pulmonary valves.

Large animal model species in pluripotent stem cell therapy research and development for retinal diseases: a systematic review.

Retinal cell therapy modalities, in the category of advanced therapy medicinal products (ATMPs), are being developed to target several retinal diseases. Testing in large animal models (LAMs) is a crucial step in translating retinal ATMPs into clinical practice. However, challenges including budgetary and infrastructure constraints can hinder LAM research design and execution. Here, to facilitate the comparison of the various LAMs in pluripotent retinal cell therapy research, we aimed to systematically evaluate the species distribution, reported scientific utility, and methodology of a range of LAMs. A systematic search using the words retina, stem cell, transplantation, large animal, pig, rabbit, dog, and nonhuman primate was conducted in the PubMed, Embase, Science Direct and GoogleScholar databases in February 2023. We included 22 studies involving pluripotent stem cells (induced pluripotent stem cells or human embryonic stem cells) in LAMs, including non-human primates (NHP), pigs, dogs, and rabbits. Nearly half of the studies utilized wild-type animal models. In other studies, retinal degeneration features were simulated via laser, chemical, or genetic insult. Transplants were delivered subretinally, either as cell suspensions or pre-formed monolayers (with or without biodegradable scaffolding). The transplanted cells dose per eye varied widely (40,000 - 4,000,000 per dose). Cells were delivered via vitrectomy surgery in 15 studies and by an "ab externo" approach in one study. Structural outcomes were assessed using confocal scanning laser ophthalmoscopy imaging. Functional outcomes included multifocal electroretinogram and, in one case, a measure of visual acuity. Generally, cell suspension transplants exhibited low intraretinal incorporation, while monolayer transplants incorporated more efficiently. Immune responses posed challenges for allogeneic transplants, suggesting that autologous iPSC-derived transplants may be required to decrease the likelihood of rejection. The use of appropriate LAMs helps to advance the development of retinal ATMPs. The anatomical similarity of LAM and human eyes allows the implementation of clinically-relevant surgical techniques. While the FDA Modernization Act 2.0 has provided a framework to consider alternative methods including tissue-on-a-chip and human cell culture models for pharmacologic studies, LAM testing remains useful for cell and tissue replacement studies to inform the development of clinical trial protocols.

A comparison study on membrane fouling in A/O-MBR and A/A-MBR at different mixed liquor-suspended solids concentrations

ABSTRACT Membrane fouling leads to decreased membrane flux, increases the frequency of membrane tissue replacement and membrane cleaning, and increases the operating cost of membrane bioreactor. In this study, the pollutant removal effects, membrane fouling differences and microbial characteristics of anaerobic/aerobic MBR (A/O-MBR) and anaerobic/anoxic MBR (A/A-MBR) were investigated at different mixed liquor suspended solids (MLSS) concentrations. The results showed that the chemical cleaning cycle of membrane contamination was 12, 28, 44 h and 24, 40, 104 h, respectively, and the cycle was prolonged with the increase of MLSS concentration (from 6000 to 9000 mg L−1). A/O-MBR was 1.4–2.4 times the rate of membrane fouling of A/A-MBR. In irreversible resistance, extracellular polymer substances (EPS) were the most significant contributors to membrane fouling. EPS concentration in A/A-MBR (118.33, 73.75, 54.26 mg/gMLSS) was lower than that in A/O-MBR (171.68, 91.92, 62.33 mg/gMLSS). Therefore, increasing MLSS concentration could mitigate membrane fouling. 16S rRNA high-throughput sequencing demonstrated that filamentous bacteria was the primary reason for the membrane fouling difference. Filamentous bacteria were more likely to be attached to the surface of the membrane, causing membrane fouling. The abundance percentage of filamentous bacteria in A/A-MBR was smaller than that in A/O-MBR. In summary, The excellent performance of A/A-MBR in membrane fouling behaviour, resistance analysis, EPS and microorganisms proved that A/A-MBR is more promising than A/O-MBR in wastewater nitrogen and phosphorus removal. This study can provide a theoretical basis for the application of MBR in the field of sewage treatment.

Hydroxyapatite-Based Natural Biopolymer Composite for Tissue Regeneration.

Hydroxyapatite (HAp) polymer composites have gained significant attention due to their applications in bone regeneration and tooth implants. This review examines the synthesis, properties, and applications of Hap, highlighting various manufacturing methods, including wet, dry, hydrothermal, and sol-gel processes. The properties of HAp are influenced by precursor materials and are commonly obtained from natural calcium-rich sources like eggshells, seashells, and fish scales. Composite materials, such as cellulose-hydroxyapatite and gelatin-hydroxyapatite, exhibit promising strength and biocompatibility for bone and tissue replacement. Metallic implants and scaffolds enhance stability, including well-known titanium-based and stainless steel-based implants and ceramic body implants. Biopolymers, like chitosan and alginate, combined with Hap, offer chemical stability and strength for tissue engineering. Collagen, fibrin, and gelatin play crucial roles in mimicking natural bone composition. Various synthesis methods like sol-gel, hydrothermal, and solution casting produce HAp crystals, with potential applications in bone repair and regeneration. Additionally, the use of biowaste materials, like eggshells and snails or seashells, not only supports sustainable HAp production but also reduces environmental impact. This review emphasizes the significance of understanding the properties of calcium-phosphate (Ca-P) compounds and processing methods for scaffold generation, highlighting novel characteristics and mechanisms of biomaterials in bone healing. Comparative studies of these methods in specific applications underscore the versatility and potential of HAp composites in biomedical engineering. Overall, HAp composites offer promising solutions for improving patient outcomes in bone replacement and tissue engineering and advancing medical practices.

Effect of the Synergistic Interaction of Micro- and Nanostructures with Silver Ions on the Biocompatibility and Antimicrobial Properties of Ti-15Mo-2.5Ag.

Titanium and titanium alloys have the advantages of a low density and a close elastic modulus to natural bone, which can reduce the stress-shielding effect and become one of the first choices for human hard tissue replacement and repair. However, implant site infection is still one of the main reasons for implantation failure. In this paper, 2.5 wt % Ag element was added to Ti-15Mo to obtain a low modulus, and a surface anodization was applied to improve the surface biocompatibility. The elastic modulus, micromorphology, surface elemental valence, corrosion resistance, antimicrobial properties, and cytocompatibility were investigated by mechanical tests, scanning electron microscopy, X-ray photoelectron spectroscopy, electrochemical tests, inductively coupled plasma spectroscopy, plate counting method, and cellular tests. The experimental results showed that the anodized Ti-15Mo-2.5Ag sample exhibited an elastic modulus of 79 GPa, a strong corrosion resistance, a strong antimicrobial ability of ≥99.99%, and good biocompatibility. It was demonstrated that the formation of Ag2O on the surface and Ag ion release improved the antimicrobial properties and that the structural synergism of silver ions with micro- and nanostructures played an important role in promoting the early spreading of cells and improving the cytocompatibility.

Collagen Membrane as Artificial Dura Substitute: A Comprehensive In Vivo Study of Efficiency and Substitution Compared to Durepair

The dura mater is a barrier between the brain and the surrounding environment. Injuries to the dura can lead to serious complications, therefore, ensuring a hermetic closure of the dura is a primary task for a neurosurgeon. The aim of the study is to compare the effectiveness of applying the newly developed ViscollDURA collagen membrane (VDCM), with the commercially available Durepair (xenogeneic collagen) in animal model. A dural tear model was utilized in rats with membrane implantation using an application method. The sample size consisted of 24 rats. Group I underwent VDCM implantation, while Group II underwent Durepair implantation. Results were evaluated at 30, 60, and 90days. The study was assessed using magnetic resonance imaging, histology, electron scanning microscopy, and immunohistochemistry. The obtained results underwent statistical analysis. In the clinical presentation, there were no difference between groups. Histologically, Group 1 showed comparable results to Group 2. The integration process of the membrane statistically differed between the groups. In Group 1, neovascularization and tissue replacement showed better results than in Group 2. Magnetic resonance imaging differences were observed at later stages, with group 2 showing adhesion and brain deformation in the implantation area. Both membranes showed safety and compatibility. The collagen membrane produced under sterile conditions demonstrated better regeneration with minimal inflammatory reaction. The study suggests that VDCM exhibits biocompatibility comparable to Durepair, providing prospects for potential applications in neurosurgery.

(Invited) Fullerenes for Bio-Applications: The Way of Water

Nano-materials are emerging as important components for a series of bio-applications. In this context, carbon nanostructures such as graphene, carbon nanotubes and fullerenes have unique chemical and physical properties that make them attractive for such applications. Carbon nanomaterials have been used in tissue engineering, biosensing and drug delivery. They have also shown anti-microbial activity. They can be loaded with drugs for controlled local delivery. More importantly, the surface of carbon nanomaterials can be functionalised to enhance their biocompatibility by increasing their water-solubility.In this talk, I will present an update on our work in using fullerenes and their derivatives for developing bio-nanomaterials. I shall focus on the combination of carbon nanostructures and polymeric materials which can result in supramolecular hydrogels with interesting properties. Hydrogels are emerging as important materials in applications such as cellular scaffoldings in regenerative medicine/tissue engineering, tissue replacements, wound dressings, etc.I will present the synthesis of supramolecular hydrogels made from fullerenes of different sizes (C60, C84 and C90–92) that have been hydroxylated and functionalised with hydrophilic oligoethylene glycol chains. To the best of our knowledge, there have been no attempts made at incorporating higher fullerenes and their derivatives into such extended supramolecular structures, before now.I will also show possibilities for extending our approach to endohedral fullerenes such as N@C60. I will show how we can use advanced techniques including AFM to characterise the elasticity of the hydrogels formed. The ability to incorporate endohedral fullerenes in hydrogels may be important in extending the possibility for using these materials as sensors in vitro or even in vivo, exploiting the quantum properties of such molecular systems such as their extended electron and nuclear spin lifetimes.

Advanced Bioceramics: Properties, Fabrication and Applications

Bioceramics are engineered materials that achieve their applications in the medical field. Bioceramics are promising inorganic materials to create scaffolds for bone regeneration due to their desirable properties, such as biocompatibility, osteoconduction, and their similarity with bone composition. Bioceramics can operate as tissue replacement and can be used for coating metal implants to increase their biocompatibility. Bioceramics are classified into three types: bioinert ceramics, bioactive bioceramics, and biodegradable ceramics. There are different methods for the fabrication of bioceramics, they can be prepared by conventional powder processing methods or by some new unconventional methods. Bioceramics can be fabricated by a sintering process, which takes place through the hardening of the green bodies at a relatively high temperature lower than their melting point. Nowadays, microwave sintering is excellent in both heating efficiency, saving energy and time, and the concomitant processing cost. There are other methods used to obtain bioceramics; such as sol-gel, gas-foaming, gel-casting, and freeze-casting techniques. Recently, the CAD/CAM technique (computer-aided design/manufacture) was used in the fabrication of bioceramics and is applied in the dentistry field. The application of bioceramics connects to the repair of the skeletal system, which consists of joints, bones, and teeth, as well as both soft and hard tissues. Bioceramics can be used to replace parts of the cardiovascular system, especially heart valves.