Biomaterials For Tissue Engineering Research Articles

Advances and Prospects in Materials for Craniofacial Bone Reconstruction.

The craniofacial region is composed of 23 bones, which provide crucial function in keeping the normal position of brain and eyeballs, aesthetics of the craniofacial complex, facial movements, and visual function. Given the complex geometry and architecture, craniofacial bone defects not only affect the normal craniofacial structure but also may result in severe craniofacial dysfunction. Therefore, the exploration of rapid, precise, and effective reconstruction of craniofacial bone defects is urgent. Recently, developments in advanced bone tissue engineering bring new hope for the ideal reconstruction of the craniofacial bone defects. This report, presenting a first-time comprehensive review of recent advances of biomaterials in craniofacial bone tissue engineering, overviews the modification of traditional biomaterials and development of advanced biomaterials applying to craniofacial reconstruction. Challenges and perspectives of biomaterial development in craniofacial fields are discussed in the end.

Characterization of Chitosan Films Modified Using Caffeic Acid and a Neutralization Process.

In the context of the growing interest in biopolymer-based materials for various applications, this study aimed to enhance the properties of chitosan (CS, a derivative of chitin) films by incorporating caffeic acid, a polyphenol compound known for its multiple health benefits. The objective was to improve the mechanical parameters of the resulting films, including surface roughness and elasticity. CS was combined with caffeic acid and then underwent a neutralization process. The modified films exhibited potential for use in soft tissue engineering, where increased elasticity and surface roughness are desirable characteristics. The main methods employed to evaluate the structure and properties of the films included mechanical analysis, infrared spectroscopy, scanning electron microscopy, atomic force microscopy, thermogravimetric analysis, contact angle measurement, and swelling behavior. The study's main findings revealed significant alterations in the mechanical properties and surface morphology of the films. The main conclusions drawn from the study suggest that interactions between caffeic acid and CS hold promise for the development of advanced biomaterials in medicine, tissue engineering, and cosmetic formulations. However, a deeper understanding of these interactions is necessary to optimize the material properties and unlock their full potential.

Decellularized umbilical cord stroma in tissue engineering and regenerative medicine: a systematic review

Despite great progress in the field of biomaterials for tissue engineering and regenerative medicine, the high requirements placed on artificial matrices (matrices, carriers, scaffolds) are the reason for the ongoing search for natural or synthetic extracellular matrix mimetics. Among such materials, decellularized umbilical cord (UC) stroma appears to be very attractive – it has a high content of hyaluronic acid, cytokines, and growth factors, and there are no ethical restrictions for its production. Decellularized UC stroma has been found to promote cartilage, liver tissue and nerve tissue repair, as well as wound healing. The review critically analyzes and summarizes published data on the ability of decellularized UC stroma to maintain the necessary conditions for adhesion, migration, differentiation and functional activity of adherent cells, thus stimulating the internal (physiological) regenerative potential of tissues. Literature was searched for in the following electronic databases: Medline/PubMed (www/ncbi. nlm.nih.gov/pubmed), Cochrane library (https://www.cochrane.org), and eLIBRARY/Russian Science Citation Index (https://www.elibrary.ru). Inclusion criteria were the presence of biomaterials obtained from decellularized human UC stroma. Exclusion criteria for papers included research objects as decellularized umbilical cord vessels (veins and arteries) and umbilical cord cell cultures. Twenty-five original articles in English and Russian were selected for analysis of the products obtained, their applications, decellularization methods and research results. The review also discusses the prospects for decellularized umbilical cord in medicine.

Collective Organization Behaviors of Multi‐Cell Systems Induced by Engineered ECM‐Cell Mechanical Coupling

AbstractCells in vivo are surrounded by fibrous extracellular matrix (ECM), which can mediate the propagation of active cellular forces through stressed fiber bundles and regulate various biological processes. However, the mechanisms for multi‐cellular organization and collective dynamics induced by cell‐ECM mechanical couplings, which are crucial for the development of novel ECM‐based biomaterial for cell manipulation and biomechanical applications, remain poorly understood. Herein, the authors design an in vitro quasi‐3D experimental system and demonstrate a transition between spreading and aggregating in collective organizational behaviors of discrete multi‐cellular systems, induced by engineered ECM‐cell mechanical coupling, with the observed phenomena and underlying mechanisms differing fundamentally from those of cell monolayers. During the process of collective cell organization, the collagen substrate undergoes reconstruction into a dense fiber network structure, which is correlated with local cellular density and consistent with observed enhanced cells' motility; and the weakening of fiber bundle formation within the hydrogel reduces cells’ movement. Moreover, cells can respond to the curvature and shape of the original cell population and form different aggregation patterns. These results elucidate important physical factors involved in collective cell organization and provide important references for potential applications of biomaterials in new therapies and tissue engineering.

Leveraging the Recent Advancements in GelMA Scaffolds for Bone Tissue Engineering: An Assessment of Challenges and Opportunities.

The field of bone tissue engineering has seen significant advancements in recent years. Each year, over two million bone transplants are performed globally, and conventional treatments, such as bone grafts and metallic implants, have their limitations. Tissue engineering offers a new level of treatment, allowing for the creation of living tissue within a biomaterial framework. Recent advances in biomaterials have provided innovative approaches to rebuilding bone tissue function after damage. Among them, gelatin methacryloyl (GelMA) hydrogel is emerging as a promising biomaterial for supporting cell proliferation and tissue regeneration, and GelMA has exhibited exceptional physicochemical and biological properties, making it a viable option for clinical translation. Various methods and classes of additives have been used in the application of GelMA for bone regeneration, with the incorporation of nanofillers or other polymers enhancing its resilience and functional performance. Despite promising results, the fabrication of complex structures that mimic the bone architecture and the provision of balanced physical properties for both cell and vasculature growth and proper stiffness for load bearing remain as challenges. In terms of utilizing osteogenic additives, the priority should be on versatile components that promote angiogenesis and osteogenesis while reinforcing the structure for bone tissue engineering applications. This review focuses on recent efforts and advantages of GelMA-based composite biomaterials for bone tissue engineering, covering the literature from the last five years.

Research Progress of Design Drugs and Composite Biomaterials in Bone Tissue Engineering.

Bone, like most organs, has the ability to heal naturally and can be repaired slowly when it is slightly injured. However, in the case of bone defects caused by diseases or large shocks, surgical intervention and treatment of bone substitutes are needed, and drugs are actively matched to promote osteogenesis or prevent infection. Oral administration or injection for systemic therapy is a common way of administration in clinic, although it is not suitable for the long treatment cycle of bone tissue, and the drugs cannot exert the greatest effect or even produce toxic and side effects. In order to solve this problem, the structure or carrier simulating natural bone tissue is constructed to control the loading or release of the preparation with osteogenic potential, thus accelerating the repair of bone defect. Bioactive materials provide potential advantages for bone tissue regeneration, such as physical support, cell coverage and growth factors. In this review, we discuss the application of bone scaffolds with different structural characteristics made of polymers, ceramics and other composite materials in bone regeneration engineering and drug release, and look forward to its prospect.

Travelling through the Natural Hierarchies of Type I Collagen with X-rays: From Tendons of Cattle, Horses, Sheep and Pigs.

Type I collagen physiological scaffold for tissue regeneration is considered one of the widely used biomaterials for tissue engineering and medical applications. It is hierarchically organized: five laterally staggered molecules are packed within fibrils, arranged into fascicles and bundles. The structural organization is correlated to the direction and intensity of the forces which can be loaded onto the tissue. For a tissue-specific regeneration, the required macro- and microstructure of a suitable biomaterial has been largely investigated. Conversely, the function of multiscale structural integrity has been much less explored but is crucial for scaffold design and application. In this work, collagen was extracted from different animal sources with protocols that alter its structure. Collagen of tendon shreds excised from cattle, horse, sheep and pig was structurally investigated by wide- and small-angle X-ray scattering techniques, at both molecular and supramolecular scales, and thermo-mechanically with thermal and load-bearing tests. Tendons were selected because of their resistance to chemical degradation and mechanical stresses. The multiscale structural integrity of tendons' collagen was studied in relation to the animal source, anatomic location and source for collagen extraction.

Stimuli-responsive hydrogels: smart state of-the-art platforms for cardiac tissue engineering.

Biomedicine and tissue regeneration have made significant advancements recently, positively affecting the whole healthcare spectrum. This opened the way for them to develop their applications for revitalizing damaged tissues. Thus, their functionality will be restored. Cardiac tissue engineering (CTE) using curative procedures that combine biomolecules, biomimetic scaffolds, and cells plays a critical part in this path. Stimuli-responsive hydrogels (SRHs) are excellent three-dimensional (3D) biomaterials for tissue engineering (TE) and various biomedical applications. They can mimic the intrinsic tissues' physicochemical, mechanical, and biological characteristics in a variety of ways. They also provide for 3D setup, adequate aqueous conditions, and the mechanical consistency required for cell development. Furthermore, they function as competent delivery platforms for various biomolecules. Many natural and synthetic polymers were used to fabricate these intelligent platforms with innovative enhanced features and specialized capabilities that are appropriate for CTE applications. In the present review, different strategies employed for CTE were outlined. The light was shed on the limitations of the use of conventional hydrogels in CTE. Moreover, diverse types of SRHs, their characteristics, assembly and exploitation for CTE were discussed. To summarize, recent development in the construction of SRHs increases their potential to operate as intelligent, sophisticated systems in the reconstruction of degenerated cardiac tissues.

MXene functionalized collagen biomaterials for cardiac tissue engineering driving iPSC-derived cardiomyocyte maturation

Electroconductive biomaterials are gaining significant consideration for regeneration in tissues where electrical functionality is of crucial importance, such as myocardium, neural, musculoskeletal, and bone tissue. In this work, conductive biohybrid platforms were engineered by blending collagen type I and 2D MXene (Ti3C2Tx) and afterwards covalently crosslinking; to harness the biofunctionality of the protein component and the increased stiffness and enhanced electrical conductivity (matching and even surpassing native tissues) that two-dimensional titanium carbide provides. These MXene platforms were highly biocompatible and resulted in increased proliferation and cell spreading when seeded with fibroblasts. Conversely, they limited bacterial attachment (Staphylococcus aureus) and proliferation. When neonatal rat cardiomyocytes (nrCMs) were cultured on the substrates increased spreading and viability up to day 7 were studied when compared to control collagen substrates. Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) were seeded and stimulated using electric-field generation in a custom-made bioreactor. The combination of an electroconductive substrate with an external electrical field enhanced cell growth, and significantly increased cx43 expression. This in vitro study convincingly demonstrates the potential of this engineered conductive biohybrid platform for cardiac tissue regeneration.

Repairing gastric ulcer with hyaluronic acid/extracellular matrix composite through promoting M2-type polarization of macrophages

The treatment of gastric ulcer and perforation using synthetic and biomaterials has been a clinical challenge. In this work, a drug-carrying layer of hyaluronic acid was combined with a gastric submucosal decellularized extracellular matrix called gHECM. The regulation of macrophage polarization by the extracellular matrix's components was then investigated. This work proclaims how gHECM responds to inflammation and aids in the regeneration of the gastric lining by altering the phenotype of surrounding macrophages and stimulating the body's whole immune response. In a nutshell, gHECM promotes tissue regeneration by changing the phenotype of macrophages around the site of injury. In particular, gHECM reduces the production of pro-inflammatory cytokines, decreases the percentage of M1 macrophages, and further encourages differentiation of macrophage subpopulation to the M2 phenotype and the release of anti-inflammatory cytokines, which could block the NF-κB pathway. Activated macrophages are capable of immediately delivering through spatial barriers, modulating the peripheral immune system, influencing the inflammatory microenvironment, and ultimately promoting the recovery of inflammation and healing of ulcers. They contribute to the secreted cytokines that act on local tissues or enhance the chemotactic ability of macrophages through paracrine secretion. In this study, we focused on the immunological regulatory network of macrophage polarization to further develop the mechanisms behind this process. Nevertheless, the signaling pathways involved in this process need to be further explored and identified. We think that our research will encourage more investigation into how the decellularized matrix affects immune modulation and will help the decellularized matrix perform better as a new class of natural biomaterials for tissue engineering.

The Design and Developments of Protein‐Polysaccharide Biomaterials for Corneal Tissue Engineering

AbstractCorneal blindness is explained by a large reduction in vision loss caused by acute and chronic corneal diseases and/or disorders. Due to the severe unavailability of donor corneas, immune rejection, and the side effects of keratoprosthesis (KPro), vision‐impaired patients are often unable to restore their vision. Corneal tissue engineering appears to be a promising method using natural polymers made from different layers of corneal cells such as epithelium, stroma, and endothelium or full tissue equivalents. Proteins and polysaccharides are able to mimic the chemical composition of the native extracellular matrix (ECM), which has been extensively studied for corneal tissue engineering. Additionally, protein‐based materials are highly favored in corneal regenerative therapy as they have the proper cell‐binding sites for cell adhesion, corneal innervation regeneration, and oxidative stress suppression, while polysaccharide‐based materials can also promote cell proliferation and adhesion as well as ocular permeability. Herein, a comprehensive review of various biomaterials based on natural proteins (fibrin, fibrinogen, silk fibroin, collagen, gelatin, and serum albumin) and polysaccharides (chitin, chitosan, hyaluronic acid, alginate, cellulose, and gellan gum) for corneal tissue engineering are provided. The protein‐polysaccharide biomaterials are mainly used in the form of hydrogels, films, scaffolds, sutures, eye drops, nanocarriers, and nanocapsules to treat ocular diseases that cause blindness, such as corneal wounds, corneal ulcers, Goldenhar syndrome, corneal endothelium and stroma defects, corneal neovascularization, etc. In this review, insight is provided into recent developments in the areas of biomaterial design, cross‐linking strategy, corneal cell selection, and frontiers that are expected to offer researchers support and creativity in the development of corneal regenerative medicine.

Calcium Phosphate-Based Nanomaterials: Preparation, Multifunction, and Application for Bone Tissue Engineering.

Calcium phosphate is the main inorganic component of bone. Calcium phosphate-based biomaterials have demonstrated great potential in bone tissue engineering due to their superior biocompatibility, pH-responsive degradability, excellent osteoinductivity, and similar components to bone. Calcium phosphate nanomaterials have gained more and more attention for their enhanced bioactivity and better integration with host tissues. Additionally, they can also be easily functionalized with metal ions, bioactive molecules/proteins, as well as therapeutic drugs; thus, calcium phosphate-based biomaterials have been widely used in many other fields, such as drug delivery, cancer therapy, and as nanoprobes in bioimaging. Thus, the preparation methods of calcium phosphate nanomaterials were systematically reviewed, and the multifunction strategies of calcium phosphate-based biomaterials have also been comprehensively summarized. Finally, the applications and perspectives of functionalized calcium phosphate biomaterials in bone tissue engineering, including bone defect repair, bone regeneration, and drug delivery, were illustrated and discussed by presenting typical examples.

Composites of Bacillus megaterium H16 derived poly-3-hydroxybutyrate as a biomaterial for skin tissue engineering

Composite films of Bacillus megaterium H16 derived PHB with 1%Poly-L-lactic acid (PLLA), 1%Poly-ε-caprolactone (PCL), and 0.3 % graphene nanoplatelets (GNP) were produced by solvent cast method. The composite films were characterized by SEM, DSC-TGA, XRD, and ATR-FTIR. The ultrastructure of PHB and its composites depicted an irregular surface morphology with pores after the evaporation of chloroform. The GNPs were seen to be integrated inside the pores. The B. megaterium H16 derived-PHB and its composites demonstrated good biocompatibility which was evaluated in vitro on HaCaT and L929 cells by MTT assay. The cell viability was best for PHB followed by PHB/PLLA/PCL > PHB/PLLA/GNP > PHB/PLLA. PHB and its composites were highly hemocompatible as it resulted in <1 % hemolysis. The PHB/PLLA/PCL and PHB/PLLA/GNP composites can serve as ideal biomaterials for skin tissue engineering.

Novel Bioactive Glass/Graphene Oxide-Coated Surgical Sutures for Soft Tissue Regeneration.

The combination of a commercially available PGLA (poly[glycolide-co-l-lactide]), 90:10% suture material with bioactive bioglass nanopowders (BGNs) and graphene oxide (GO)-doped BGNs offers new opportunities for the clinical application of biomaterials in soft tissue engineering. In the present experimental work, we demonstrate that GO-doped melt-derived BGNs were synthesized via the sol-gel process. After that, novel GO-doped and undoped BGNs were used to coat resorbable PGLA surgical sutures, thereby imparting bioactivity, biocompatibility, and accelerated wound healing properties to the sutures. Stable and homogeneous coatings on the surface of the sutures were achieved using an optimized vacuum sol deposition method. The phase composition, morphology, elemental characteristics, and chemical structure of uncoated and BGNs- and BGNs/GO-coated suture samples were characterized using Fourier transform infrared spectroscopy, field emission scanning electron microscopy, associated with elemental analysis, and knot performance test. In addition, in vitro bioactivity tests, biochemical tests, and in vivo tests were performed to examine the role of BGNs and GO on the biological and histopathological properties of the coated suture samples. The results indicated that the formation of BGNs and GO was enhanced significantly on the suture surface, which allowed for enhanced fibroblast attachment, migration, and proliferation and promoted the secretion of the angiogenic growth factor to speed up wound healing. These results confirmed the biocompatibility of BGNs- and BGNs/GO-coated suture samples and the positive effect of BGNs on the behavior of L929 fibroblast cells and also showed for the first time the possibility that cells can adhere and proliferate on the BGNs/GO-coated suture samples, especially in an in vivo environment. Resorbable surgical sutures with bioactive coatings, such as those prepared herein, can be an attractive biomaterial not only for hard tissue engineering but also for clinical applications in soft tissue engineering.

Facilitation of Osteogenic Differentiation of hASCs on PEDOT:PSS/MXene Composite Sponge with Electrical Stimulation

Innovations in biomedical tissue engineering are on the increase as many researchers look for ways to develop biological scaffolds for cells. Studies have shown that the application of external force and electrical stimulation (ES) promotes stem cell chondrogenic and osteogenic differentiation. Therefore, bioscaffolds sensitive to external stimuli can not only influence the cell behavior with their native physical and biochemical properties but also act as a mediator receiving an outside-in signal to alter the cellular activities under specific conditions. For the first time, the synthetic polymer poly(3,4-ethylene dioxythiophene):polystyrene sulfonate) (PEDOT:PSS) was combined with a two-dimensional, nanoconducting material, titanium carbide (MXene, Ti3C2X3), to prepare three-dimensional (3D) conductive scaffolds. Some studies have shown that MXene has good biocompatibility, osteoinductivity, and bone regeneration activity. The PEDOT:PSS/MXene scaffold was applied to the osteogenic differentiation of hASCs, and ES was used to enhance the osteogenic differentiation. The results showed that the conductive scaffold had low cytotoxicity to hASCs, which could grow and migrate in the 3D scaffold. In addition, osteogenic-specific gene expression significantly differed when the ES was applied. We propose that this PEDOT:PSS/MXene scaffold may serve as a platform for the study of osteogenic differentiation of stem cells with ES and may potentially be ex vivo fabricated as a tissue engineering construct for studying other modes of other ESs such as direct current, capacitive, or inductive coupling in a 3D environment.

The Role of Extracellular Matrix (ECM) Adhesion Motifs in Functionalised Hydrogels.

To create functional tissue engineering scaffolds, biomaterials should mimic the native extracellular matrix of the tissue to be regenerated. Simultaneously, the survival and functionality of stem cells should also be enhanced to promote tissue organisation and repair. Hydrogels, but in particular, peptide hydrogels, are an emerging class of biocompatible scaffolds which act as promising self-assembling biomaterials for tissue engineering and regenerative therapies, ranging from articular cartilage regeneration at joint defects, to regenerative spinal cord injury following trauma. To enhance hydrogel biocompatibility, it has become imperative to consider the native microenvironment of the site for regeneration, where the use of functionalised hydrogels with extracellular matrix adhesion motifs has become a novel, emerging theme. In this review, we will introduce hydrogels in the context of tissue engineering, provide insight into the complexity of the extracellular matrix, investigate specific adhesion motifs that have been used to generate functionalised hydrogels and outline their potential applications in a regenerative medicine setting. It is anticipated that by conducting this review, we will provide greater insight into functionalised hydrogels, which may help translate their use towards therapeutic roles.

Advanced applications of strontium-containing biomaterials in bone tissue engineering.

Strontium (Sr) and strontium ranelate (SR) are commonly used therapeutic drugs for patients suffering from osteoporosis. Researches have showed that Sr can significantly improve the biological activity and physicochemical properties of materials in vitro and in vivo. Therefore, a large number of strontium containing biomaterials have been developed for repairing bone defects and promoting osseointegration. In this review, we provide a comprehensive overview of Sr-containing biomaterials along with the current state of their clinical use. For this purpose, the different types of biomaterials including calcium phosphate, bioactive glass, and polymers are discussed and provided future outlook on the fabrication of the next-generation multifunctional and smart biomaterials.

Protease-degradable hydrogels with multifunctional biomimetic peptides for bone tissue engineering.

Mimicking bone extracellular matrix (ECM) is paramount to develop novel biomaterials for bone tissue engineering. In this regard, the combination of integrin-binding ligands together with osteogenic peptides represents a powerful approach to recapitulate the healing microenvironment of bone. In the present work, we designed polyethylene glycol (PEG)-based hydrogels functionalized with cell instructive multifunctional biomimetic peptides (either with cyclic RGD-DWIVA or cyclic RGD-cyclic DWIVA) and cross-linked with matrix metalloproteinases (MMPs)-degradable sequences to enable dynamic enzymatic biodegradation and cell spreading and differentiation. The analysis of the intrinsic properties of the hydrogel revealed relevant mechanical properties, porosity, swelling and degradability to engineer hydrogels for bone tissue engineering. Moreover, the engineered hydrogels were able to promote human mesenchymal stem cells (MSCs) spreading and significantly improve their osteogenic differentiation. Thus, these novel hydrogels could be a promising candidate for applications in bone tissue engineering, such as acellular systems to be implanted and regenerate bone or in stem cells therapy.

Magnetic and Biocompatible Polyurethane Nanofiber Biomaterial for Tissue Engineering.

Recruitment of endothelial cells to cardiovascular device surfaces could solve issues of thrombosis, neointimal hyperplasia, and restenosis. Since current targeting strategies are often nonspecific, new technologies to allow for site-specific cell localization and capture in vivo are needed. The development of cytocompatible superparamagnetic iron oxide nanoparticles has allowed for the use of magnetism for cell targeting. In this study, a magnetic polyurethane (PU)-2205 stainless steel (2205-SS) nanofibrous composite biomaterial was developed through analysis of composite sheets and application to stent-grafts. The PU nanofibers provide strength and elasticity while the 2205-SS microparticles provide ferromagnetic properties. Sheets were electrospun at mass ratios of 0-4:1 (2205-SS:PU) and stent-grafts with magnetic or nonmagnetic stents were coated at the optimal ratio of 2:1. These composite materials were characterized by microscopy, mechanical testing, a sessile drop test, magnetic field measurement, magnetic cell capture assays, and cytocompatibility after 14 days of culturing with endothelial cells. Results of this study show that an optimal ratio of 2:1 2205-SS:PU results in a hydrophobic material that balanced mechanical and magnetic properties and was cytocompatible up to 14 days. Significant cell capture required a thicker material of 0.5 mm thickness. Stent-grafts fabricated from a magnetic coating and a magnetic stent demonstrated uniform cell capture throughout the device surface. This novel biomaterial exhibits a combination of mechanical and magnetic properties that enables magnetic capture of cells and other therapeutic agents for vascular and other tissue engineering applications.

Application of Composite Biomaterials from Chinese Herbal Medicine in the Field of Bone Tissue Engineering

Research into bone tissue engineering is increasing with advances in biomaterials. Natural products of plant origin have exciting therapeutic effects through multiple targets. The purpose of this article is to review the outstanding performance of herbal-derived natural products in bone tissue engineering. We have categorized herbal-derived natural products that exert different effects in bone tissue engineering into osteogenic, vascular, chondrogenic, anti-inflammatory and antibacterial. Natural products of plant origin are readily available and can be combined with biomaterials as bioactive molecules to complement each other and provide additional opportunities for bone tissue engineering. Finally, we discuss the challenges and opportunities for the development of plant composite biomaterials for bone tissue engineering and highlight emerging strategies in this field.