Stiffness-tunable biomaterials provide a good extracellular matrix environment for axon growth and regeneration

Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.

Unleashing the Potential of Electroactive Hybrid Biomaterials and Self‑Powered Systems for Bone Therapeutics

The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical phenomena have been well recognized as critical biophysical factors in bone remodeling and regeneration.Inspired by bioelectricity,electrical stimulation has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix,thereby accelerating bone regeneration.With ongoing advances in biomaterials and energy-harvesting techniques,electroactive biomaterials and self-powered systems have been considered biomimetic approaches to ensure functional recovery by recapitulating the natural electrophysiological microenvironment of healthy bone tissue.In this review,we first introduce the role of bioelectricity and the endogenous electric field in bone tissue and summarize different techniques to electrically stimulate cells and tissue.Next,we highlight the latest progress in exploring electroactive hybrid biomaterials as well as self-powered systems such as triboelectric and piezoelectric-based nanogenerators and photovoltaic cell-based devices and their implementation in bone tissue engineering.Finally,we emphasize the significance of simulating the target tissue’s electrophysiological microenvironment and propose the opportunities and challenges faced by electroactive hybrid biomaterials and self-powered bioelectronics for bone repair strategies.

Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical disability.Thus,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord injury.Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional recovery.Although the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans.This article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were analyzed.Thus,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

Biomimetic natural biomaterials for tissue engineering and regenerative medicine:new biosynthesis methods,recent advances,and emerging applications

Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative medicine.In contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix(ECM).Additionally,such materials have mechanical adaptability,micro-structure interconnectivity,and inherent bioactivity,making them ideal for the design of living implants for specific applications in TE and regenerative medicine.This paper provides an overview for recent progress of biomimetic natural biomaterials(BNBMs),including advances in their preparation,functionality,potential applications and future challenges.We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM.Moreover,we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications.Finally,we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.

Biomaterials and tissue engineering in traumatic brain injury:novel perspectives on promoting neural regeneration

Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the introduction of applications based on biochemistry and cell molecules, and discuss the emerging role of biomaterials in promoting neural regeneration. Further, we summarize the adaptive biomaterials infused with exosomes produced from stem cells and stem cells themselves for the treatment of traumatic brain injury. Finally, we present the main limitations of biomaterials for the treatment of traumatic brain injury and offer insights into their future potential.

Magnesium-based biomaterials for coordinated tissue repair:A comprehensive overview of design strategies,advantages,and challenges

Magnesium-based biomaterials(MBMs)are one of the most promising materials for tissue engineering due to their unique mechanical properties and excellent functional properties.This review describes the development,advantages,and challenges of MBMs for biomedical applications,especially for tissue repair and regeneration.The history of the use of MBMs from the beginning of the 20th century is traced,and the transformative advances in contemporary applications of MBMs in areas such as orthopedics and cardiovascular surgery are emphasized.The review also provides insight into the signaling pathways affected by MBMs,such as the PI3K/Akt and RANKL/RANK/OPG pathways,which are critical for osteogenesis and angiogenesis.The review advocates that future research should focus on optimizing alloy compositions,surface modification and exploring innovative technologies such as 3D printing to improve the efficacy of MBMs in complex tissue repair.The potential of MBMs to tissue engineering and regenerative medicine is significant,urging further exploration and interdisciplinary collaboration to maximize their therapeutic effects.

Biomaterials and emerging technologies for tissue engineering and in vitro models

The latest advances in the field of biomaterials have opened new avenues for scientific breakthroughs in tissue engineer-ing which greatly contributed for the successful translation of tissue engineering products into the market/clinics.Bio-materials are easily processed to become similar to natural extracellular matrix,making them ideal temporary supports for mimicking the three-dimensional(3D)microenvironment required for maintaining the adequate cell/tissue functions both in vitro and in vivo^([1]).

Mechanobiomaterials:Mechanics-Guided Design of Epicardial Patch for Treating

In recent years,the field of mechanomaterials has emerged at the interface of mechanics,materials science,biology,medicine and data science,where materials are proactively designed or programmed to achieve targeted functionalities by leveraging the fundamental mechanics principles and force-geometry-property relationships.In the biological context,one may likewise introduce mechanobiomaterials as a field with the following goals:(1)proactive design or programming of materials for precisely mediating biomechanical environment of living systems for tissue repair/restoration;(2)proactive control/programming of living systems themselves by an external field via force-structure-function relationships.Here,we will discuss an example of research in mechanobiomaterials on using mechanics to guide the design of acellular epicardial patches for the treatment of myocardial infarction.This technology aims to employ a biocompatible material patch to help reverse left ventricular remodeling and restore heart function after myocardial infarction by increasing the mechanical integrity of damaged heart tissues.However,its application is currently limited by widely scattered therapeutic efficacy.Here,we develop a biomechanics-based simulation platform that allows us to test,design and optimize the performance of an epicardial patch.We show that the widely scattered therapeutic efficacy of this technology can be attributed to a“pre-strain sensitivity”caused by attaching an elastic patch to a dynamically beating heart.To mitigate this challenge,we introduce a viscoelastic epicardial patch,designed at the so-called‘gel point’of the material,that effectively accommodates the cyclic deformation of the myocardium.This then leads to the fabrication and experimentally validated epicardial patch that outperforms all existing ones in restoring heart function after both acute and subacute myocardial infarction in rats.Our study also demonstrates the potential of employing viscoelastic interfaces for better integration of synthetic materials with biological tissues.

A Review on Silk Fibroin as a Biomaterial in Tissue Engineering

Regenerative medicine progress is based on the development of cell and tissue bioengineering. One of the aims of tissue engineering is the development of scaffolds, which should substitute the functions of the replaced organ after their implantation into the body. The tissue engineering material must meet a range of requirements, including biocompatibility, mechanical strength, and elasticity. Furthermore, the materials have to be attractive for cell growth: stimulate cell adhesion, migration, proliferation and differentiation. One of the natural biomaterials is silk and its component (silk fibroin). An increasing number of scientists in the world are studying silk and silk fibroin. The purpose of this review article is to provide information about the properties of natural silk (silk fibroin), as well as its manufacture and clinical application of each configuration of silk fibroin in medicine. Materials and research methods. Actual publications of foreign authors on resources PubMed, Medline, E-library have been analyzed. The selection criteria were materials containing information about the structure and components of silk, methods of its production in nature. This article placed strong emphasis on silk fibroin, the ways of artificial modification of it for use in various sphere of medicine.

Modulating immune responses for enhanced cell therapies:The dual role of multi-scale biomaterials

The efficacy of cell therapy is compromised by the suboptimal survival and function of transplanted cells,which can be partly attributed to uncontrolled immunomodulation.To address this issue,the dual role of biomaterials in assisting immune activation and evasion can be used to fine-tune immune responses and improve the efficacy and safety of cell therapy.Herein,we summarize different methods used to engineer therapeutic cells with biomaterials across multiple spatial scales and review how biomaterials assist in immune activation or evasion in cell therapy based on a discussion of the effects of biomaterials on endogenous immune cells.We also discuss the appealing features of biomaterials that polarize immune responses toward type 1 or type 2 immunity.In future studies,the biophysical and biochemical properties of biomaterials could be better leveraged for immunomodulatory purposes to fuel prominent improvements in cell therapy,and the relevant regulatory mechanisms should be investigated in a more systematic and in-depth manner.

Topology optimization of microstructure and selective laser meltingfabrication for metallic biomaterial scaffolds

The precise design and fabrication of biomaterial scaffolds is necessary to provide a systematic study for bone tissue engineering. Biomaterial scaffolds should have sufficient stiffness and large porosity. These two goals generally contradict since larger porosity results in lower mechanical properties. To seek the microstructure of maximum stiffness with the constraint of volume fraction by topology optimization method, algorithms and programs were built to obtain 2D and 3D optimized microstructure and then they were transferred to CAD models of STL format. Ti scaffolds with 30% volume fraction were fabricated using a selective laser melting （SLM） technology. The architecture and pore shape in the metallic biomaterial scaffolds were relatively precise reproduced and the minimum mean pore size was 231μm. The accurate fabrication of intricate microstructure has verified that the SLM process is suitable for fabrication of metallic biomaterial scaffolds.

MOLECULAR ENGINEERING STUDIES ON NONTHROMBOGENIC BIOMATERIALS——A NOVEL CLASS OF NONTHROMBOGENIC BIOMATERIALS WITH ZWITTERIONIC STRUCTURE OF CARBOXYBETAINES

N,N-dimethyl-N-methacryloyloxyethyl-N-carboxyethyl ammonium(DMMCA)was graft-copolymerized onto thesurface of segmented poly(ether urethane)(SPEU)and PE film.The carboxybetaine structure on SPEU and PE filmsurfaces was confirmed by ATR-FTIR,XPS and water contact angle measurements.Through the experiments with plateletadhesion and protein adhesion assay in vitro,the two materials studied,including poly-DMMCA gel,all show excellentnonthrombogenicity.This confirms once again that the zwitterionic molecular structure on the surfaces of materials isessential for improving their nonthrombogenicity and biocompatibility.

SYNTHETI C STUDIES ON BLOOD COMPATIBLE BIOMATERIALS Ⅳ. SYNTHESIS, CHARACTERIZATION AND ANTITHROMBOGENICITY OF POLY-[N, N'( p,p-OXYDIPHENYLENE)] PYROMELLI-TIMIDE-POLYDIMETHYLDIPHENYLSILOXANE SEGMENTED COPOLYMER

A novel class of aromatic polyimide-silicone segmented copolymer was synthesized with α, ω-bis (γ-aminopropyl) polydimethyldiphenylsiloxane (APMPS) as a silicone segment precursor, from which the segmented polyamic acid-b-silicone intermediate could be prepared simply with DMF as solvent. The segmented copolymer displays microphase separation and exhibits improved antithrombogenicity, which depends mainly upon both the content level and the DP of the silicone segment. Thermal stability and mechanical property of the copolymer are between that of the aromatic polyimide and the silicone, and also relate to both the content level and the DP of the silicone segment.

Review of magnesium-based biomaterials and their applications

In biomedical applications,the conventionally used metallic materials,including stainless steel,Co-based alloys and Ti alloys,often times exhibit unsatisfactory results such as stress shielding and metal ion releases.Secondary surgical operation(s)usually become inevitable to prevent long term exposure of body with the toxic implant contents.The metallic biomaterials are being revolutionized with the development of biodegradable materials including several metals,alloys,and metallic glasses.As such,the nature of metallic biomaterials are transformed from the bioinert to bioactive and multi-biofunctional(anti-bacterial,anti-proliferation,anti-cancer,etc.).Magnesium-based biomaterials are candidates to be used as new generation biodegradable metals.Magnesium(Mg)can dissolve in body fluid that means the implanted Mg can degrade during healing process,and if the degradation is controlled it would leave no debris after the completion of healing.Hence,the need for secondary surgical operation(s)for the implant removal could be eliminated.Besides its biocompatibility,the inherent mechanical properties of Mg are very similar to those of human bone.Researchers have been working on synthesis and characterization of Mg-based biomaterials with a variety of composition in order to control the degradation rate of Mg since uncontrolled degradation could result in loss of mechanical integrity,metal contamination in the body and intolerable hydrogen evolution by tissue.It was observed that the applied methods of synthesis and the choice of components affect the characteristics and performance of the Mg-based biomaterials.Researchers have synthesized many Mg-based materials through several synthesis routes and investigated their mechanical properties,biocompatibility and degradation behavior through in vitro,in vivo and in silico studies.This paper is a comprehensive review that compiles,analyses and critically discusses the recent literature on the important aspects of Mg-based biomaterials.

Conductive Biomaterials as Bioactive Wound Dressing for Wound Healing and Skin Tissue Engineering

Conductive biomaterials based on conductive polymers,carbon nanomaterials,or conductive inorganic nanomaterials demonstrate great potential in wound healing and skin tissue engineering,owing to the similar conductivity to human skin,good antioxidant and antibacterial activities,electrically controlled drug delivery,and photothermal effect.However,a review highlights the design and application of conductive biomaterials for wound healing and skin tissue engineering is lacking.In this review,the design and fabrication methods of conductive biomaterials with various structural forms including film,nanofiber,membrane,hydrogel,sponge,foam,and acellular dermal matrix for applications in wound healing and skin tissue engineering and the corresponding mechanism in promoting the healing process were summarized.The approaches that conductive biomaterials realize their great value in healing wounds via three main strategies(electrotherapy,wound dressing,and wound assessment)were reviewed.The application of conductive biomaterials as wound dressing when facing different wounds including acute wound and chronic wound(infected wound and diabetic wound)and for wound monitoring is discussed in detail.The challenges and perspectives in designing and developing multifunctional conductive biomaterials are proposed as well.

Implant biomaterials: A comprehensive review

Appropriate selection of the implant biomaterial is a key factor for long term success of implants. The biologic environment does not accept completely any material so to optimize biologic performance, implants should be selected to reduce the negative biologic response while maintaining adequate function. Every clinician should always gain a thorough knowledge about thedifferent biomaterials used for the dental implants. This article makes an effort to summarize various dental biomaterials which were used in the past and as well as the latest material used now.

Advances in regenerative therapies for spinal cord injury:a biomaterials approach

Spinal cord injury results in the permanent loss of function, causing enormous personal, social and economic problems. Even though neural regeneration has been proven to be a natural mech- anism, central nervous system repair mechanisms are ineffective due to the imbalance of the inhibitory and excitatory factors implicated in neuroregeneration. Therefore, there is growing re- search interest on discovering a novel therapeutic strategy for effective spinal cord injury repair. To this direction, cell-based delivery strategies, biomolecule delivery strategies as well as scaf- fold-based therapeutic strategies have been developed with a tendency to seek for the answer to a combinatorial approach of all the above. Here we review the recent advances on regenerativel neural engineering therapies for spinal cord injury, aiming at providing an insight to the most promising repair strategies, in order to facilitate future research conduction.

Magnesium-based biomaterials as emerging agents for bone repair and regeneration:from mechanism to application

Magnesium(Mg)is the fourth most abundant element in the human body and is important in terms of specific osteogenesis functions.Here,we provide a comprehensive review of the use of magnesium-based biomaterials(MBs)in bone reconstruction.We review the history of MBs and their excellent biocompatibility,biodegradability and osteopromotive properties,highlighting them as candidates for a new generation of biodegradable orthopedic implants.In particular,the results reported in the field-specific literature(280 articles)in recent decades are dissected with respect to the extensive variety of MBs for orthopedic applications,including Mg/Mg alloys,bioglasses,bioceramics,and polymer materials.We also summarize the osteogenic mechanism of MBs,including a detailed section on the physiological process,namely,the enhanced osteogenesis,promotion of osteoblast adhesion and motility,immunomodulation,and enhanced angiogenesis.Moreover,the merits and limitations of current bone grafts and substitutes are compared.The objective of this review is to reveal the strong potential of MBs for their use as agents in bone repair and regeneration and to highlight issues that impede their clinical translation.Finally,the development and challenges of MBs for transplanted orthopedic materials are discussed.

Role and prospects of regenerative biomaterials in the repair of spinal cord injury

Axonal junction defects and an inhibitory environment after spinal cord injury seriously hinder the regeneration of damaged tissues and neuronal functions. At the site of spinal cord injury, regenerative biomaterials can fill cavities, deliver curative drugs, and provide adsorption sites for transplanted or host cells. Some regenerative biomaterials can also inhibit apoptosis, inflammation and glial scar formation, or further promote neurogenesis, axonal growth and angiogenesis. This review summarized a variety of biomaterial scaffolds made of natural, synthetic, and combined materials applied to spinal cord injury repair. Although these biomaterial scaffolds have shown a certain therapeutic effect in spinal cord injury repair, there are still many problems to be resolved, such as product standards and material safety and effectiveness.

Recent advances in smart stimuli-responsive biomaterials for bone therapeutics and regeneration

Bone defects combined with tumors, infections, or other bone diseases are challenging in clinical practice. Autologous and allogeneic grafts are two main traditional remedies, but they can cause a series of complications. To address this problem,researchers have constructed various implantable biomaterials. However, the original pathological microenvironment of bone defects, such as residual tumors, severe infection, or other bone diseases, could further affect bone regeneration. Thus, the rational design of versatile biomaterials with integrated bone therapy and regeneration functions is in great demand. Many strategies have been applied to fabricate smart stimuli-responsive materials for bone therapy and regeneration, with stimuli related to external physical triggers or endogenous disease microenvironments or involving multiple integrated strategies. Typical external physical triggers include light irradiation, electric and magnetic fields, ultrasound, and mechanical stimuli. These stimuli can transform the internal atomic packing arrangements of materials and affect cell fate, thus enhancing bone tissue therapy and regeneration. In addition to the external stimuli-responsive strategy, some specific pathological microenvironments, such as excess reactive oxygen species and mild acidity in tumors, specific p H reduction and enzymes secreted by bacteria in severe infection, and electronegative potential in bone defect sites, could be used as biochemical triggers to activate bone disease therapy and bone regeneration.Herein, we summarize and discuss the rational construction of versatile biomaterials with bone therapeutic and regenerative functions. The specific mechanisms, clinical applications, and existing limitations of the newly designed biomaterials are also clarified.