Incorporation of Controlled Release Systems Improves the Functionality of Biodegradable 3D Printed Cardiovascular Implants.

New horizons in cardiovascular research are opened by using 3D printing for biodegradable implants. This additive manufacturing approach allows the design and fabrication of complex structures according to the patient's imaging data in an accurate, reproducible, cost-effective, and quick manner. Acellular cardiovascular implants produced from biodegradable materials have the potential to provide enough support for in situ tissue regeneration while gradually being replaced by neo-autologous tissue. Subsequently, they have the potential to prevent long-term complications. In this Review, we discuss the current status of 3D printing applications in the development of biodegradable cardiovascular implants with a focus on design, biomaterial selection, fabrication methods, and advantages of implantable controlled release systems. Moreover, we delve into the intricate challenges that accompany the clinical translation of these groundbreaking innovations, presenting a glimpse of potential solutions poised to enable the realization of these technologies in the realm of cardiovascular medicine.

Recent advances in 3D bioprinted tumor models for personalized medicine.

Cancerous tumors are among the most fatal diseases worldwide, claiming nearly 10 million lives in 2020. Due to their complex and dynamic nature, modeling tumors accurately is a challenging task. Current models suffer from inadequate translation between in vitro and in vivo results, primarily due to the isotropic nature of tumors and their microenvironment's relationship. To address these limitations, hydrogel-based 3D bioprinting is emerging as a promising approach to mimic cancer development and behavior. It provides precise control over individual elements' size and distribution within the cancer microenvironment and enables the use of patient-derived tumor cells, rather than commercial lines. Consequently, hydrogel bioprinting is expected to become a state-of-the-art technique for cancer research. This manuscript presents an overview of cancer statistics, current modeling methods, and their limitations. Additionally, we highlight the significance of bioprinting, its applications in cancer modeling, and the importance of hydrogel selection. We further explore the current state of creating models for the five deadliest cancers using 3D bioprinting. Finally, we discuss current trends and future perspectives on the clinical use of cancer modeling using hydrogel bioprinting.

Polysaccharide-based biomaterials in a journey from 3D to 4D printing.

3D printing is a state-of-the-art technology for the fabrication of biomaterials with myriad applications in translational medicine. After stimuli-responsive properties were introduced to 3D printing (known as 4D printing), intelligent biomaterials with shape configuration time-dependent character have been developed. Polysaccharides are biodegradable polymers sensitive to several physical, chemical, and biological stimuli, suited for 3D and 4D printing. On the other hand, engineering of mechanical strength and printability of polysaccharide-based scaffolds along with their aneural, avascular, and poor metabolic characteristics need to be optimized varying printing parameters. Multiple disciplines such as biomedicine, chemistry, materials, and computer sciences should be integrated to achieve multipurpose printable biomaterials. In this work, 3D and 4D printing technologies are briefly compared, summarizing the literature on biomaterials engineering though printing techniques, and highlighting different challenges associated with 3D/4D printing, as well as the role of polysaccharides in the technological shift from 3D to 4D printing for translational medicine.

Human Olfactory Ecto-mesenchymal Stem Cells Displaying Schwann-cell-like Phenotypes and Promoting Neurite Outgrowth in Vitro.

Introduction: Strategies of Schwann cell (SC) transplantation for regeneration of peripheral nerve injury involve many limitations. Stem cells can be used as alternative cell source for differentiation into Schwann cells. Given the high potential of neural crest-derived stem cells for the generation of multiple cell lineages, in this research, we considered whether olfactory ectomesenchymal stem cells (OE-MSCs) derived from neural crest can spontaneously differentiate into SC lineage. Methods: OE-MSCs were isolated from human nasal mucosa and characterized by the mesenchymal and neural crest markers. The cells were cultured in glial growth factors-free medium and further investigated in terms of the phenotypic and functional properties. Results: Immunocytochemical staining and real-time PCR analysis indicated that the cultured OE-MSCs expressed SCs markers, SOX10, p75, S100, GFAP and MBP, differentiation indicative. It was found that the cells could secrete neurotrophic factors, including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). Furthermore, after co-cultured with PC12, the mean neurite length was enhanced by OE-MSCs. Conclusion: The findings indicated that OE-MSCs could be differentiated spontaneously into SC-like phenotypes, suggesting their applications for transplantation in peripheral nerve injuries.

Nanostructured bioactive glasses: A bird's eye view on cancer therapy.

Bioactive glasses (BGs) arewell known for their successful applications in tissue engineering and regenerative medicine. Recent experimental studies have shown their potential usability in oncology, either alone or in combination with other biocompatible materials, such as biopolymers. Direct contact with BG particles has been found to cause toxicity and death in specific cancer cells (bone-derived neoplastic stromal cells) in vitro. Nanostructured BGs (NBGs) can be doped with anticancer elements, such as gallium, to enhance their toxic effects against tumor cells. However, the molecular mechanisms and intracellular targets for anticancer compositions of NBGs require further clarification. NBGs have been successfully evaluated for use in various well-established cancer treatment strategies, including cancer hyperthermia, phototherapy, and anticancer drug delivery. Existing results indicate that NBGs not only enhance cancer cell death, but can also participate in the regeneration of lost healthy tissues. However, the application of NBGs in oncology is still in its early stages, and numerous unanswered questions must be addressed. For example, the impact of the composition, biodegradation, size, and morphology of NBGs on their anticancer efficacy should be defined for each type of cancer and treatment strategy. Moreover, it should be more clearly assessed whether NBGs can shrink tumors, slow/stop cancer progression, or cure cancer completely. In this regard, the use of computational studies (in silico methods) is highly recommended to design the most effective glass formulations for cancer therapy approaches and to predict, to some extent, the relevant properties, efficacy, and outcomes. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Tissue-engineered small-diameter vascular grafts containing novel copper-doped bioactive glass biomaterials to promote angiogenic activity and endothelial regeneration.

Small-diameter vascular grafts frequently fail because of obstruction and infection. Despite the wide range of commercially available vascular grafts, the anatomical uniqueness of defect sites demands patient-specific designs. This study aims to increase the success rate of implantation by fabricating bilayer vascular grafts containing bioactive glasses (BGs) and modifying their composition by removing hemostatic ions to make them blood-compatible and to enhance their antibacterial and angiogenesis properties. The porous vascular graft tubes were 3D printed using polycaprolactone, polyglycerol sebacate, and the modified BGs. The polycaprolactone sheath was then wrapped around the 3D-printed layer using the electrospinning technique to prevent blood leakage. The results demonstrated that the incorporation of modified BGs into the polymeric matrix not only improved the mechanical properties of the vascular graft but also significantly enhanced its antibacterial activity against both gram-negative and gram-positive strains. In addition, no hemolysis or platelet activity was detected after incorporating modified BGs into the vascular grafts. Copper-releasing vascular grafts significantly enhanced endothelial cell proliferation, motility, and VEGF secretion. Additionally, In vivo angiogenesis (CD31 immunofluorescent staining) and gene expression experiments showed that copper-releasing vascular grafts considerably promoted the formation of new blood vessels, low-grade inflammation (decreased expression of IL-1ß and TNF-α), and high-level angiogenesis (increased expression of angiogenic growth factors including VEGF, PDGF-BB, and HEBGF). These observations indicate that the use of BGs with suitable compositional modifications in vascular grafts may promote the clinical success of patient-specific vascular prostheses by accelerating tissue regeneration without any coagulation problems.

Fabrication of a microfluidic device for probiotic drug's dosage screening: Precision Medicine for Breast Cancer Treatment.

Breast cancer is the most common cancer in women; it has been affecting the lives of millions each year globally and microfluidic devices seem to be a promising method for the future advancements in this field. This research uses a dynamic cell culture condition in a microfluidic concentration gradient device, helping us to assess breast anticancer activities of probiotic strains against MCF-7 cells. It has been shown that MCF-7 cells could grow and proliferate for at least 24 h; however, a specific concentration of probiotic supernatant could induce more cell death signaling population after 48 h. One of our key findings was that our evaluated optimum dose (7.8 mg/L) was less than the conventional static cell culture treatment dose (12 mg/L). To determine the most effective dose over time and the percentage of apoptosis versus necrosis, flowcytometric assessment was performed. Exposing the MCF-7 cells to probiotic supernatant after 6, 24 and 48 h, confirmed that the apoptotic and necrotic cell death signaling were concentration and time dependent. We have shown a case that these types of microfluidics platforms performing dynamic cell culture could be beneficial in personalized medicine and cancer therapy.

Fabrication and characterization of bilayer scaffolds made of decellularized dermis/nanofibrous collagen for healing of full-thickness wounds.

Skin tissue engineering has progressed from simple wound dressings to biocompatible materials with desired physico-chemical properties that can deliver regenerative biomolecules. This study describes using a novel biomimetic hybrid scaffold of decellularized dermis/collagen fibers that can continuously deliver stromal cell-derived factor-1 alpha (SDF-1α) for skin regeneration. In diabetic rat models, the idea that sustained SDF-1α infusion could increase the recruitment of CXCR4-positive cells at the injury site and improve wound regeneration was investigated. The morphology of the scaffold, its biocompatibility, and the kinetics of SDF-1 release were all assessed. SDF-1α was successfully incorporated into collagen nanofibers, resulting in a 200-h continuous release profile. The microscopic observations exhibited that cells are attached and proliferated on proposed scaffolds. As evaluated by in vivo study and histological examination, fabricated scaffold with SDF-1α release capacity exhibited a remarkably more robust ability to accelerate wound regeneration than the control group. Besides, the SDF-1α-loaded scaffold demonstrated functional effects on the proliferation and recruitment of CD31 and CXCR4-positive cells in the wound bed. Additionally, no adverse effects such as hyperplasia or scarring were found during the treatment period. It may be concluded that the fabricated hybrid scaffold based on natural polymer opens up a new option for topical administration of bioactive molecules. We believe the SDF-1α-loaded hybrid scaffold has promise for skin tissue engineering.

Nanoscale biomaterials for terahertz imaging: A non-invasive approach for early cancer detection.

Terahertz (THz) technology is developing a non-invasive imaging system for biosensing and clinical diagnosis. THz medical imaging mainly benefits from great sensitivity in detecting changes in water content and structural variations in diseased cells versus normal tissues. Compared to healthy tissues, cancerous tumors contain a higher level of water molecules and show structural changes, resulting in different THz absorption. Here we described the principle of THz imaging and advancement in the field of translational biomedicine and early detection of pathologic tissue, with a particular focus on oncology. In addition, although the main forte of THz imaging relies on detecting differences in water content to distinguish the exact margin of tumor, THz displays limited contrast in living tissue for in-vivo clinical imaging. In the last few years, nanotechnology has attracted attention to aid THz medical imaging and various nanoparticles have been investigated as contrast enhancements to improve the accuracy, sensitivity, and specificity of THz images. Most of these multimodal contrast agents take advantage of the temperature-dependent of THz spectrum to the conformational variation of the water molecule. We discuss advances in developing THz contrast agents to accelerate the advancement of non-invasive THz imaging with improved sensitivity and specificity for translational clinical oncology.

Additive manufacturing of bioactive glass biomaterials.

Tissue engineering (TE) and regenerative medicine have held great promises for the repair and regeneration of damaged tissues and organs. Additive manufacturing has recently appeared as a versatile technology in TE strategies that enables the production of objects through layered printing. By applying 3D printing and bioprinting, it is now possible to make tissue-engineered constructs according to desired thickness, shape, and size that resemble the native structure of lost tissues. Up to now, several organic and inorganic materials were used as raw materials for 3D printing; bioactive glasses (BGs) are among the most hopeful substances regarding their excellent properties (e.g., bioactivity and biocompatibility). In addition, the reported studies have confirmed that BG-reinforced constructs can improve osteogenic, angiogenic, and antibacterial activities. This review aims to provide an up-to-date report on the development of BG-containing raw biomaterials that are currently being employed for the fabrication of 3D printed scaffolds used in tissue regeneration applications with a focus on their advantages and remaining challenges.

Nanotechnology and quantum science enabled advances in neurological medical applications: diagnostics and treatments.

The beginning of the twenty-first century saw advancements in all areas of life, including medicine and nanotechnology. This review will look at the most recent advances in nanomaterials for diagnostics and treatments. The emphasis is on the application of nanofibers, nanosensors, and quantum dots (QDs) in medication delivery, neuron regeneration, chemical detection, and microelectrode probes. The manufacture of implantable nanofibers and nanosensors based on QDs, and their application-specific features impacting the interface with targeted brain cells were described. The collaborative efforts have helped us to understand the potential of nanostructured materials in fabrication to overcome the limits of micro and bulk materials in treatments and diagnostics. These advancements will eventually lead to using nanostructures, including nanofibers and nanosensors, in high throughput cutting-edge applications. Only when extensive safety investigations have been completed may the use of nanomaterials on an industrial basis be viable. This review discusses the recent advances in the usage of nanostructures and nanoparticles (NPs) for diagnostics and treatments, with a special focus on nanofibers, nanosensors, and quantum dots (QDs) applications in drug delivery, nerve regeneration, chemical detection, and microelectrode probes.

Mussel-inspired biomaterials: From chemistry to clinic.

After several billions of years, nature still makes decisions on its own to identify, develop, and direct the most effective material for phenomena/challenges faced. Likewise, and inspired by the nature, we learned how to take steps in developing new technologies and materials innovations. Wet and strong adhesion by Mytilidae mussels (among which Mytilus edulis-blue mussel and Mytilus californianus-California mussel are the most well-known species) has been an inspiration in developing advanced adhesives for the moist condition. The wet adhesion phenomenon is significant in designing tissue adhesives and surgical sealants. However, a deep understanding of engaged chemical moieties, microenvironmental conditions of secreted proteins, and other contributing mechanisms for outstanding wet adhesion mussels are essential for the optimal design of wet glues. In this review, all aspects of wet adhesion of Mytilidae mussels, as well as different strategies needed for designing and fabricating wet adhesives are discussed from a chemistry point of view. Developed muscle-inspired chemistry is a versatile technique when designing not only wet adhesive, but also, in several more applications, especially in the bioengineering area. The applications of muscle-inspired biomaterials in various medical applications are summarized for future developments in the field.

Engineered hyaluronic acid-decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancer.

Targeted drug delivery systems using nanocarriers offer a versatile platform for breast cancer treatment; however, a robust, CD44-targeted niosomal formulation has not been developed and deeply studied (both in vitro and in vivo) yet. Here, an optimized system of epirubicin (Epi)-loaded niosomal nanoparticles (Nio) coated with hyaluronic acid (HA) has been engineered for targeting breast cancer cells. The nanoformulation was first optimized (based on size, polydispersity index, and entrapment efficiency); then, we characterized the morphology, stability, and release behavior of the nanoparticles. Epirubicin release from the HA-coated system (Epi-Nio-HA) showed a 21% (acidic buffer) and 20% (neutral buffer) reduction in comparison with the non-coated group (Epi-Nio). The cytotoxicity and apoptosis results of 4T1 and SkBr3 cells showed an approximately 2-fold increase in the Epi-Nio-HA system over Epi-Nio and free epirubicin, which confirms the superiority of the engineered nanocarriers. Moreover, real-time PCR data demonstrated the down-regulation of the MMP-2, MMP-9, cyclin D, and cyclin E genes expression while caspase-3 and caspase-9 gene expression were up-regulated. Confocal microscopy and flow cytometry studies uncovered the cellular uptake mechanism of the Epi-Nio-HA system, which was CD44-mediated. Furthermore, in vivo studies indicated Epi-Nio-HA decreased mice breast tumor volume by 28% (compared to epirubicin) without side effects on the liver and kidney. Conclusively, our results indicated that the HA-functionalized niosomes provide a promising nanoplatform for efficient and targeted delivery of epirubicin to potentially treat breast cancer.

Smart biomaterials: From 3D printing to 4D bioprinting.

This century is blessed with enhanced medical facilities on the grounds of the development of smart biomaterials. The rise of the four-dimensional (4D) bioprinting technology is a shining example. Using inert biomaterials as the bioinks for the three-dimensional (3D) printing process, static objects that might not be able to mimic the dynamic nature of tissues would be fabricated; by contrast, 4D bioprinting can be used for the fabrication of stimuli-responsive cell-laden structures that can evolve with time and enable engineered tissues to undergo morphological changes in a pre-planned way. For all the aptitude of 4D bioprinting technology in tissue engineering, it is imperative to select suitable stimuli-responsive biomaterials with cell-supporting functionalities and responsiveness; as a result, in this article, recent advances and challenges in smart biomaterials for 4D bioprinting are briefly discussed. An overview perspective concerning the latest developments in 4D-bioprinting is also provided.