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.

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.

Bone tissue engineering via nanostructured calcium phosphate biomaterials and stem cells

Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate （CAP） biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review： nanostructured calcium phosphate cement （CPC）; nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/ morphology, differentiation and in vivo bone regeneration. Several trends can be seen： （i） nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; （ii） the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; （iii） nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; （iv） combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and （v） cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments.

Biomaterial–Related Cell Microenvironment in Tissue Engineering and Regenerative Medicine

An appropriate cell microenvironment is key to tissue engineering and regenerative medicine.Revealing the factors that influence the cell microenvironment is a fundamental research topic in the fields of cell biology,biomaterials,tissue engineering,and regenerative medicine.The cell microenvironment consists of not only its surrounding cells and soluble factors,but also its extracellular matrix(ECM)or nearby external biomaterials in tissue engineering and regeneration.This review focuses on six aspects of bioma-terial-related cell microenvironments:①chemical composition of materials,②material dimensions and architecture,③material-controlled cell geometry,④effects of material charges on cells,⑤matrix stiff-ness and biomechanical microenvironment,and⑥surface modification of materials.The present chal-lenges in tissue engineering are also mentioned,and eight perspectives are predicted.

Innovations in 3D bioprinting and biomaterials for liver tissue engineering:Paving the way for tissue-engineered liver

The liver is a pivotal organ that maintains internal homeostasis and actively participates in multiple physiological processes.Liver tissue engineering(LTE),by which in vitro biomimetic liver models are constructed,serves as a platform for disease research,drug screening,and cell replacement therapies.3D bioprinting is used in tissue engineering to create microenvironments that closely mimic authentic tissues with carefully selected functional biomaterials.Ideal functional biomaterials exhibit characteristics such as high biocompatibility,mechanical strength,flexibility,processability,and tunable degradability.Biomaterials can be categorized into natural and synthetic biomaterials,each with its own advantages and limitations,and their combinations serve as a primary source of 3D bioprinting materials.It is noteworthy that the liver decellularized extracellular matrix(dECM),obtained by removing cellular components from tissues,possesses traits such as bioactivity,biocompatibility,and non-immunogenicity,making it a common choice among functional biomaterials.Furthermore,crosslinking of biomaterials significantly impacts the mechanical strength,physicochemical properties,and cellular behavior of the printed structures.This review covers the current utilization of biomaterials in LTE,focusing on natural and synthetic biomaterials as well as the selection and application of crosslinking methods.The aim is to enhance the fidelity of in vitro liver tissue models by providing a comprehensive coverage of functional biomaterials,thereby establishing a versatile platform for tissue-engineered livers.

Dental-derived stem cells in tissue engineering:the role of biomaterials and host response

Dental-derived stem cells(DSCs)are attractive cell sources due to their easy access,superior growth capacity and low immunogenicity.They can respond to multiple extracellular matrix signals,which provide biophysical and biochemical cues to regulate the fate of residing cells.However,the direct transplantation of DSCs suffers from poor proliferation and differentiation toward functional cells and low survival rates due to local inflammation.Recently,elegant advances in the design of novel biomaterials have been made to give promise to the use of biomimetic biomaterials to regulate various cell behaviors,including proliferation,differentiation and migration.Biomaterials could be tailored with multiple functionalities,e.g.,stimuli-responsiveness.There is an emerging need to summarize recent advances in engineered biomaterials-mediated delivery and therapy of DSCs and their potential applications.Herein,we outlined the design of biomaterials for supporting DSCs and the host response to the transplantation.

Engineering multifunctional bioactive citrate-based biomaterials for tissue engineering

Developing bioactive biomaterials with highly controlled functions is crucial to enhancing their applications in regenerative medicine.Citrate-based polymers are the few bioactive polymer biomaterials used in biomedicine because of their facile synthesis,controllable structure,biocompatibility,biomimetic viscoelastic mechanical behavior,and functional groups available for modification.In recent years,various multifunctional designs and biomedical applications,including cardiovascular,orthopedic,muscle tissue,skin tissue,nerve and spinal cord,bioimaging,and drug or gene delivery based on citrate-based polymers,have been extensively studied,and many of them have good clinical application potential.In this review,we summarize recent progress in the multifunctional design and biomedical applications of citrate-based polymers.We also discuss the further development of multifunctional citrate-based polymers with tailored properties to meet the requirements of various biomedical applications.

Polymeric biomaterials-based tissue engineering for wound healing: a systemic review

Background:Biomaterials are vital products used in clinical sectors as alternatives to several biological macromolecules for tissue engineering techniques owing to their numerous beneficial properties,including wound healing.The healing pattern generally depends upon the type of wounds,and restoration of the skin on damaged areas is greatly dependent on the depth and severity of the injury.The rate of wound healing relies on the type of biomaterials being incorporated for the fabrication of skin substitutes and their stability in in vivo conditions.In this review,a systematic literature search was performed on several databases to identify the most frequently used biomaterials for the development of successful wound healing agents against skin damage,along with their mechanisms of action.Method:The relevant research articles of the last 5 years were identified,analysed and reviewed in this paper.The meta-analysis was carried out using PRISMA and the search was conducted in major scientific databases.The research of the most recent 5 years,from 2017-2021 was taken into consideration.The collected research papers were inspected thoroughly for further analysis.Recent advances in the utilization of natural and synthetic biomaterials(alone/in combination)to speed up the regeneration rate of injured cells in skin wounds were summarised.Finally,23 papers were critically reviewed and discussed.Results:In total,2022 scholarly articles were retrieved from databases utilizing the aforementioned input methods.After eliminating duplicates and articles published before 2017,∼520 articles remained that were relevant to the topic at hand(biomaterials for wound healing)and could be evaluated for quality.Following different procedures,23 publications were selected as best fitting for data extraction.Preferred Reporting Items for Systematic Reviews and Meta-Analyses for this review illustrates the selection criteria,such as exclusion and inclusion parameters.The 23 recent publications pointed to the use of both natural and synthetic polymers in wound healing applications.Information related to wound type and the mechanism of action has also been reviewed carefully.The selected publication showed that composites of natural and synthetic polymers were used extensively for both surgical and burn wounds.Extensive research revealed the effects of polymer-based biomaterials in wound healing and their recent advancement.Conclusions:The effects of biomaterials in wound healing are critically examined in this review.Different biomaterials have been tried to speed up the healing process,however,their success varies with the severity of the wound.However,some of the biomaterials raise questions when applied on a wide scale because of their scarcity,high transportation costs and processing challenges.Therefore,even if a biomaterial has good wound healing qualities,it may be technically unsuitable for use in actual medical scenarios.All of these restrictions have been examined closely in this review.

Oxysterols as promising small molecules for bone tissue engineering: Systematic review

BACKGROUND Bone tissue engineering is an area of continued interest within orthopaedic surgery,as it promises to create implantable bone substitute materials that obviate the need for autologous bone graft.Recently,oxysterols–oxygenated derivatives of cholesterol-have been proposed as a novel class of osteoinductive small molecules for bone tissue engineering.Here,we present the first systematic review of the in vivo evidence describing the potential therapeutic utility of oxysterols for bone tissue engineering.AIM To systematically review the available literature examining the effect of oxysterols on in vivo bone formation.METHODS We conducted a systematic review of the literature following PRISMA guidelines.Using the PubMed/MEDLINE,Embase,and Web of Science databases,we queried all publications in the English-language literature investigating the effect of oxysterols on in vivo bone formation.Articles were screened for eligibility using PICOS criteria and assessed for potential bias using an expanded version of the SYRCLE Risk of Bias assessment tool.All full-text articles examining the effect of oxysterols on in vivo bone formation were included.Extracted data included:Animal species,surgical/defect model,description of therapeutic and control treatments,and method for assessing bone growth.Primary outcome was fusion rate for spinal fusion models and percent bone regeneration for critical-sized defect models.Data were tabulated and described by both surgical/defect model and oxysterol employed.Additionally,data from all included studies were aggregated to posit the mechanism by which oxysterols may mediate in vivo bone formation.RESULTS Our search identified 267 unique articles,of which 27 underwent full-text review.Thirteen studies(all preclinical)met our inclusion/exclusion criteria.Of the 13 included studies,5 employed spinal fusion models,2 employed critical-sized alveolar defect models,and 6 employed critical-sized calvarial defect models.Based upon SYRCLE criteria,the included studies were found to possess an overall“unclear risk of bias”;54%of studies reported treatment randomization and 38%reported blinding at any level.Overall,seven unique oxysterols were evaluated:20(S)-hydroxycholesterol,22(R)-hydroxycholesterol,22(S)-hydroxycholesterol,Oxy4/Oxy34,Oxy18,Oxy21/Oxy133,and Oxy49.All had statistically significant in vivo osteoinductive properties,with Oxy4/Oxy34,Oxy21/Oxy133,and Oxy49 showing a dose-dependent effect in some cases.In the eight studies that directly compared oxysterols to rhBMP-2-treated animals,similar rates of bone growth occurred in the two groups.Biochemical investigation of these effects suggests that they may be primarily mediated by direct activation of Smoothened in the Hedgehog signaling pathway.CONCLUSION Present preclinical evidence suggests oxysterols significantly augment in vivo bone formation.However,clinical trials are necessary to determine which have the greatest therapeutic potential for orthopaedic surgery patients.

Molecular Tissue Engineering:Concepts,Status and Challenge

Tissue engineering has confronted many difficulties mainly as follows:1)How to modulate the adherence,proliferation,and oriented differentiation of seed cells, especially that of stemcells. 2) Massive preparation and sustained controllable delivery of tissue inducing factors or plasmid DNA, such as growth factors, angiogenesis stimulators,and so on. 3) Development of 'intelligent biomimetic materials' as extracellular matrix with a good superficial and structural compatibility as well as biological activity to stimulate predictable, controllable and desirable responses under defined conditions.Molecular biology is currently one of the most exciting fields of research across life sciences,and the advances in it also bring a bright future for tissue engineering to overcome these difficulties.In recent years,tissue engineering benefits a lot from molecular biology.Only a comprehensive understanding of the involved ingredients of tissue engineering (cells,tissue inducing factors,genes,biomaterials) and the subtle relationships between them at molecular level can lead to a successful manipulation of reparative processes and a better biological substitute.Molecular tissue engineering,the offspring of the tissue engineering and molecular biology,has gained an increasing importance in recent years.It offers the promise of not simply replacing tissue,but improving the restoration.The studies presented in this article put forward this new concept for the first time and provide an insight into the basic principles,status and challenges of this emerging technology.

Biomaterial strategies for the application of reproductive tissue engineering

Human reproductive organs are of vital importance to the life of an individual and the reproduction of human populations.So far,traditional methods have a limited effect in recovering the function and fertility of reproductive organs and tissues.Thus,aim to replace and facilitate the regrowth of damaged or diseased tissue,various biomaterials are developed to offer hope to overcome these difficulties and help gain further research progress in reproductive tissue engineering.In this review,we focus on the biomaterials and their four main applications in reproductive tissue engineering:in vitro generation and culture of reproductive cells;development of reproductive organoids and models;in vivo transplantation of reproductive cells or tissues;and regeneration of reproductive tissue.In reproductive tissue engineering,designing biomaterials for different applications with different mechanical properties,structure,function,and microenvironment is challenging and important,and deserves more attention.

Recent advancements in applications of chitosan-based biomaterials for skin tissue engineering

The use of polymer based composites in the treatment of skin tissue damages,has got huge attention in clinical demand,which enforced the scientists to improve the methods of biopolymer designing in order to obtain highly efficient system for complete restoration of damaged tissue.In last few decades,chitosan-based biomaterials have major applications in skin tissue engineering due to its biocompatible,hemostatic,antimicrobial and biodegradable capabilities.This article overviewed the promising biological properties of chitosan and further discussed the various preparation methods involved in chitosan-based biomaterials.In addition,this review also gave a comprehensive discussion of different forms of chitosan-based biomaterials including membrane,sponge,nanofiber and hydrogel that were extensively employed in skin tissue engineering.This review will help to form a base for the advanced applications of chitosan-based biomaterials in treatment of skin tissue damages.

Chondroinductive/chondroconductive peptides and their-functionalized biomaterials for cartilage tissue engineering

The repair of articular cartilage defects is still challenging in the fields of orthopedics and maxillofacial surgery due to the avascular structure of articular cartilage and the limited regenerative capacity of mature chondrocytes.To provide viable treatment options,tremendous efforts have been made to develop various chondrogenically-functionalized biomaterials for cartilage tissue engineering.Peptides that are derived from and mimic the functions of chondroconductive cartilage extracellular matrix and chondroinductive growth factors,represent a unique group of bioactive agents for chondrogenic functionalization.Since they can be chemically synthesized,peptides bear better reproducibility,more stable efficacy,higher modifiability and yielding efficiency in comparison with naturally derived biomaterials and recombinant growth factors.In this review,we summarize the current knowledge in the designs of the chondroinductive/chondroconductive peptides,the underlying molecular mechanisms and their-functionalized biomaterials for cartilage tissue engineering.We also systematically compare their in-vitro and in-vivo efficacies in inducing chondrogenesis.Our vision is to stimulate the development of novel peptides and their-functionalized biomaterials for cartilage tissue engineering.

Evaluation of corneal cell growth on tissue engineering materials as artificial cornea scaffolds

The keratoprosthesis(KPro;artificial cornea)is a special refractive device to replace human cornea by using heterogeneous forming materials for the implantation into the damaged eyes in order to obtain a certain vision.The main problems of artificial cornea are the biocompatibility and stability of the tissue particularly in penetrating keratoplasty.The current studies of tissue-engineered scaffold materials through comprising composites of natural and synthetic biopolymers together have developed a new way to artificial cornea.Although a wide agreement that the long-term stability of these devices would be greatly improved by the presence of cornea cells,modification of keratoprosthesis to support cornea cells remains elusive.Most of the studies on corneal substrate materials and surface modification of composites have tried to improve the growth and biocompatibility of cornea cells which can not only reduce the stimulus of heterogeneous materials,but also more importantly continuous and stable cornea cells can prevent the destruction of collagenase.The necrosis of stroma and spontaneous extrusion of the device,allow for maintenance of a precorneal tear layer,and play the role of ensuring a good optical surface and resisting bacterial infection.As a result,improvement in corneal cells has been the main aim of several recent investigations;some effort has focused on biomaterial for its well biological properties such as promoting the growth of cornea cells.The purpose of this review is to summary the growth status of the corneal cells after the implantation of several artificial corneas.

Biomaterials for repair and regeneration of the cartilage tissue

The repair and regeneration of the diseases and damaged cartilage tissue are one of the most challenging issues in the field of tissue engineering and regenerative medicine. As the cartilage is a non-vascularized and comparatively acellular connective tissue, its ability to the self-restoration is limited to a large extent. Although there is a countless deal of experimental documents on this field, no quantifiable cure exists to bring back the healthy organization and efficacy of the impaired articular cartilage. Tissue reformative approaches have been of excessive curiosity in restoring injured cartilage. Bioengineering of the cartilage has progressed from the cartilage focal damages treatment to bioengineering tactics progress aiming the osteoarthritis procedures. The main focus of the present study is on the diverse potential development of strategies such as various categories of biomaterials applied in the reconstruction of the cartilage tissue.

Additive manufacturing of sustainable biomaterials for biomedical applications

Biopolymers are promising environmentally benign materials applicable in multifarious applications.They are especially favorable in implantable biomedical devices thanks to their excellent unique properties,including bioactivity,renewability,bioresorbability,biocompatibility,biodegradability and hydrophilicity.Additive manufacturing(AM)is a flexible and intricate manufacturing technology,which is widely used to fabricate biopolymer-based customized products and structures for advanced healthcare systems.Three-dimensional(3D)printing of these sustainable materials is applied in functional clinical settings including wound dressing,drug delivery systems,medical implants and tissue engineering.The present review highlights recent advancements in different types of biopolymers,such as proteins and polysaccharides,which are employed to develop different biomedical products by using extrusion,vat polymerization,laser and inkjet 3D printing techniques in addition to normal bioprinting and four-dimensional(4D)bioprinting techniques.It also incorporates the influence of nanoparticles on the biological and mechanical performances of 3D-printed tissue scaffolds,and addresses current challenges as well as future developments of environmentally friendly polymeric materials manufactured through the AMtechniques.Ideally,there is a need for more focused research on the adequate blending of these biodegradable biopolymers for achieving useful results in targeted biomedical areas.We envision that biopolymer-based 3D-printed composites have the potential to revolutionize the biomedical sector in the near future.

New paradigms in regenerative engineering:Emerging role of extracellular vesicles paired with instructive biomaterials

Mesenchymal stem cells(MSCs)have long been regarded as critical components of regenerative medicine strategies,given their multipotency and persistence in a variety of tissues.Recently,the specific role of MSCs in mediating regenerative outcomes has been attributed(in part)to secreted factors from transplanted cells,namely extracellular vesicles.This viewpoint manuscript highlights the promise of cell-derived extracellular vesicles as agents of regeneration,enhanced by synergy with appropriate biomaterials platforms.Extracellular vesicles are a potentially interesting regenerative tool to enhance the synergy between MSCs and biomaterials.As a result,we believe these technologies will improve patient outcomes through efficient therapeutic strategies resulting in predictable patient outcomes.

Silk fibroins modify the atmospheric low temperature plasma-treated poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) film for the application of cardiovascular tissue engineering

Tissue engineered scaffold is one of the hopeful therapies for the patients with organ or tissue damages. The key element for a tissue engineered scaffold material is high biocompatibility. Herein the poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) film was irradiated by the low temperature atmospheric plasma and then coated by the silk fibroins (SF). After plasma treatment, the surface of PHBHHx film became rougher and more hydrophilic than that of original film. The experiment of PHBHHx flushed by phosphate buffer solution (PBS) proves that the coated SF shows stronger immobilization on the plasma-treated film than that on the untreated film. The cell viability assay demonstrates that SF-coated PHBHHx films treated by the plasma significantly supports the proliferation and growth of the human smooth muscle cells (HSMCs). Furthermore, the scanning electron microscopy and hemotoylin and eosin (HE) staining show that HSMCs formed a cell sub-monolayer and secreted a large amount of extracellular matrix (ECM) on the films after one week's culture. The silk fibroins modify the plasma-treated PHBHHx film, providing a material potentially applicable in the cardiovascular tissue engi-neering.