Biomaterials are increasingly used as implants in the body, but they often elicit tissue reactions due to the immune system recognizing them as foreign bodies. These reactions typically involve the activation of innate immunity and the initiation of an inflammatory response, which can persist as chronic inflammation, causing implant failure. To reduce these risks, various strategies have been developed to modify the material composition, surface characteristics, or mechanical properties of biomaterials. Moreover, bioactive materials have emerged as a new class of biomaterials that can induce desirable tissue responses and form a strong bond between the implant and the host tissue. In recent years, different immunomodulatory strategies have been incorporated into biomaterials as drug delivery systems. Furthermore, more advanced molecule and cell-based immunomodulators have been developed and integrated with biomaterials. These emerging strategies will enable better control of the immune response to biomaterials and improve the function and longevity of implants and, ultimately, the outcome of biomaterial-based therapies.

Wounds are regarded as disruptions in the integrity of human skin tissues, and the process of wound healing is often characterized as protracted and complex, primarily due to the potential infection or inflammation caused by microorganisms. The quest for innovative solutions that accelerate wound healing while prioritizing patient safety and comfort has emerged as a focal point. Within this pursuit, silkworm silk fibroin-a natural polymer extracted from silk cocoons-exhibits a distinctive combination of properties including biocompatibility, biodegradability, superior mechanical strength, water absorption, and low immunogenicity, which align closely with the demands of contemporary wound care. Its remarkable biocompatibility facilitates seamless integration with host tissues, thereby minimizing the risk of rejection or adverse reactions. Furthermore, its intrinsic degradability permits controlled release of therapeutic agents, promoting an optimal microenvironment conducive to healing. This review investigates the multifaceted potential of silk fibroin specifically as a wound dressing material and examines the intricate nuances associated with its application in hydrogels for wound healing, aiming to furnish a thorough overview for both researchers and clinicians. By scrutinizing underlying mechanisms, current applications, and prospective directions, we aspire to cultivate new insights and inspire innovative strategies within this rapidly evolving field.

Diabetic infected bone defect remains a great challenge in clinical practice, with delayed healing characterized by bacterial infection and cellular disfunction caused by oxidative stress. Hence, a novel self-healing multifunctional Ag@PEG-4OI/EXO hydrogel is introduced for improving healing of diabetic infected bone defect. 4-octyl itaconate, a derivative of the metabolite itaconate, has been proved that which performs antioxidant and mitochondria-protected properties. Simultaneously, the Ag+ that performed as cross-linking agent binds 4-arm-PEG-SH to form anti-bacterial hydrogel to deliver the bioactive molecule. The released of 4OI is confirmed that it can alleviate excessive ROS damage to cells and protect mitochondrial functions according to Keap1-Nrf2 pathway, synergistically promoting neurovascularization and osteogenic differentiation with EXO (from repair Schwann cells). In vivo, the Ag@PEG-4OI/EXO hydrogel also shows ideal antibacterial property and ameliorate the microenvironment of cells, finally promoting regeneration of CGRP+ nerve fibers and bone healing. In vivo and in vitro studies demonstrate that the improvement functions of cells with the use of the Ag@PEG-4OI/EXO hydrogel, presenting a viable strategy for diabetic infected bone defect.

Tissue engineering (TE) aims to provide personalized solutions for tissue loss caused by trauma, tumors, or congenital defects. While traditional methods like autologous and homologous tissue transplants face challenges such as donor shortages and risk of donor site morbidity, TE provides a viable alternative using scaffolds, cells, and biologically active molecules. Textiles represent a promising scaffold option for both in-vitro and in-situ TE applications. Textile engineering is a broad field and can be divided into fiber-based textiles and yarn-based textiles. In fiber-based textiles the textile fabric is produced in the same step as the fibers (e.g. non-wovens, electrospun mats and 3D-printed). For yarn-based textiles, yarns are produced from fibers or filaments first and then, a textile fabric is produced (e.g. woven, weft-knitted, warp-knitted and braided fabrics). The selection of textile scaffold technology depends on the target tissue, mechanical requirements, and fabrication methods, with each approach offering distinct advantages. Braided scaffolds, with their high tensile strength, are ideal for load-bearing tissues like tendons and ligaments, while their ability to form stable hollow lumens makes them suitable for vascular applications. Weaving, weft-, and warp-knitting provide tunable structural properties, with warp-knitting offering the greatest design flexibility. Spacer fabrics enable complex 3D architecture, benefiting applications such as skin grafts and multilayered tissues. Electrospinning, though highly effective in mimicking the ECM, is structurally limited. The complex interactions between materials, fiber properties, and textile technologies allows for scaffolds with a wide range of morphological and mechanical characteristics (e.g., tensile strength of woven textiles ranging from 0.64 to 180.4 N/mm2). With in-depth knowledge, textiles can be tailored to obtain specific mechanical properties as accurately as possible and aid the formation of functional tissue. However, as textile structures inherently differ from biological tissues, careful optimization is required to enhance cell behavior, mechanical performance, and clinical applicability. This review is intended for TE experts interested in using textiles as scaffolds and provides a detailed analysis of the available options, their characteristics and known applications. For this, first the major fiber formation methods are introduced, then subsequent used automated textile technologies are presented, highlighting their strengths and limitations. Finally, we analyze how these textile and fiber structures are utilized in TE, organized by the use of textiles in TE across major organ systems, including the nervous, skin, cardiovascular, respiratory, urinary, digestive, and musculoskeletal systems.

Spinal cord injury (SCI), the most serious disease affecting the central nervous system (CNS), is one of contemporary medicine's most difficult challenges, causing patients to suffer physically, emotionally, and socially. However, due to recent advances in medical science and biomaterials, graphene-based materials (GBMs) have tremendous potential in SCI therapy due to their wonderful and valuable properties, such as physicochemical properties, extraordinary electrical conductivity, distinct morphology, and high mechanical strength. This review discusses SCI pathology and GBM characteristics, as well as recent in vitro and in vivo findings on graphenic scaffolds, electrodes, and injectable achievements for SCI improvement using neuroprotective and neuroregenerative techniques to improve neural structural and functional repair. Additionally, it suggests possible ideas and desirable products for graphene-based technological advances, intending to reach therapeutic importance for SCI.

Although neural tissue engineering holds great therapeutic potential for multiple clinical applications, one important challenge is the development of scaffolds that provide cues required for neural tissue development. To achieve this, biomaterial systems can be leveraged to present appropriate biological, mechanical, topographical and electrical cues that could direct cell fate. In this study, a multi-layered electrode construct was engineered to be used as a platform for 3D cell encapsulation for in vitro applications. The first layer is a conductive hydrogel coating, that improves electrical conductivity from the underlying platinum electrode. The second layer is a biosynthetic hydrogel, specifically tailored to support neural development. This layered electrode construct was electrochemically characterised, and a numerical model was applied to study electrical stimuli reaching the biosynthetic hydrogel layer. The construct was shown to effectively support the growth and proliferation of encapsulated astrocytes within the biosynthetic layer, while the numerical model will enable computational experimentation for benchmarking and study validation. This highly versatile system represents a robust tool to study the influence of electrical stimuli on neural fate, as well as investigating the development of biohybrid interfaces in vitro.

Neurodegenerative disorders present significant therapeutic challenges, particularly due to the complex nature of drug delivery to the central nervous system. This review investigates the applications of various biopolymers in neuroprotection and their potential role in treating neurodegeneration. We present a critical analysis of natural and synthetic biopolymers, focusing primarily on chitosan, fish collagen/gelatin, and alginate as key therapeutic agents. The review examines the fundamental mechanisms of brain development and neurodegeneration, establishing a framework for understanding how these biopolymers interact with neural tissues. By analyzing recent experimental studies, we evaluate the effectiveness of different biopolymer-based delivery systems in crossing the blood-brain barrier and their subsequent neuroprotective effects. Additionally, promising materials, including lignin, poly lactic-co-glycolic acid, and glucose-modified bovine serum albumin/procyanidin complexes, are briefly explored to provide a comprehensive overview of current developments in the field. Our analysis reveals that biopolymer-based approaches offer unique advantages in both neuroprotection and drug delivery, potentially opening new avenues for treating neurodegenerative conditions. This review synthesizes current knowledge and identifies promising directions for future research in biopolymer-based therapeutic strategies.

Three-dimensional (3D) bioprinting holds immense promise for advancing stem cell research and developing novel therapeutic strategies in the field of neural tissue engineering and disease modeling. This paper critically analyzes recent breakthroughs in 3D bioprinting, specifically focusing on its application in these areas. We comprehensively explore the advantages and limitations of various 3D printing methods, the selection and formulation of bioink materials tailored for neural stem cells, and the incorporation of nanomaterials with dual functionality, enhancing the bioprinting process and promoting neurogenesis pathways. Furthermore, the paper reviews the diverse range of stem cells employed in neural bioprinting research, discussing their potential applications and associated challenges. We also introduce the emerging field of 4D bioprinting, highlighting current efforts to develop time-responsive constructs that improve the integration and functionality of bioprinted neural tissues. In short, this manuscript aims to provide a comprehensive understanding of this rapidly evolving field. It underscores the transformative potential of 3D and 4D bioprinting technologies in revolutionizing stem cell research and paving the way for novel therapeutic solutions for neurological disorders and injuries, ultimately contributing significantly to the advancement of regenerative medicine. STATEMENT OF SIGNIFICANCE: This comprehensive review critically examines the current bioprinting research landscape, highlighting efforts to overcome key limitations in printing technologies-improving cell viability post-printing, enhancing resolution, and optimizing cross-linking efficiencies. The continuous refinement of material compositions aims to control the spatiotemporal delivery of therapeutic agents, ensuring better integration of transplanted cells with host tissues. Specifically, the review focuses on groundbreaking advancements in neural tissue engineering. The development of next-generation bioinks, hydrogels, and scaffolds specifically designed for neural regeneration complexities holds the potential to revolutionize treatments for debilitating neural conditions, especially when nanotechnologies are being incorporated. This review offers the readers both a comprehensive analysis of current breakthroughs and an insightful perspective on the future trajectory of neural tissue engineering.

The incidence of nerve tissue injuries, such as peripheral nerve injury, spinal cord injury, traumatic brain injury, and various neurodegenerative diseases (NDs), is continuously increasing because of stress, physical and chemical trauma, and the aging population worldwide. Restoration of the damaged nervous system is challenging because of its structural and functional complexity and limited regenerative ability. Additionally, there is no cure available for NDs except for medications that provide symptomatic relief. Stem cells offer an alternative approach for promoting damage repair, but their efficacy is limited by a compromised survival rate and neurogenesis process. To address these challenges, neural tissue engineering has emerged as a promising strategy in which stem cells are seeded or encapsulated within a suitable biomaterial construct, increasing cell survival and neurogenesis. Numerous biomaterials are utilized to create different types of constructs for this purpose. Researchers are trying to develop ideal scaffolds that combine biomaterials, cells, and molecules that exactly mimic the biological and mechanical properties of the tissue to achieve functional recovery associated with neurological dysfunction. This review focuses on exploring the development and applications of different biomaterials for their potential use in the diagnosis, therapy, nerve tissue regeneration, and treatment of neurological disorders.

Over the past two decades, the development of nerve guide conduits (NGCs) has gained much attention due to the impellent need to find innovative strategies to take care of damaged or degenerated peripheral nerves in clinical surgery. In this view, significant effort has been spent on the development of high-performance NGCs by different materials and manufacturing approaches. Herein, a highly versatile and easy-to-handle route to process 3D porous tubes made of chitosan and gelatin to be used as a nerve guide conduit were investigated. This allowed us to fabricate highly porous substrates with a porosity that ranged from 94.07 ± 1.04% to 97.23 ± 1.15% and average pore sizes-estimated via X-ray computed tomography (XCT) reconstruction and image analysis-of hundreds of microns and an irregular shape with an aspect ratio that ranged from 0.70 ± 0.19 to 0.80 ± 0.15 as a function of the chitosan/gelatin ratio. More interestingly, the addition of gelatin allowed us to modulate the mechanical properties, which gradually reduced the stiffness-max strength from 0.634 ± 0.015 MPa to 0.367 ± 0.021 MPa-and scaffold toughness-from 46.2 kJ/m3 to 14.0 kJ/m3-as the gelatin content increased. All these data fall into the typical ranges of the morphological and mechanical parameters of currently commercialized NGC products. Preliminary in vitro studies proved the ability of 3D porous tubes to support neuroblastoma cell (SH-SY5Y) adhesion and proliferation. In perspective, the proposed approach could also be easily implemented with the integration of other processing techniques (e.g., electrospinning) for the design of innovative bi-layered systems with an improved cell interface and molecular transport abilities.

Biomaterials have been the subject of extensive research, and their applications in medicine and pharmacy are expanding rapidly. Collagen and its derivatives stand out as valuable biomaterials due to their high biocompatibility, biodegradability, and lack of toxicity and immunogenicity. This review comprehensively examines collagen from various sources, its extraction and processing methods, and its structural and functional properties. Preserving the native state of collagen is crucial for maintaining its beneficial characteristics. The challenges associated with chemically modifying collagen to tailor its properties for specific clinical needs are also addressed. The review discusses various collagen-based biomaterials, including solutions, hydrogels, powders, sponges, scaffolds, and thin films. These materials have broad applications in regenerative medicine, tissue engineering, drug delivery, and wound healing. Additionally, the review highlights current research trends related to collagen and its derivatives. These trends may significantly influence future developments, such as using collagen-based bioinks for 3D bioprinting or exploring new collagen nanoparticle preparation methods and drug delivery systems.

Nanomedicine is a newer, promising approach to promote neuroprotection, neuroregeneration, and modulation of the blood-brain barrier. This review includes the integration of various nanomaterials in neurological disorders. In addition, gelatin-based hydrogels, which have huge potential due to biocompatibility, maintenance of porosity, and enhanced neural process outgrowth, are reviewed. Chemical modification of these hydrogels, especially with guanidine moieties, has shown improved neuron viability and underscores tailored biomaterial design in neural applications. This review further discusses strategies to modulate the blood-brain barrier-a factor critically associated with the effective delivery of drugs to the central nervous system. These advances bring supportive solutions to the solving of neurological conditions and innovative therapies for their treatment. Nanomedicine, as applied to neuroscience, presents a significant leap forward in new therapeutic strategies that might help raise the treatment and management of neurological disorders to much better levels. Our aim was to summarize the current state-of-knowledge in this field.

The lack of regeneration of injured neurons in the central and peripheral neural system leads to the failure of damaged tissue repair in patients. While there is no definitive cure for most neurodegenerative diseases, new therapeutic methods that cause the proliferation and differentiation of neurons are of interest. Challenges such as the inability of neuronal cells to proliferate after injury, the lack of a stimulus for initial stimulation, and the presence of the microenvironment around CNS neurons contain several inhibitory factors that prevent neuron regeneration, thus, creating a structure similar to the extracellular matrix helps the cell proliferation in current treatment. A rapid method of neuron-like cell differentiation of PC12 cells is introduced here based on a novel synthetic scaffold. Initially, poly allyldiglycol carbonate (CR-39) substrate is textured under a high dose of ArF UV excimer laser (1000 shot, 300 mJ/pulse equivalent to 300 J/cm2 at 193 nm) to create superficial periodic parallel microchannels with the micrometer spacing and sub-micron width. Ultraviolet treated CR-39 (UT CR-39) provides a suitable scaffold to speed up the transformation/differentiation of PC12 cells. The latter is pheochromocytoma of the rat adrenal medulla as an embryonic origin from the neural crest usually exposed to the nerve growth factor (NGF). In fact, PC12 cells are seeded on the microchannels and simultaneously are stimulated by coherent red photons at 660 nm within the therapeutic window. The UT CR-39 scaffold undergoes extra improvement of ∼ 30% after 12 minutes of laser activation regarding the photo-biomodulation (PBM) mechanism. The cell activation due to the coherent photons also gives rise to enhanced proliferation/differentiation. Here, PC12 cells are efficiently differentiated into neurons according to immunocytochemistry (ICC) and Western Blot verification tests based on MAP2 and synapsin-1 protein expression. In general, UT CR-39 acts as a superior bed to elevate the population of neuron-like cells up to threefold against those of untreated (control)ones. We conclude that the surface cross-linking due to UV exposure and subsequent induced hydrophilicity notably contribute to the neuron-like cell differentiation of PC12 without adding NGF.

Biocompatible polymer-based scaffolds hold great promise for neural repair, especially when they are coupled with electrostimulation to induce neural differentiation. In this study, a combination of polyacrylonitrile/polyaniline (PAN/PANI) and Carbon Nanotubes (CNTs) were used to fabricate three different biomimetic electrospun scaffolds (samples 1, 2 and 3 containing 0.26 wt%, 1 wt% and 2 wt% of CNTs, respectively). These scaffolds underwent thorough characterization for assessing electroconductivity, tensile strength, wettability, degradability, swelling, XRD, and FTIR data. Notably, scanning electron microscopy (SEM) images revealed a three-dimensional scaffold morphology with aligned fibers ranging from 60 nm to 292 nm in diameter. To comprehensively investigate the impact of electrical stimulation on the nervous differentiation of the stem cells seeded on these scaffolds, cell morphology and adhesion were assessed based on SEM images. Additionally, scaffold biocompatibility was studied through MTT assay. Importantly, Real-Time PCR results indicated the expression of neural markers-Nestin,β-tubulin III, and MAP2-by the cells cultured on these samples. In comparison with the control group, samples 1 and 2 exhibited significant increases in Nestin marker expression, indicating early stages of neuronal differentiation, whileβ-tubulin III expression was significantly reduced and MAP2 expression remained statistically unchanged. In contrast, sample 3 did not display a statistically significant upturn in Nestin maker expression, while showcasing remarkable increases in the expression of both MAP2 andβ-tubulin III, as markers of the end stages of differentiation, leading to postmitotic neurons. These results could be attributed to the higher electroconductivity of S3 compared to other samples. Our findings highlight the biomimetic potential of the prepared scaffolds for neural repair, illustrating their effectiveness in guiding stem cell differentiation toward a neural lineage.

Tissue engineering is a multidisciplinary field that merges engineering, material science, and medical biology in order to develop biological alternatives for repairing, replacing, maintaining, or boosting the functionality of tissues and organs. The ultimate goal of tissue engineering is to create biological alternatives for repairing, replacing, maintaining, or enhancing the functionality of tissues and organs. However, the current landscape of tissue engineering techniques presents several challenges, including a lack of suitable biomaterials, inadequate cell proliferation, limited methodologies for replicating desired physiological structures, and the unstable and insufficient production of growth factors, which are essential for facilitating cell communication and the appropriate cellular responses. Despite these challenges, there has been significant progress made in tissue engineering techniques in recent years. Nanoparticles hold a major role within the realm of nanotechnology due to their unique qualities that change with size. These particles, which provide potential solutions to the issues that are met in tissue engineering, have helped propel nanotechnology to its current state of prominence. Despite substantial breakthroughs in the utilization of nanoparticles over the past two decades, the full range of their potential in addressing the difficulties within tissue engineering remains largely untapped. This is due to the fact that these advancements have occurred in relatively isolated pockets. In the realm of tissue engineering, the purpose of this research is to conduct an in-depth investigation of the several ways in which various types of nanoparticles might be put to use. In addition to this, it sheds light on the challenges that need to be conquered in order to unlock the maximum potential of nanotechnology in this area.

Neural tissue engineering has emerged as a promising field that aims to create functional neural tissue for therapeutic applications, drug screening, and disease modelling. It is becoming evident in the literature that this goal requires development of three-dimensional (3D) constructs that can mimic the complex microenvironment of native neural tissue, including its biochemical, mechanical, physical, and electrical properties. These 3D models can be broadly classified as self-assembled models, which include spheroids, organoids, and assembloids, and engineered models, such as those based on decellularized or polymeric scaffolds. Self-assembled models offer advantages such as the ability to recapitulate neural development and disease processes in vitro, and the capacity to study the behaviour and interactions of different cell types in a more realistic environment. However, self-assembled constructs have limitations such as lack of standardised protocols, inability to control the cellular microenvironment, difficulty in controlling structural characteristics, reproducibility, scalability, and lengthy developmental timeframes. Integrating biomimetic materials and advanced manufacturing approaches to present cells with relevant biochemical, mechanical, physical, and electrical cues in a controlled tissue architecture requires alternate engineering approaches. Engineered scaffolds, and specifically 3D hydrogel-based constructs, have desirable properties, lower cost, higher reproducibility, long-term stability, and they can be rapidly tailored to mimic the native microenvironment and structure. This review explores 3D models in neural tissue engineering, with a particular focus on analysing the benefits and limitations of self-assembled organoids compared with hydrogel-based engineered 3D models. Moreover, this paper will focus on hydrogel based engineered models and probe their biomaterial components, tuneable properties, and fabrication techniques that allow them to mimic native neural tissue structures and environment. Finally, the current challenges and future research prospects of 3D neural models for both self-assembled and engineered models in neural tissue engineering will be discussed.

Spinal cord injury (SCI) is an important factor in sensory and motor disorders that affects thousands of people every year. Currently, despite successes in basic science and clinical research, there are few effective methods in the treatment of chronic and acute spinal cord injuries. In the last decade, the use of 3D printed scaffolds in the treatment of SCI had satisfactory and promising results. By providing a microenvironment around the injury site and in combination with growth factors or cells, 3D printed scaffolds help in axon regeneration as well as neural recovery after SCI. Here, we provide an overview of tissue engineering, 3D printing scaffolds, the different polymers used and their characterization methods. This review highlights the recent encouraging applications of 3D printing scaffolds in developing the novel SCI therapy.

Severe spinal cord injuries (SCI) lead to loss of functional activity of the body below the injury site, affect a person's ability to self-care and have a direct impact on performance. Due to the structural features and functional role of the spinal cord in the body, the consequences of SCI cannot be completely overcome at the expense of endogenous regenerative potential and, developing over time, lead to severe complications years after injury. Thus, the primary task of this type of injury treatment is to create artificial conditions for the regenerative growth of damaged nerve fibers through the area of the SCI. Solving this problem is possible using tissue neuroengineering involving the technology of replacing the natural tissue environment with synthetic matrices (for example, hydrogels) in combination with stem cells, in particular, neural/progenitor stem cells (NSPCs). This approach can provide maximum stimulation and support for the regenerative growth of axons of damaged neurons and their myelination. In this review, we consider the currently available options for improving the condition after SCI (use of NSC transplantation or/and replacement of the damaged area of the SCI with a matrix, specifically a hydrogel). We emphasise the expediency and effectiveness of the hydrogel matrix + NSCs complex system used for the reconstruction of spinal cord tissue after injury. Since such a complex approach (a combination of tissue engineering and cell therapy), in our opinion, allows not only to creation of conditions for supporting endogenous regeneration or mechanical reconstruction of the spinal cord, but also to strengthen endogenous regeneration, prevent the spread of the inflammatory process, and promote the restoration of lost reflex, motor and sensory functions of the injured area of spinal cord.

Traumatic injuries, neurodegenerative diseases and oxidative stress serve as the early biomarkers for neuronal damage and impede angiogenesis and subsequently neuronal growth. Considering this, the present work aimed to develop a poly(N-acryloylglycine)-co-(acrylamide)-co-(N-acryloylglutamate) hydrogel [p(NAG-Ac-NAE)] with angiogenesis/neurogenesis properties. As constituents of this polymer modulate their vital role in biological functions, inhibitory neurotransmitter glycine regulates neuronal homeostasis, and glutamatergic signalling regulates angiogenesis. The p(NAG-Ac-NAE) hydrogel is a highly branched, biodegradable and pH-responsive polymer with a very high swelling behavior of 6188%. The mechanical stability (G', 2.3-2.7 kPa) of this polymeric hydrogel is commendable in the differentiation of mature neurons. This hydrogel is biocompatible (as tested in HUVEC cells) and helps to proliferate PC12 cells (152.7 ± 13.7%), whereas it is cytotoxic towards aggressive cancers such as glioblastoma (LN229 cells) and triple negative breast cancer (TNBC; MDA-MB-231 cells) and helps to maintain the healthy cytoskeleton framework structure of primary cortical neurons by facilitating the elongation of the axonal pathway. Furthermore, FACS results revealed that the synthesized hydrogel potentiates neurogenesis by inducing the cell cycle (G0/G1) and arresting the sub-G1 phase by limiting apoptosis. Additionally, RT-PCR results revealed that this hydrogel induced an increased level of HIF-1α expression, providing preconditioning effects towards neuronal cells under oxidative stress by scavenging ROS and initiating neurogenic and angiogenic signalling. This hydrogel further exhibits more pro-angiogenic activities by increasing the expression of VEGF isoforms compared to previously reported hydrogels. In conclusion, the newly synthesized p(NAG-Ac-NAE) hydrogel can be one of the potential neuroregenerative materials for vasculogenesis-assisted neurogenic applications and paramount for the management of neurodegenerative diseases.

Molybdenum disulfide (MoS2) has excellent physical and chemical properties. Further, chiral MoS2 (CMS) exhibits excellent chiroptical and enantioselective effects, and the enantioselective properties of CMS have been studied for the treatment of neurodegenerative diseases. Intriguingly, left- and right-handed materials have different effects on promoting the differentiation of neural stem cells into neurons. However, the effect of the enantioselectivity of chiral materials on peripheral nerve regeneration remains unclear.

In this study, CMS@bacterial cellulose (BC) scaffolds were fabricated using a hydrothermal approach. The CMS@BC films synthesized with L-2-amino-3-phenyl-1-propanol was defined as L-CMS. The CMS@BC films synthesized with D-2-amino-3-phenyl-1-propanol was defined as D-CMS. The biocompatibility of CMS@BC scaffolds and their effect on Schwann cells (SCs) were validated by cellular experiments. In addition, these scaffolds were implanted in rat sciatic nerve defect sites for three months.

These chiral scaffolds displayed high hydrophilicity, good mechanical properties, and low cytotoxicity. Further, we found that the L-CMS scaffolds were superior to the D-CMS scaffolds in promoting SCs proliferation. After three months, the scaffolds showed good biocompatibility in vivo, and the nerve conducting velocities of the L-CMS and D-CMS scaffolds were 51.2 m/s and 26.8 m/s, respectively. The L-CMS scaffolds showed a better regenerative effect than the D-CMS scaffolds. Similarly, the sciatic nerve function index and effects on the motor and electrophysiological functions were higher for the L-CMS scaffolds than the D-CMS scaffolds. Finally, the axon diameter and myelin sheath thickness of the regenerated nerves were improved in the L-CMS group.

We found that the CMS@BC can promote peripheral nerve regeneration, and in general, the L-CMS group exhibited superior repair performance. Overall, the findings of this study reveal that CMS@BC can be used as a chiral nanomaterial nerve scaffold for peripheral nerve repair.

Neural tissue engineering is a sub-field of tissue engineering that develops neural tissue. Damaged central and peripheral nervous tissue can be fabricated with a suitable scaffold printed with biomaterials. These scaffolds promote cell growth, development, and migration, yet they vary according to the biomaterial and scaffold printing technique, which determine the physical and biochemical properties. The physical and biochemical properties of scaffolds stimulate diverse signalling pathways, such as Wnt, NOTCH, Hedgehog, and ion channels- mediated pathways to promote neuron migration, elongation and migration. However, neurotransmitters like dopamine, acetylcholine, gamma amino butyric acid, and other signalling molecules are critical in neural tissue engineering to tissue fabrication. Thus, this review focuses on neural tissue regeneration with a tissue engineering approach highlighting the signalling pathways. Further, it explores the interaction of the scaffolds with the signalling pathways for generating neural tissue.

Spinal cord injury, traumatic brain injury, and neurosurgery procedures usually lead to neural tissue damage. Self-assembled peptide (SAP) hydrogels, a type of innovative hierarchical nanofiber-forming peptide sequences serving as hydrogelators, have emerged as a promising solution for repairing tissue defects and promoting neural tissue regeneration. SAPs possess numerous features, such as adaptable morphologies, biocompatibility, injectability, tunable mechanical stability, and mimicking of the native extracellular matrix. This review explores the capacity of neural cell regeneration and examines the critical aspects of SAPs in neuroregeneration, including their biochemical composition, topology, mechanical behavior, conductivity, and degradability. Additionally, it delves into the latest strategies involving SAPs for central or peripheral neural tissue engineering. Finally, the prospects of SAP hydrogel design and development in the realm of neuroregeneration are discussed.

In tissue engineering, 3D printing represents a versatile technology employing inks to construct three-dimensional living structures, mimicking natural biological systems. This technology efficiently translates digital blueprints into highly reproducible 3D objects. Recent advances have expanded 3D printing applications, allowing for the fabrication of diverse anatomical components, including engineered functional tissues and organs. The development of printable inks, which incorporate macromolecules, enzymes, cells, and growth factors, is advancing with the aim of restoring damaged tissues and organs. Polysaccharides, recognized for their intrinsic resemblance to components of the extracellular matrix have garnered significant attention in the field of tissue engineering. This review explores diverse 3D printing techniques, outlining distinctive features that should characterize scaffolds used as ideal matrices in tissue engineering. A detailed investigation into the properties and roles of polysaccharides in tissue engineering is highlighted. The review also culminates in a profound exploration of 3D polysaccharide-based hydrogel applications, focusing on recent breakthroughs in regenerating different tissues such as skin, bone, cartilage, heart, nerve, vasculature, and skeletal muscle. It further addresses challenges and prospective directions in 3D printing hydrogels based on polysaccharides, paving the way for innovative research to fabricate functional tissues, enhancing patient care, and improving quality of life.

In recent years, researchers have increasingly directed their focus toward the biomedical field, driven by the goal of engineering polymer systems that possess a unique combination of both electrical conductivity and biodegradability. This convergence of properties holds significant promise, as it addresses a fundamental requirement for biomedical applications: compatibility with biological environments. These polymer systems are viewed as auspicious biomaterials, precisely because they meet this critical criterion. Beyond their biodegradability, these materials offer a range of advantageous characteristics. Their exceptional processability enables facile fabrication into various forms, and their chemical stability ensures reliability in diverse physiological conditions. Moreover, their low production costs make them economically viable options for large-scale applications. Notably, their intrinsic electrical conductivity further distinguishes them, opening up possibilities for applications that demand such functionality. As the focus of this review, a survey into the use of biodegradable conducting polymers in tissue engineering, biomedical implants, and antibacterial applications is conducted.

Current management of anesthesia-associated complications falls short in terms of both efficacy and safety. Nanomaterials with versatile properties and unique nano-bio interactions hold substantial promise as therapeutics for addressing these complications. This review conducts a thorough examination of the existing nanotherapeutics and highlights the strategies for developing prospective nanomedicines to mitigate anesthetics-related toxicity. Initially, general, regional, and local anesthesia along with the commonly used anesthetics and related prevalent side effects are introduced. Furthermore, employing nanotechnology to prevent and alleviate the complications of anesthetics is systematically demonstrated from three aspects, that is, developing 1) safe nano-formulization for anesthetics; 2) nano-antidotes to sequester overdosed anesthetics and alter their pharmacokinetics; 3) nanomedicines with pharmacodynamic activities to treat anesthetics toxicity. Finally, the prospects and challenges facing the clinical translation of nanotherapeutics for anesthesia-related complications are discussed. This work provides a comprehensive roadmap for developing effective nanotherapeutics to prevent and mitigate anesthesia-associated toxicity, which can potentially revolutionize the management of anesthesia complications.

Brain damage is a common tissue damage caused by trauma or diseases, which can be life-threatening. Stem cell implantation is an emerging strategy treating brain damage. The stem cell is commonly embedded in a matrix material for implantation, which protects stem cell and induces cell differentiation. Cell differentiation induction by this material is decisive in the effectiveness of this treatment strategy. In this work, we present an injectable fibroin/MXene conductive hydrogel as stem cell carrier, which further enables in-vivo electrical stimulation upon stem cells implanted into damaged brain tissue. Cell differentiation characterization of stem cell showed high effectiveness of electrical stimulation in this system, which is comparable to pure conductive membrane. Axon growth density of the newly differentiated neurons increased by 290% and axon length by 320%. In addition, unfavored astrocyte differentiation is minimized. The therapeutic effect of this system is proved through traumatic brain injury model on rats. Combined with in vivo electrical stimulation, cavities formation is reduced after traumatic brain injury, and rat motor function recovery is significantly promoted.

The replacement and regeneration of biological tissues by fabricating three-dimensional functionalized constructs that can improve material interaction with cells is an important challenge of tissue engineering. In this study, bioactive and biomimetic scaffolds based on chitosan-alginate polyelectrolyte complexes (PECs) were fabricated by freeze-drying method and then crosslinked with CaCl2. Various chitosan-alginate (CS-AL) molar ratios were used to obtain PECs with different structural and mechanical properties. The CS1-AL2.3 scaffold showed to possess the best mechanical properties (8 MPa) and good pore morphology with an average size of 100-150 μm. After the crosslinking process, a less porous structure but with higher elastic modulus (30 MPa) was obtained. To make matrix bioactive and biomimetic, the CS1-AL2.3 system was first functionalized with 3,4-dihydroxyhydrocinnamic acid (HCAF) and then with PySO3 or Heparin to introduce groups/molecules mimicking the extracellular matrix. While the antioxidant properties of the scaffolds containing HCAF improved by 3 orders of magnitude, compared to the non-functionalized matrix, the introduction of sulfonic groups into the bioactive scaffold made the structure more porous and hydrophilic with respect to the heparinized one also favoring the penetration and proliferation of fibroblasts into the scaffold. These results indicate the potential of these novel systems for tissue engineering.

Alzheimer's disease is a neurological disorder that causes increased memory loss, mood swings, behavioral disorders, and disruptions in daily activities. Polymer scaffolds for the brain have been grown under laboratory, physiological, and pathological circumstances because of the limitations of conventional treatments for patients with central nervous system diseases. The blood-brain barrier prevents medications from entering the brain, challenging AD treatment. Numerous biomaterials such as biomolecules, polymers, inorganic metals, and metal oxide nanoparticles have been used to transport therapeutic medicines into the nervous system. Incorporating biocompatible materials that support neurogenesis through a combination of topographical, pharmacological, and mechanical stimuli has also shown promise for the transfer of cells to replenish dopaminergic neurons. Components made of naturally occurring biodegradable polymers are appropriate for the regeneration of nerve tissue. The ability of natural-based materials (biomaterials) has been shown to promote endogenous cell development after implantation. Also, strategic functionalization of polymeric nanocarriers could be employed for treating AD. In particular, nanoparticles could resolve Aβ aggregation and thus help cure Alzheimer's disease. Drug moieties can be effectively directed to the brain by utilizing nano-based systems and diverse colloidal carriers, including hydrogels and biodegradable scaffolds. Notably, early investigations employing neural stem cells have yielded promising results, further emphasizing the potential advancements in this field. Few studies have fully leveraged the combination of cells with cutting-edge biomaterials. This study provides a comprehensive overview of prior research, highlighting the pivotal role of biomaterials as sophisticated drug carriers. It delves into various intelligent drug delivery systems, encompassing pH and thermo-triggered mechanisms, polymeric and lipid carriers, inorganic nanoparticles, and other vectors. The discussion synthesizes existing knowledge and underscores the transformative impact of these biomaterials in devising innovative strategies, augmenting current therapeutic methodologies, and shaping new paradigms in the realm of Alzheimer's disease treatment.

Neurodegenerative diseases arise due to slow and gradual loss of structure and/or function of neurons and glial cells and cause different degrees of loss of cognition abilities and sensation. The little success in developing effective treatments imposes a high and regressive economic impact on society, patients and their families. In recent years, regenerative medicine has provided a great opportunity to research new innovative strategies with strong potential to treatleva these diseases. These effects are due to the ability of suitable cells and biomaterials to regenerate damaged nerves with differentiated cells, creating an appropriate environment for recovering or preserving existing healthy neurons and glial cells from destruction and damage. Ultimately, a better understanding and thus a further investigation of stem cell technology, tissue engineering, gene therapy, and exosomes allows progress towards practical and effective treatments for neurodegenerative diseases. Therefore, in this review, advances currently being developed in regenerative medicine using animal models and human clinical trials in neurological disorders are summarized.

Agro-food waste is a rich source of biopolymers such as cellulose, chitin, and starch, which have been shown to possess excellent biocompatibility, biodegradability, and low toxicity. These properties make biopolymers from agro-food waste for its application in tissue engineering and regenerative medicine. Thus, this review highlighted the properties, processing methods, and applications of biopolymers derived from various agro-food waste sources. We also highlight recent advances in the development of biopolymers from agro-food waste and their potential for future tissue engineering and regenerative medicine applications, including drug delivery, wound healing, tissue engineering, biodegradable packaging, excipients, dental applications, diagnostic tools, and medical implants. Additionally, it explores the challenges, prospects, and future directions in this rapidly evolving field. The review showed the evolution of production techniques for transforming agro-food waste into valuable biopolymers. However, these biopolymers serving as the cornerstone in scaffold development and drug delivery systems. With their role in wound dressings, cell encapsulation, and regenerative therapies, biopolymers promote efficient wound healing, cell transplantation, and diverse regenerative treatments. Biopolymers support various regenerative treatments, including cartilage and bone regeneration, nerve repair, and organ transplantation. Overall, this review concluded the potential of biopolymers from agro-food waste as a sustainable and cost-effective solution in tissue engineering and regenerative medicine, offering innovative solutions for medical treatments and promoting the advancement of these fields.

The central nervous system's limited capacity for regeneration often leads to permanent neuronal loss following injury. Reprogramming resident reactive astrocytes into induced neurons at the site of injury is a promising strategy for neural repair, but challenges persist in stabilizing and accurately targeting viral vectors for transgene expression. In this study, we employed a bioinspired self-assembling peptide (SAP) hydrogel for the precise and controlled release of a hybrid adeno-associated virus (AAV) vector, AAVDJ, carrying the NeuroD1 neural reprogramming transgene. This method effectively mitigates the issues of high viral dosage at the target site, off-target delivery, and immunogenic reactions, enhancing the vector's targeting and reprogramming efficiency. In vitro, this vector successfully induced neuron formation, as confirmed by morphological, histochemical, and electrophysiological analyses. In vivo, SAP-mediated delivery of AAVDJ-NeuroD1 facilitated the trans-differentiation of reactive host astrocytes into induced neurons, concurrently reducing glial scarring. Our findings introduce a safe and effective method for treating central nervous system injuries, marking a significant advancement in regenerative neuroscience.

The prevalence of facial nerve injury is substantial, and the restoration of its structure and function remains a significant challenge. Autologous nerve transplantation is a common treatment for severed facial nerve injury; however, it has great limitations. Therefore, there is an urgent need for clinical repair methods that can rival it. Tissue engineering nerve conduits are usually composed of scaffolds, cells and neurofactors. Tissue engineering is regarded as a promising method for facial nerve regeneration. Among different factors, the porous nerve conduit made of organic materials, which has high porosity and biocompatibility, plays an indispensable role. This review introduces facial nerve injury and the existing treatment methods and discusses the necessity of the application of porous nerve conduit. We focus on the application of porous organic polymer materials from production technology and material classification and summarize the necessity and research progress of these in repairing severed facial nerve injury, which is relatively rare in the existing articles. This review provides a theoretical basis for further research into and clinical interventions on facial nerve injury and has certain guiding significance for the development of new materials.

The loss or failure of an organ/tissue stands as one of the healthcare system's most prevalent, devastating, and costly challenges. Strategies for neural tissue repair and regeneration have received significant attention due to their particularly strong impact on patients' well-being. Many research efforts are dedicated not only to control the disease symptoms but also to find solutions to repair the damaged tissues. Neural tissue engineering (TE) plays a key role in addressing this problem and significant efforts are being carried out to develop strategies for neural repair treatment. In the last years, active materials allowing to tune cell-materials interaction are being increasingly used, representing a recent paradigm in TE applications. Among the most important stimuli influencing cell behavior are the electrical and mechanical ones. In this way, materials with the ability to provide this kind of stimuli to the neural cells seem to be appropriate to support neural TE. In this scope, this review summarizes the different biomaterials types used for neural TE, highlighting the relevance of using active biomaterials and electrical stimulation. Furthermore, this review provides not only a compilation of the most relevant studies and results but also strategies for novel and more biomimetic approaches for neural TE.

Hydrogels have immense potential in revolutionizing central nervous system (CNS) drug delivery, improving outcomes for neurological disorders. They serve as promising tools for controlled drug delivery to the CNS. Available hydrogel types include natural macromolecules (e.g., chitosan, hyaluronic acid, alginate), as well as hybrid hydrogels combining natural and synthetic polymers. Each type offers distinct advantages in terms of biocompatibility, mechanical properties, and drug release kinetics. Design and engineering considerations encompass hydrogel composition, crosslinking density, porosity, and strategies for targeted drug delivery. The review emphasizes factors affecting drug release profiles, such as hydrogel properties and formulation parameters. CNS drug delivery applications of hydrogels span a wide range of therapeutics, including small molecules, proteins and peptides, and nucleic acids. However, challenges like limited biodegradability, clearance, and effective CNS delivery persist. Incorporating 3D bioprinting technology with hydrogel-based CNS drug delivery holds the promise of highly personalized and precisely controlled therapeutic interventions for neurological disorders. The review explores emerging technologies like 3D bioprinting and nanotechnology as opportunities for enhanced precision and effectiveness in hydrogel-based CNS drug delivery. Continued research, collaboration, and technological advancements are vital for translating hydrogel-based therapies into clinical practice, benefiting patients with CNS disorders. This comprehensive review article delves into hydrogels for CNS drug delivery, addressing their types, design principles, applications, challenges, and opportunities for clinical translation.

Neuronal disorders are characterized by the loss of functional neurons and disrupted neuroanatomical connectivity, severely impacting the quality of life of patients. This study investigates a novel electroconductive nanocomposite consisting of glycine-derived carbon nanodots (GlyCNDs) incorporated into a collagen matrix and validates its beneficial physicochemical and electro-active cueing to relevant cells. To this end, this work employs mouse induced pluripotent stem cell (iPSC)-derived neural progenitor (NP) spheroids. The findings reveal that the nanocomposite markedly augmented neuronal differentiation in NP spheroids and stimulate neuritogenesis. In addition, this work demonstrates that the biomaterial-driven enhancements of the cellular response ultimately contribute to the development of highly integrated and functional neural networks. Lastly, acute dizocilpine (MK-801) treatment provides new evidence for a direct interaction between collagen-bound GlyCNDs and postsynaptic N-methyl-D-aspartate (NMDA) receptors, thereby suggesting a potential mechanism underlying the observed cellular events. In summary, the findings establish a foundation for the development of a new nanocomposite resulting from the integration of carbon nanomaterials within a clinically approved hydrogel, toward an effective biomaterial-based strategy for addressing neuronal disorders by restoring damaged/lost neurons and supporting the reestablishment of neuroanatomical connectivity.

The need for biocompatible drug carriers has been significantly increased from the past few years. Researchers show great interest in the development of more versatile and sophisticated biomaterials based drug carriers. Hydrogels are beneficial drug carriers and easily release the controlled amount of drug at target site due to its tunable structure. The hydrogels made-up of potent biological macromolecules including collagen, gelatin, fibrin, elastin, fibroin, chitosan, starch, alginate, agarose and carrageenan have been proven as versatile biomaterials. These are three-dimensional polymeric networks, synthesized by crosslinking of hydrophilic polymers. The biological macromolecules based hydrogels containing therapeutic substances are used in a wide range of biomedical applications including wound healing, tissue engineering, cosmetics and contact lenses. However, many aspects related to hydrogels such as the mechanism of cross-linking and molecular entanglement are not clear. So, there is a need to do more research and exploration toward the extensive and cost-effective use of hydrogels. The present review article elaborately discusses the biomolecules based hydrogels and their possible biomedical applications in different fields.

Biomaterials able to promote neuronal development and neurite outgrowth are highly desired in neural tissue engineering for the repair of damaged or disrupted neural tissue and restoring the axonal connection. For this purpose, the use of either electroactive or micro- and nanostructured materials has been separately investigated. Here, the use of a nanomodulated conductive poly(3,4-ethylendioxithiophene) poly(styrenesulfonate) (PEDOT/PSS) substrate that exhibits instructive topographical and electrical cues at the same time was investigated for the first time. In particular, thin films featuring grooves with sizes comparable with those of neuronal neurites (NanoPEDOT) were fabricated by electrochemical polymerization of PEDOT/PSS on a nanomodulated polycarbonate template. The ability of NanoPEDOT to support neuronal development and direct neurite outgrowth was demonstrated by assessing cell viability and proliferation, expression of neuronal markers, average neurite length, and direction of neuroblastoma N2A cells induced to differentiate on this novel support. In addition to the beneficial effect of the nanogrooved topography, a 30% increase was shown in the average length of neurites when differentiating cells were subjected to an electrical stimulation of a few microamperes for 6 h. The results reported here suggest a favorable effect on the neuronal development of the synergistic combination of nanotopography and electrical stimulation, supporting the use of NanoPEDOT in neural tissue engineering to promote physical and functional reconnection of impaired neural networks.

Emerging nanotechnologies offer numerous opportunities in the field of regenerative medicine and have been widely explored to design novel scaffolds for the regeneration and stimulation of nerve tissue. In this review, we focus on peripheral nerve regeneration. First, we introduce the biomedical problem and the present status of nerve conduits that can be used to guide, fasten and enhance regeneration. Then, we thoroughly discuss graphene as an emerging candidate in nerve tissue engineering, in light of its chemical, tribological and electrical properties. We introduce the graphene forms commonly used as neural interfaces, briefly review their applications, and discuss their potential toxicity. We then focus on the adoption of graphene in peripheral nervous system applications, a research field that has gained in the last years ever-increasing attention. We discuss the potential integration of graphene in guidance conduits, and critically review graphene interaction not only with peripheral neurons, but also with non-neural cells involved in nerve regeneration; indeed, the latter have recently emerged as central players in modulating the immune and inflammatory response and accelerating the growth of new tissue.

Implantable neural interfaces (NIs) have emerged in the clinic as outstanding tools for the management of a variety of neurological conditions caused by trauma or disease. However, the foreign body reaction triggered upon implantation remains one of the major challenges hindering the safety and longevity of NIs. The integration of tools and principles from biomaterial design and tissue engineering has been investigated as a promising strategy to develop NIs with enhanced functionality and performance. In this Feature Article, we highlight the main bioengineering approaches for the development of biohybrid NIs with an emphasis on relevant device design criteria. Technical and scientific challenges associated with the fabrication and functional assessment of technologies composed of both artificial and biological components are discussed. Lastly, we provide future perspectives related to engineering, regulatory, and neuroethical challenges to be addressed towards the realisation of the promise of biohybrid neurotechnology.

At present, peripheral nerve injuries (PNIs) are one of the leading causes of substantial impairment around the globe. Complete recovery of nerve function after an injury is challenging. Currently, autologous nerve grafts are being used as a treatment; however, this has several downsides, for example, donor site morbidity, shortage of donor sites, loss of sensation, inflammation, and neuroma development. The most promising alternative is the development of a nerve guide conduit (NGC) to direct the restoration and renewal of neuronal axons from the proximal to the distal end to facilitate nerve regeneration and maximize sensory and functional recovery. Alternatively, the response of nerve cells to electrical stimulation (ES) has a substantial regenerative effect. The incorporation of electrically conductive biomaterials in the fabrication of smart NGCs facilitates the function of ES throughout the active proliferation state. This article overviews the potency of the various categories of electroactive smart biomaterials, including conductive and piezoelectric nanomaterials, piezoelectric polymers, and organic conductive polymers that researchers have employed latterly to fabricate smart NGCs and their potentiality in future clinical application. It also summarizes a comprehensive analysis of the recent research and advancements in the application of ES in the field of NGC.

Electrical stimulation (ES) within a conductive scaffold is potentially beneficial in encouraging the differentiation of stem cells toward a neuronal phenotype. To improve stem cell-based regenerative therapies, it is essential to use electroconductive scaffolds with appropriate stiffnesses to regulate the amount and location of ES delivery. Herein, biodegradable electroconductive substrates with different stiffnesses are fabricated from chitosan-grafted-polyaniline (CS-g-PANI) copolymers. Human mesenchymal stem cells (hMSCs) cultured on soft conductive scaffolds show a morphological change with significant filopodial elongation after electrically stimulated culture along with upregulation of neuronal markers and downregulation of glial markers. Compared to stiff conductive scaffolds and non-conductive CS scaffolds, soft conductive CS-g-PANI scaffolds promote increased expression of microtubule-associated protein 2 (MAP2) and neurofilament heavy chain (NF-H) after application of ES. At the same time, there is a decrease in the expression of the glial markers glial fibrillary acidic protein (GFAP) and vimentin after ES. Furthermore, the elevation of intracellular calcium [Ca2+ ] during spontaneous, cell-generated Ca2+ transients further suggests that electric field stimulation of hMSCs cultured on conductive substrates can promote a neural-like phenotype. The findings suggest that the combination of the soft conductive CS-g-PANI substrate and ES is a promising new tool for enhancing neuronal tissue engineering outcomes.