Biomaterials and biosystems最新文献

There is a deep interest in developing new Ni-free Ti-based alloys to replace 316 L stainless steel and Co-Cr alloys for endovascular stent application, mainly because the release of Ni can generate toxicity and allergenicity. Interactions of Ti alloy biomaterials with bone cells and tissues have been widely investigated and reported, while interactions with vascular cells and tissues, such as endothelial cells (ECs) and smooth muscle cells (SMCs), are scarce. Therefore, this study focused on the relationship among the surface finishing features, corrosion behavior and in vitro biological performances regarding human ECs, SMCs and blood of a newly developed Ti-8Mo-2Fe (TMF) alloy, specifically designed for balloon-expandable stent applications. The alloy performances were compared to those of 316 L and pure Ti, prepared with the same surface finishing techniques, which are mechanical polishing and electropolishing. Surface properties were investigated by scanning electron microscopy (SEM), atomic force microscopy (AFM), contact angle (CA) and x-ray photoelectron spectroscopy (XPS). The corrosion behavior was assessed with potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS) tests in phosphate buffered saline (PBS) solution. No significant differences were observed regarding the corrosion rate measured with PDP analyses, which was of the order of 2 × 10⁻⁴ mm/y for all the studied materials. Moreover, similarly to pure Ti, TMF exhibited an advantage over 316 L for biomedical applications, namely remarkable resistance to pitting corrosion up to high potentials. The results evidenced a good cytocompatibility and hemocompatibility, making this group of alloy a potential candidate for cardiovascular implants. In fact, both ECs and SMCs proliferated on TMF surfaces showing a 7-day viability similar to that of pure Ti. Regarding hemocompatibility, TMF did not cause hemolysis, and blood coagulation was delayed on its surface in comparison to pure Ti. When compared to 316 L, TMF showed similar hemocompatibility.

Thoracic aortic aneurysms and dissections (TAADs) involve dilation of the aortic wall that can lead to tearing or rupture. Progressive extracellular matrix (ECM) degradation is common in TAAD, regardless of the underlying cause. TAAD treatments typically target cellular signaling pathways, rather than the ECM itself, due to the complex assembly process and long half-life of ECM proteins. Compounds that stabilize the ECM are proposed as an alternative TAAD therapy that addresses the underlying cause of aortic wall failure, namely compromised structural integrity. Compounds are discussed that revisit historical approaches to maintain and preserve structural integrity of biological tissues.

The viral infection spreads with the assistance of a host. Traditional antiviral therapies cannot provide long-term immunity against emerging and drug-resistant viral infections. Immunotherapy has evolved as an efficient approach for disease prevention and treatment, which include cancer, infections, inflammatory, and immune disorders. Immunomodulatory nanosystems can dramatically enhance therapeutic outcomes by combating many therapeutic challenges, such as poor immune stimulation and off-target adverse effects. Recently, immunomodulatory nanosystems have emerged as a potent antiviral strategy to intercept viral infections effectively. This review introduces major viral infections with their primary symptoms, route of transmission & targeted organ, and different stages of the viral life cycle with respective traditional blockers. The IMNs have an exceptional capacity for precisely modulating the immune system for therapeutic applications. The nano sized immunomodulatory systems permit the immune cells to interact with infectious agents enhancing lymphatic drainage and endocytosis by the over-reactive immune cells in the infected areas. Immune cells that can be modulated upon viral infection via various immunomodulatory nanosystems have been discussed. Advancement in theranostics can yield an accurate diagnosis, adequate treatment, and real-time screening of viral infections. Nanosystem-based drug delivery can continue to thrive in diagnosing, treating, and preventing viral infections. The curative medicine for remerging and drug-resistant viruses remains challenging, though certain systems have expanded our perception and initiated a new research domain in antiviral treatments.

Tracheal replacement using tissue engineering technologies offers great potential to improve previously intractable clinical interventions, and interest in this area has increased in recent years. Many engineered airway constructs currently rely on decellularized native tracheas to serve as the scaffold for tissue repair. Yet, mechanical failure leading to airway narrowing and collapse remains a major cause of morbidity and mortality following clinical implantation of decellularized tracheal grafts. To understand better the factors contributing to mechanical failure in vivo, we characterized the histo-mechanical properties of tracheas following two different decellularization protocols, including one that has been used clinically. All decellularized tracheas deviated from native mechanical behavior, which may provide insights into observed in vivo graft failures. We further analyzed protein content by western blot and analyzed microstructure by histological staining and found that the specific method of decellularization resulted in significant differences in the depletion of proteoglycans and degradation of collagens I, II, III, and elastin. Taken together, this work demonstrates that the heterogeneous architecture and mechanical behavior of the trachea is severely compromised by decellularization. Such structural deterioration may contribute to graft failure clinically and limit the potential of decellularized native tracheas as viable long-term orthotopic airway replacements.

Physiological inflammation has been shown to promote bone regeneration; however, prolonged inflammation impedes the osteogenesis and bone repair process. To overcome the latter we aimed to develop a dual drug delivering nanofibrous scaffold to promote osteogenic differentiation of mesenchymal stromal cells (MSCs) and modulate the pro-inflammatory response of macrophages. The polycaprolactone (PCL)-collagen nanofibrous delivery system incorporating dexamethasone and simvastatin was fabricated by electrospinning process. The morphological analysis and mRNA, as well as protein expression of proinflammatory and anti-inflammatory cytokines in human monocytes (U937 cells), demonstrated the immunocompatibility effect of dual drug-releasing nanofibrous scaffolds. Nitric oxide estimation also demonstrated the anti-inflammatory effect of dual drug releasing scaffolds. The scaffolds demonstrated the osteogenic differentiation of adipose-derived MSCs by enhancing the alkaline phosphatase (ALP) activity and mineral deposition after 17 days of cell culture. The increased expression of Runt-related transcription factor-2 (RUNX-2) and osteocalcin at mRNA and protein levels supported the osteogenic potential of dual drug-loaded fibrous scaffolds. Hence, the results indicate that our fabricated nanofibrous scaffolds exhibit immunomodulatory properties and could be employed for bone regeneration applications after further in-vivo validation.

Cartilage has poor regenerative capacity and thus damage to the joint surfaces presents a major clinical challenge. Recent research has focussed on the development of tissue-engineered and cell-based approaches for the treatment of cartilage and osteochondral injuries, with current clinically available cell-based approaches including autologous chondrocyte implantation and matrix-assisted autologous chondrocyte implantation. However, these approaches have significant disadvantages due to the requirement for a two-stage surgical procedure and an in vitro chondrocyte expansion phase which increases logistical challenges, hospital times and costs. In this study, we hypothesized that seeding biomimetic tri-layered scaffolds, with proven regenerative potential, with chondrocyte/infrapatellar fat pad stromal cell co-cultures would improve their regenerative capacity compared to scaffolds implanted cell-free. Rapid cell isolation techniques, without the requirement for long term in vitro culture, were utilised to achieve co-cultures of chondrocytes and stromal cells and thus overcome the limitations of existing cell-based techniques. Cell-free and cell-seeded scaffolds were implanted in osteochondral defects, created within the femoral condyle and trochlear ridge, in a translational large animal goat model. While analysis showed trends towards delayed subchondral bone healing in the cell-seeded scaffold group, by the 12 month timepoint the cell-free and cell-seeded groups yield cartilage and bone tissue with comparable quality and quantity. The results of the study reinforce the potential of the biomimetic tri-layered scaffold to repair joint defects but failed to demonstrate a clear benefit from the addition of the CC/FPMSC co-culture to this scaffold. Taking into consideration the additional cost and complexity associated with the cell-seeded scaffold approach, this study demonstrates that the treatment of osteochondral defects using cell-free tri-layered scaffolds may represent a more prudent clinical approach.

One of the major aims of bio-engineering tissue equivalents in vitro is to create physiologically relevant culture conditions to accurately recreate the cellular microenvironment. This often includes incorporation of factors such as the extracellular matrix, co-culture of multiple cell types and three-dimensional culture techniques. These advanced techniques can recapitulate some of the properties of tissue in vivo, however fluid flow is a key aspect that is often absent. Fluid flow can be introduced into cell and tissue culture using bioreactors, which are becoming increasingly common as we seek to produce increasingly accurate tissue models. Bespoke technology is continuously being developed to tailor systems for specific applications and to allow compatibility with a range of culture techniques. For effective perfusion of a tissue culture many parameters can be controlled, ranging from impacts of the fluid flow such as increased shear stress and mass transport, to potentially unwanted side effects such as temperature fluctuations. A thorough understanding of these properties and their implications on the culture model can aid with a more accurate interpretation of results. Improved and more complete characterisation of bioreactor properties will also lead to greater accuracy when reporting culture conditions in protocols, aiding experimental reproducibility, and allowing more precise comparison of results between different systems. In this review we provide an analysis of the different factors involved in the development of benchtop flow bioreactors and their potential biological impacts across a range of applications.

The culture microenvironment has been demonstrated to regulate stem cell fate and to be a crucial aspect for quality-controlled stem cell maintenance and differentiation to a specific lineage. In this context, extracellular matrix (ECM) proteins are particularly important to mediate the interactions between the cells and the culture substrate. Human induced pluripotent stem cells (hiPSCs) are usually cultured as anchorage-dependent cells and require adhesion to an ECM substrate to support their survival and proliferation in vitro. Matrigel, a common substrate for hiPSC culture is a complex and undefined mixture of ECM proteins which are expensive and not well suited to clinical application. Decellularized cell-derived ECM has been shown to be a promising alternative to the common protein coatings used in stem cell culture. However, very few studies have used this approach as a niche for neural differentiation of hiPSCs.

Here, we developed a new stem cell culture system based on decellularized cell-derived ECM from neural progenitor cells (NPCs) for expansion and neural differentiation of hiPSCs, as an alternative to Matrigel and poly-l-ornithine/laminin-coated well plates. Interestingly, hiPSCs were able to grow and maintain their pluripotency when cultured on decellularized ECM from NPCs (NPC ECM). Furthermore, NPC ECM enhanced the neural differentiation of hiPSCs compared to poly-l-ornithine/laminin-coated wells, which are used in most neural differentiation protocols, presenting a statistically significant enhancement of neural gene expression markers, such as βIII-Tubulin and MAP2.

Taken together, our results demonstrate that NPC ECM provides a functional microenvironment, mimicking the neural niche, which may have interesting future applications for the development of new strategies in neural stem cell research.

Metal-organic frameworks (MOFs) are an emerging group of nanomaterials for successful biomedical applications in gene therapy. The most commonly biocompatible MOFs are zinc-based ZIFs, zirconium-based UiOs, and iron-based MILs. However, despite increasing applications, a comparative study to underscore the critical factors for determining effective gene delivery by such MOFs is lacking. Herein, we evaluate the potential of UiO-66 and MIL-88B and ZIF-8 for gene therapeutics delivery; revealing the comparative importance of ZIF-8. Cytotoxicity assays proved insufficient for selecting the ideal gene delivery MOF vehicle. Synthesis conditions such as ability of the MOF scaffold to envelop the gene during in-situ synthesis, post-treatment such as washing, and gene loading efficiency proved to be the critical factors in determining the favourable MOF from the material selection perspective. Rapid in-situ synthesis under physiological conditions, successful gene loading, and low concentration requirements favour ZIF MOFs as gene delivery vehicles. Impact on cellular physiology, metabolism, and architecture revealed neutrality of the delivery system; and relative effects on pro-inflammatory and anti-inflammatory cytokines suggest immunomodulatory impact.

Candida albicans and methicillin-resistant Staphylococcus aureus (MRSA) synergize in cross-kingdom biofilms to increase the risk of mortality and morbidity due to high resistance to immune and antimicrobial defenses. Biomedical devices and implants made with titanium are vulnerable to infections that may demand their surgical removal from the infected sites. Graphene nanocoating (GN) has promising anti-adhesive properties against C. albicans. Thus, we hypothesized that GN could prevent fungal yeast-to-hyphal switching and the development of cross-kingdom biofilms. Herein, titanium (Control) was coated with high-quality GN (coverage > 99%). Thereafter, mixed-species biofilms (C. albicans combined with S. aureus or MRSA) were allowed to develop on GN and Control. There were significant reductions in the number of viable cells, metabolic activity, and biofilm biomass on GN compared with the Control (CFU counting, XTT reduction, and crystal violet assays). Also, biofilms on GN were sparse and fragmented, whereas the Control presented several bacterial cells co-aggregating with intertwined hyphal elements (confocal and scanning electronic microscopy). Finally, GN did not induce hemolysis, an essential characteristic for blood-contacting biomaterials and devices. Thus, GN significantly inhibited the formation and maturation of deadly cross-kingdom biofilms, which can be advantageous to avoid infection and surgical removal of infected devices.