Self-assembling peptide nanofiber hydrogels for central nervous system regeneration

Central nervous system (CNS) presents a complex regeneration problem due to the inability of central neurons to regenerate correct axonal and dendritic connections. However, recent advances in developmental neurobiology, cell signaling, cell--matrix interaction, and biomaterials technologies have forced a reconsideration of CNS regeneration potentials from the viewpoint of tissue engineering and regenerative medicine. The applications of a novel tissue regeneration-inducing biomaterial and stem cells are thought to be critical for the mission. The use of peptide nanofiber hydrogels in cell therapy and tissue engineering offers promising perspectives for CNS regeneration. Self-assembling peptide undergo a rapid transformation from liquid to gel upon addition of counterions or pH adjustment, directly integrating with the host tissue. The peptide nanofiber hydrogels have mechanical properties that closely match the native central nervous extracellular matrix, which could enhance axonal growth. Such materials can provide an optimal three dimensional microenvironment for encapsulated cells. These materials can also be tailored with bioactive motifs to modulate the wound environment and enhance regeneration. This review intends to detail the recent status of self-assembling peptide nanofiber hydrogels for CNS regeneration.     

Functionalized Metal–Organic Framework-Modified Hydrogel That Breaks the Vicious Cycle of Inflammation and ROS for Repairing of Diabetic Bone Defects

The regeneration of diabetic bone defects remains challenging. Hyperglycemia causes inflammation state and excessive reactive oxygen species (ROS) during bone regeneration period. These two effects reinforce one another and create an endless loop that is also accompanied by mitochondrial dysfunction. However, there is still no effective and inclusive method targeting at the two aspects and breaking the vicious cycle. Herein, nanoparticles-Met@ZIF-8(metformin loaded zeolitic imidazolate frameworks) modified hydrogel that is capable of releasing metformin and Zn elements are constructed. This hydrogel treats hyperglycemia while also controlling mitochondrial function, reducing inflammation, and restoring homeostasis. In addition, the synergetic effect from metformin and Zn ions inhibits ROS-inflammation cascade generation and destroys the continuous progress by taking effects in both ROS and inflammation and further keeping organelles’ homeostasis. Furthermore, with the recovery of mitochondria and breakdown of the ROS-inflammation cascade cycle, osteogenesis under a diabetic microenvironment is enhanced in vivo and in vitro. In conclusion, the study provides critical insight into the biological mechanism and potential therapy for diabetic bone regeneration.     

Large-Scale Fabrication of Robust Artificial Skins from a Biodegradable Sealant-Loaded Nanofiber Scaffold to Skin Tissue via Microfluidic Blow-Spinning

Given that many people suffer from large-area skin damage, skin regeneration is a matter of high concern. Here, an available method is developed for the formation of large-area robust skins through three stages: fabrication of a biodegradable sealant-loaded nanofiber scaffold (SNS), skin tissue reconstruction, and skin regeneration. First, a microfluidic blow-spinning strategy is proposed to fabricate a large-scale nanofiber scaffold with an area of 140 cm × 40 cm, composed of fibrinogen-loaded polycaprolactone/silk fibroin (PCL/SF) ultrafine core–shell nanofibers with mean diameter of 65 nm. Then, the SNS forms, where the gelling reaction of fibrin sealant occurs in situ between thrombin and fibrinogen on PCL/SF nanofiber surface, to promote the migration and proliferation of fibroblasts, accelerating skin regeneration. Through an in vivo study, it is shown that the SNS can rapidly repair acute tissue damage such as vascular bleeding and hepatic hemorrhage, and also promote angiogenesis, large-area abdominal wall defect repair, and wound tissue regeneration for medical problems in the world. Besides, it avoids the risk of immune rejection and secondary surgery in clinical applications. This strategy offers a facile route to regenerate large-scale robust skin, which shows great potential in abdominal wall defect repair.     

Recapitulating Antioxidant and Antibacterial Compounds into a Package for Tissue Regeneration: Dual Function Materials with Synergistic Effect

Oxidative damage and infection can prevent or delay tissue repair. Moreover, infection reinforces reactive oxygen species (ROS) formation, which makes the wound's condition even worse. Therefore, the need for antioxidant and antibacterial agents is felt for tissue regeneration. There are emerging up-and-coming biomaterials that recapitulate both properties into a package, offering an effective solution to turn the wound back into a healing state. In this article, the principles of antioxidant and antibacterial activity are summarized. The review starts with biological aspects, getting the readers to familiarize themselves with tissue barriers against infection. This is followed by the chemistry and mechanism of action of antioxidant and antibacterial materials (dual function). Eventually, the outlook and challenges are underlined to provide where the dual-function biomaterials are and where they are going in the future. It is expected that the present article inspires the designing of dual-function biomaterials to more advanced levels by providing the fundamentals and comparative points of view and paving the clinical way for these materials.     

Nanofibrous membrane of collagen–polycaprolactone for cell growth and tissue regeneration

Nanofibrous substrates of synthetic polymers including polycaprolactone (PCL) have shown considerable potential in tissue regeneration. This paper reports the use of PCL/collagen nanofibers to improve the in vitro osteoblastic responses for the applications in bone regeneration area. Collagen and PCL were dissolved in a co-solvent, and the resulting solution was electrospun into a nanofibrous web. Nonwoven fibrous matrices were successfully produced at various compositional ratios (PCL/collagen = 1/3, 1 and 3 by weight). Although the PCL nanofiber was hydrophobic, the presence of collagen significantly improved the water affinity, such as the water contact angle and water uptake capacity. Tensile mechanical tests showed that the collagen–PCL nanofiber had a significantly higher extension rate (approximately 2.8-fold) than the PCL while maintaining the maximum tensile load in a similar range. The osteoblastic cells cultured on the collagen–PCL nanofibrous substrate showed better initial adhesion and a higher level of growth than those cultured on the PCL nanofiber. Furthermore, real-time RT-PCR revealed the expression of a series of bone-associated genes, including osteopontin, collagen type I and alkaline phosphatase. The expression of these genes was significantly higher on the collagen–PCL nanofiber than on the PCL nanofiber. When subcutaneously implanted in mouse the collagen–PCL membrane facilitated tissue cells to well penetrate into the nanofibrous structure at day 7, whilst no such cell penetration was noticed in the pure PCL nanofiber. Overall, the presence of collagen within the PCL nanofiber improves the water affinity, tensile extension rate, and the tissue cell responses, such as initial adhesion, growth, penetration and the expression of bone-associated genes. Therefore, the collagen–PCL nanofibrous membrane may have potential applications in the cell growth and bone tissue regeneration.     

Multifunction ZnO/carbon hybrid nanofiber mats for organic dyes treatment via photocatalysis with enhanced solar-driven evaporation

ZnO-based photocatalytic materials have received widespread attention due to their usefulness than other photocatalytic materials in organic dye wastewater treatment. However, its photocatalytic efficiency and surface stability limit further applicability. This paper uses a one-step carbonization method to prepare multifunctional ZnO/carbon hybrid nanofiber mats. The carbonization creates a π-conjugated carbonaceous structure of the mats, which prolongs the electron recovery time of ZnO nanoparticles to yield improved photocatalytic efficiency. Further, the carbonization reduces the fiber diameter of the carbon hybrid nanofiber mats, which quadruples the specific surface area to yield enhanced adsorption and photocatalytic performance. At the same time, the prepared nanofiber mats can increase the evaporation rate of water under solar irradiation to a level of 1.46 kg·m⁻²·h⁻¹ with an efficiency of 91.9%. Thus, the nanofiber mats allow the facile incorporation of photocatalysts to clean contaminated water through adsorption, photodegradation, and interfacial heat-assisted distillation mechanisms.     

Composite nanofiber of bioactive glass nanofiller incorporated poly(lactic acid) for bone regeneration

A novel composite nanofiber of poly(lactic acid) (PLA) incorporated with the nanocomponent of bioactive glass was exploited using an electrospinning method. Small concentrations of the bioactive glass phase added up to 10% facilitated the generation of a nanofibrous matrix with hundreds of nanometers in diameter without a formation of beads. The addition of the bioactive glass phase greatly enhanced the in vitro apatite formation on the nanofiber surface under a body simulating medium. Osteoblastic cells were demonstrated to adhere well on the composite nanofiber and grow actively with culturing time, suggesting its usefulness as a supporting matrix for the hard tissue regeneration.     

The interplay between hemostasis and immune response in biomaterial development for osteogenesis

Treatment of large bone defects, particularly bone non-union, remains a clinical challenge. The gold-standard bone substitute continues to be an autologous bone graft, which is difficult to be replaced with synthetic biomaterials. Considering these aspects, strategies should be formulated to develop advanced materials for functional bone regeneration. Recent studies have revealed that hematoma (the first tissue structure formed at the bone injury site) plays an essential role in bone healing. Hematoma consists of a fibrin clot, infiltrated immune cells, and tissue progenitor cells. It bridges the bone defect and provides a microenvironment for the interplay between hemostasis and the immune systems. Moreover, an ideal fibrin structure with appropriate fiber thickness and density could facilitate bone regeneration, and biomaterial implantation could affect fibrin structure. Meanwhile, immunoregulation plays an essential role in bone healing. In particular, materials inducing a shift from inflammatory to anti-inflammatory phenotypes in immune cells show enhanced osteoinductivity. More importantly, the interaction between hemostasis and the immune system should play a vital part in bone regeneration by determining both fibrin structure and bone healing microenvironment. Coagulants-triggered inflammation could, in turn, facilitate coagulation cascades, which form positive feedback to amplify both processes. Meanwhile, anti-coagulants neutralize coagulation and inhibit inflammation and thereby control the coagulation and inflammation to prevent thrombosis. The balance between coagulation–inflammation and anti-coagulation–anti-inflammation plays a determinant role in the fibrin structure and fibrinolysis process. The inflammation could be “quenched” gradually during this process, whereby a highly effective microenvironment for bone regeneration can be generated. Presently, there are limited biomaterial studies targeting the bone-healing hematoma, particularly the hemostasis–immune interplay. Considering this, this review summarizes the current materials for hemostasis and immunomodulation, and the critical role of the hemostasis–immune interaction in bone regeneration. It also proposes potential strategies to develop materials with the capacity to generate a highly effective bone healing hematoma, by modulating the hemostasis–immune interplay to maintain the balance between coagulation–inflammation and anti-coagulation–anti-inflammation.     

Emergency Treatment and Photoacoustic Assessment of Spinal Cord Injury Using Reversible Dual-Signal Transform-Based Selenium Antioxidant

Spinal cord injury (SCI), following explosive oxidative stress, causes an abrupt and irreversible pathological deterioration of the central nervous system. Thus, preventing secondary injuries caused by reactive oxygen species (ROS), as well as monitoring and assessing the recovery from SCI are critical for the emergency treatment of SCI. Herein, an emergency treatment strategy is developed for SCI based on the selenium (Se) matrix antioxidant system to effectively inhibit oxidative stress-induced damage and simultaneously real-time evaluate the severity of SCI using a reversible dual-photoacoustic signal (680 and 750 nm). Within the emergency treatment and photoacoustic severity assessment (ETPSA) strategy, the designed Se loaded boron dipyrromethene dye with a double hydroxyl group (Se@BDP-DOH) is simultaneously used as a sensitive reporter group and an excellent antioxidant for effectively eliminating explosive oxidative stress. Se@BDP-DOH is found to promote the recovery of both spinal cord tissue and locomotor function in mice with SCI. Furthermore, ETPSA strategy synergistically enhanced ROS consumption via the caveolin 1 (Cav 1)-related pathways, as confirmed upon treatment with Cav 1 siRNA. Therefore, the ETPSA strategy is a potential tool for improving emergency treatment and photoacoustic assessment of SCI.     

Converting 2D Nanofiber Membranes to 3D Hierarchical Assemblies with Structural and Compositional Gradients Regulates Cell Behavior

New methods are described for converting 2D electrospun nanofiber membranes to 3D hierarchical assemblies with structural and compositional gradients. Pore-size gradients are generated by tuning the expansion of 2D membranes in different layers with incorporation of various amounts of a surfactant during the gas-foaming process. The gradient in fiber organizations is formed by expanding 2D nanofiber membranes composed of multiple regions collected by varying rotating speeds of mandrel. A compositional gradient on 3D assemblies consisting of radially aligned nanofibers is prepared by dripping, diffusion, and crosslinking. Bone mesenchymal stem cells (BMSCs) on the 3D nanofiber assemblies with smaller pore size show significantly higher expression of hypoxia-related markers and enhanced chondrogenic differentiation compared to BMSCs cultured on the assemblies with larger pore size. The basic fibroblast growth factor gradient can accelerate fibroblast migration from the surrounding area to the center in an in vitro wound healing model. Taken together, 3D nanofiber assemblies with gradients in pore sizes, fiber organizations, and contents of signaling molecules can be used to engineer tissue constructs for tissue repair and build biomimetic disease models for studying disease biology and screening drugs, in particular, for interface tissue engineering and modeling.     

Multifunctional Hydrophobized Microparticles for Accelerated Wound Healing after Endoscopic Submucosal Dissection

Endoscopic submucosal dissection (ESD) provides strong therapeutic benefits for early gastrointestinal cancer as a minimally invasive treatment. However, there is currently no reliable treatment to prevent scar contracture resulting from ESD which may lead to cicatricial stricture. Herein, a multifunctional colloidal wound dressing to promote tissue regeneration after ESD is demonstrated. This sprayable wound dressing, composed of hydrophobized microparticles, exhibits the multifunctionality necessary for wound healing including tissue adhesiveness, blood coagulation, re‐epithelialization, angiogenesis, and controlled inflammation based on hydrophobic interaction with biological systems. An in vivo feasibility study using swine gastric ESD models reveals that this colloidal wound dressing suppresses fibrosis and accelerates wound healing. Multifunctional colloidal and sprayable wound dressings have an enormous therapeutic potential for use in a wide range of biomedical applications including accelerated wound healing after ESD, prevention of perforation, and the treatment of inflammatory diseases.     

Preparation of Superhydrophilic and Underwater Superoleophobic Nanofiber‐Based Meshes from Waste Glass for Multifunctional Oil/Water Separation

The deterioration of water resources due to oil pollution, arising from oil spills, industrial oily wastewater discharge, etc., urgently requires the development of novel functional materials for highly efficient water remediation. Recently, superhydrophilic and underwater superoleophobic materials have drawn significant attention due to their low oil adhesion and selective oil/water separation. However, it is still a challenge to prepare low‐cost, environmentally friendly, and multifunctional materials with superhydrophilicity and underwater superoleophobicity, which can be stably used for oil/water separation under harsh working conditions. Here, the preparation of nanofiber‐based meshes derived from waste glass through a green and sustainable route is demonstrated. The resulting meshes exhibit excellent performance in the selective separation of a wide range of oil/water mixtures. Importantly, these meshes can also maintain the superwetting property and high oil/water separation efficiency under various harsh conditions. Furthermore, the as‐prepared mesh can remove water‐soluble contaminants simultaneously during the oil/water separation process, leading to multifunctional water purification. The low‐cost and environmentally friendly fabrication, harsh‐environment resistance, and multifunctional characteristics make these nanofiber‐based meshes promising toward oil/water separation under practical conditions.     

A neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel enhances rat sciatic nerve regeneration

Nerve guidance conduit (NGC) is a potential alternative to autologous nerve for peripheral nerve regeneration. A promising therapeutic strategy is to modify the nerve guidance conduit intraluminal microenvironment using physical and/or chemical guidance cues. In this study, a neurotrophic peptide-functionalized self-assembling peptide nanofiber hydrogel that could promote PC12 cell adhesion, proliferation, and neuronal differentiation in vitro was prefilled in the lumen of a hollow chitosan tube (hCST) to accelerate axonal regeneration in a rat sciatic nerve defect model. The functionalized self-assembling peptide was developed by introducing a neurotrophic peptide (RGI, RGIDKRHWNSQ) derived from brain-derived neurotrophic factor (BDNF) to the C-terminus of the self-assembling peptide RADA16-I (Ac-(RADA)₄-CONH₂). Morphological, histological, electrophysiological, and functional analyses demonstrated that the RGI-functionalized, self-assembling, peptide nanofiber hydrogel RAD/RGI could produce a neurotrophic microenvironment that markedly improved axonal regeneration with enhanced re-myelination and motor functional recovery.

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Electrospun nanofibers as a platform for multifunctional,hierarchically organized nanocomposite

Nanofibers are ideally suited to form a scaffold where multi-functional components can be hierarchically organized. Development in electrospinning in terms of fiber construction and organization, materials selection and incorporation, and post-spinning modifications have pathed the way for future developments of advanced composite systems. A nanocomposite system with up to five distinct levels of organization can be constructed using electrospun fibers. At the first level is a composite nanofiber. The second level is a second layer of composite material coated over the core composite nanofiber. Surface modification of the nanofiber will give the third level. The fourth level of organization is by arranging the nanofibers to form an assembly. Finally at the last level, the nanofiber assembly can be encapsulated within a matrix or form a bulk structure of a pre-determined shape. Examples of how hierarchically organized multifunctional nanocomposite can be used in healthcare, environmental and defense and security is discussed.     

A Mussel‐Inspired Persistent ROS‐Scavenging,Electroactive, and Osteoinductive Scaffold Based on Electrochemical‐Driven In Situ Nanoassembly

Conductive polymers are promising for bone regeneration because they can regulate cell behavior through electrical stimulation; moreover, they are antioxidative agents that can be used to protect cells and tissues from damage originating from reactive oxygen species (ROS). However, conductive polymers lack affinity to cells and osteoinductivity, which limits their application in tissue engineering. Herein, an electroactive, cell affinitive, persistent ROS‐scavenging, and osteoinductive porous Ti scaffold is prepared by the on‐surface in situ assembly of a polypyrrole‐polydopamine‐hydroxyapatite (PPy‐PDA‐HA) film through a layer‐by‐layer pulse electrodeposition (LBL‐PED) method. During LBL‐PED, the PPy‐PDA nanoparticles (NPs) and HA NPs are in situ synthesized and uniformly coated on a porous scaffold from inside to outside. PDA is entangled with and doped into PPy to enhance the ROS scavenging rate of the scaffold and realize repeatable, efficient ROS scavenging over a long period of time. HA and electrical stimulation synergistically promote osteogenic cell differentiation on PPy‐PDA‐HA films. Ultimately, the PPy‐PDA‐HA porous scaffold provides excellent bone regeneration through the synergistic effects of electroactivity, cell affinity, and antioxidative activity of the PPy‐PDA NPs and the osteoinductivity of HA NPs. This study provides a new strategy for functionalizing porous scaffolds that show great promise as implants for tissue regeneration.     

Conductive Au nanowires regulated by silk fibroin nanofibers

Conductive Au-biopolymer composites have promising applications in tissue engineering such as nerve tissue regeneration. In this study, silk fibroin nanofibers were formed in aqueous solution by regulating silk self-assembly process and then used as template for Au nanowire fabrication. We performed the synthesis of Au seeds by repeating the seeding cycles for several times in order to increase the density of Au seeds on the nanofibers. After electroless plating, densely decorated Au seeds grew into irregularly shaped particles following silk nanofiber to fill the gaps between particles and finally form uniform continuous nanowires. The conductive property of the Au-silk fibroin nanowires was studied with current-voltage （I-V） measurement. A typical ohmic behavior was observed, which highlighted their potential applications in nerve tissue regeneration.     

Electrospun nanofibers: Work for medicine?

Attempts have been made to fabricate nanofibrous scaffolds to mimic the chemical composition and structural properties of the extracellular matrix (ECM) for tissue/organ replacement. Nanofiber scaffolds with various patterns have been successfully produced from synthetic and natural polymers through a relatively simple technique of electrospinning. The resulting patterns can mimic some of the diverse tissue-specific orientation and three-dimensional (3D) fibrous structures. Studies on cell-nanofiber interactions, including studies on stem cells, have revealed the importance of nanotopography on cell adhesion, proliferation and differentiation. Furthermore, clinical application of electrospun nanofibers including wound healing, tissue regeneration, drug delivery and stem cell therapy are highly feasible due to the ease and flexibility of fabrication of making nanofiber with this cost-effective method using electrospinning. In this review, we have highlighted the current state of the art and provided future perspectives on electrospun nanofiber in medical applications.     

Interplay of reactive oxygen species (ROS) and tissue engineering: a review on clinical aspects of ROS-responsive biomaterials

Reactive oxygen species (ROS) refers to the reactive molecules and free radicals of oxygen generated as the by-products of aerobic respiration. Historically, ROS are known as stress markers that are linked to the response of immune cell against microbial invasion, but recent discoveries suggest their role as secondary messengers in signal transduction and cell cycle. Tissue engineering (TE) techniques have the capabilities to harness such properties of ROS for the effective regeneration of damaged tissues. TE employs stem cells and biomaterial matrix, to heal and regenerate injured tissue and organ. During regeneration, one of the constraints is the unavailability of oxygen as proper vasculature is absent at the injured site. This creates hypoxic conditions at the site of regeneration. Hence, effective response against the stresses like hypoxia spurs the regeneration process. Contrary, hyperoxic condition may increase the risk of ROS stress at the site. TE tries to overcome these limitations with the new class of biomaterials that can sense such stresses and respond accordingly. This review endeavors to explain the role of ROS in stem cell proliferation and differentiation, which is a key component in regeneration. This compilation also highlights the new class of biomaterials that can overcome the hypoxic conditions during tissue regeneration along with emphasis on the ROS-responsive biomaterials and their clinical applications. Incorporating these biomaterials in scaffolds development holds huge potential in tissue or organ regeneration and even in drug delivery.

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Peptide-Functionalized Prussian Blue Nanomaterial for Antioxidant Stress and NIR Photothermal Therapy against Alzheimer's Disease

Excessive accumulations of reactive oxygen species (ROS) and amyloid-β (Aβ) protein are closely associated with the complex pathogenesis of Alzheimer's disease (AD). Therefore, approaches that synergistically exert elimination of ROS and dissociation of Aβ fibrils are effective therapeutic strategies for correcting the AD microenvironment. Herein, a novel near infrared (NIR) responsive Prussian blue-based nanomaterial (PBK NPs) is established with excellent antioxidant activity and photothermal effect. PBK NPs possess similar activities to multiple antioxidant enzymes, including superoxide dismutase, peroxidase, and catalase, which can eliminate massive ROS and relieve oxidative stress. Under the NIR irradiation, PBK NPs can generate local heat to disaggregate Aβ fibrils efficiently. By modifying CKLVFFAED peptide, PBK NPs display obvious targeting ability for blood–brain barrier penetration and Aβ binding. Furthermore, in vivo studies demonstrate that PBK NPs have outstanding ability to decompose Aβ plaques and alleviate neuroinflammation in AD mouse model. Overall, PBK NPs provide evident neuroprotection by reducing ROS levels and regulating Aβ deposition, and may accelerate the development of multifunctional nanomaterials for delaying the progression of AD.     

Mild Photothermal-Stimulation Based on Injectable and Photocurable Hydrogels Orchestrates Immunomodulation and Osteogenesis for High-Performance Bone Regeneration

A photoactivated bone scaffold integrated with minimally invasive implantation and mild thermal-stimulation capability shows great promise in the repair and regeneration of irregularly damaged bone tissues. Developing multifunctional photothermal biomaterials that can simultaneously serve as both controllable thermal stimulators and biodegradable engineering scaffolds for integrated immunomodulation, infection therapy, and impaired bone repair remains an enormous challenge. Herein, an injectable and photocurable hydrogel therapeutic platform (AMAD/MP) based on alginate methacrylate, alginate-graft-dopamine, and polydopamine (PDA)-functionalized Ti3C2 MXene (MXene@PDA) nanosheets is rationally designed for near-infrared (NIR)-mediated bone regeneration synergistic immunomodulation, osteogenesis, and bacterial elimination. The optimized AMAD/MP hydrogel exhibits favorable biocompatibility, osteogenic activity, and immunomodulatory functions in vitro. The proper immune microenvironment provided by AMAD/MP could further modulate the balance of M1/M2 phenotypes of macrophages, thereby suppressing reactive oxygen species-induced inflammatory status. Significantly, this multifunctional hydrogel platform with mild thermal stimulation efficiently attenuates local immune reactions and further promotes new bone formation without the addition of exogenous cells, cytokines, or growth factors. This work highlights the potential application of an advanced multifunctional hydrogel providing photoactivated on-demand thermal cues for bone tissue engineering and regenerative medicine.