Biomaterials For Bone Tissue Engineering Research Articles

Matrix Metalloproteinase-Responsive Hydrogel with On-Demand Release of Phosphatidylserine Promotes Bone Regeneration Through Immunomodulation.

Inflammation-responsive hydrogels loaded with therapeutic factors are effective biomaterials for bone tissue engineering and regenerative medicine. In this study, a matrix metalloproteinase (MMP)-responsive injectable hydrogel is constructed by integrating an MMP-cleavable peptide (pp) into a covalent tetra-armed poly-(ethylene glycol) (PEG) network for precise drug release upon inflammation stimulation. To establish a pro-regenerative environment, phosphatidylserine (PS) is encapsulated into a scaffold to form the PEG-pp-PS network, which could be triggered by MMP to release a large amount of PS during the early stage of inflammation and retain drug release persistently until the later stage of bone repair. The hydrogel is found to be mechanically and biologically adaptable to the complex bone defect area. In vivo and in vitro studies further demonstrated the ability of PEG-pp-PS to transform macrophages into the anti-inflammatory M2 phenotype and promote osteogenic differentiation, thus, resulting in new bone regeneration. Therefore, this study provides a facile, safe, and promising cell-free strategy on simultaneous immunoregulation and osteoinduction in bone engineering.

Generation of Pearl/Calcium Phosphate Composite Particles and Their Integration into Porous Chitosan Scaffolds for Bone Regeneration.

Bone tissue engineering using osteoconductive scaffolds holds promise for regeneration, with pearl powder gaining interest for its bioactive qualities. This study used freeze drying to create chitosan (CS) scaffolds with pearl/calcium phosphate (p/CaP) powders, mimicking bone tissue structurally and compositionally. Characterization included scanning electron microscopy (SEM) and mechanical testing. X-ray diffraction (XRD) Fourier-transform infrared-photoacoustic photo-acoustic sampling (FTIR-PAS), and FTIR- attenuated total reflectance (FTIR-ATR) were used to characterize p/CaP. In vitro tests covered degradation, cell activity, and SEM analysis. The scaffolds showed notable compressive strength and modulus enhancements with increasing p/CaP content. Porosity, ranging from 60% to 90%, decreased significantly at higher pearl/CaP ratios. Optimal cell proliferation and differentiation were observed with scaffolds containing up to 30 wt.% p/CaP, with 30 wt.% pearl powder and 30 wt.% p/CaP yielding the best results. In conclusion, pearl/calcium phosphate chitosan (p/CaP_CS) composite scaffolds emerged as promising biomaterials for bone tissue engineering, combining structural mimicry and favourable biological responses.

Calcium Phosphate Biomaterials for 3D Bioprinting in Bone Tissue Engineering.

Three-dimensional bioprinting is a promising technology for bone tissue engineering. However, most hydrogel bioinks lack the mechanical and post-printing fidelity properties suitable for such hard tissue regeneration. To overcome these weak properties, calcium phosphates can be employed in a bioink to compensate for the lack of certain characteristics. Further, the extracellular matrix of natural bone contains this mineral, resulting in its structural robustness. Thus, calcium phosphates are necessary components of bioink for bone tissue engineering. This review paper examines different recently explored calcium phosphates, as a component of potential bioinks, for the biological, mechanical and structural properties required of 3D bioprinted scaffolds, exploring their distinctive properties that render them favorable biomaterials for bone tissue engineering. The discussion encompasses recent applications and adaptations of 3D-printed scaffolds built with calcium phosphates, delving into the scientific reasons behind the prevalence of certain types of calcium phosphates over others. Additionally, this paper elucidates their interactions with polymer hydrogels for 3D bioprinting applications. Overall, the current status of calcium phosphate/hydrogel bioinks for 3D bioprinting in bone tissue engineering has been investigated.

Decoupling the roles of mechanical stretching and piezoelectrical stimulation in calcium signal mediated osteogenic differentiation of MSCs on biomimetic nanofibers

Piezoelectric materials implanted in vivo will be affected by physiological stress, leading to the generation of dynamic piezoelectrical signals. The cells identify both piezoelectrical and mechanical stimuli, and the way they behave is regulated through an electromechanical coupling process. Understanding the specific functions of individual stimulation on the osteogenic differentiation of mesenchymal stem cells (MSCs) would aid the development of ideal biomaterials for bone tissue engineering. In this work, by utilizing the controllable piezoelectric properties of polylactic acid materials, we prepared biomimetic piezoelectric poly (L-lactic acid) nanofibers and its non-piezoelectric isomer poly (D, l-lactide) nanofibers using the electrospinning technology. The dynamic piezoelectric and mechanical stimuli on the nanofibers were theoretically and experimentally investigated. A home-made in-situ mechanical loading platform was used to apply predetermined tensile loading on the nanofibers under cell culture conditions. The results indicated that piezo-potential ranging from 11 to 103 μV could be produced by cell adhesion forces varied between 1 and 15 nN, while mechanical loading ranging from 1 % to 15 % strain resulted in piezoelectrical signals in the magnitude of several volts. These piezoelectric signals could influence cell adhesion through enhancing cell aspect ratio and cell area. During the process of cell contraction and re-spreading caused by the mechanical loading, the piezoelectric signals were capable of accelerating the recovery of spreading and adhesion. Furthermore, individual piezoelectric and mechanical signals could modulate intracellular calcium signals, and significantly promote osteogenic differentiation of MSCs. Specifically, the mechanical stimulation could activate PIEZO signaling pathway, resulting in a greater upregulation of early osteogenic differentiation markers of Collagen type I and Bone morphogenetic protein-2 compared to the piezoelectric signal. However, the combination of the two stimuli could obviously and effectively enhance osteogenic differentiation of MSCs in a synergistic manner. These findings offer fresh understandings regarding the electromechanical influences in the process of bone tissue regeneration, which afford additional possibilities for optimizing piezoelectric biomaterials for biomedical applications in a more reasonable manner.

Fish waste-derived biomaterial as a support of zero waste and Sustainable Development Goals (SDGs)

Fish is a source of animal protein consumed by people worldwide. Its use for health and abundant fish production makes some countries or regions have high consumption compared to other animal protein sources. This study aims to review the potential of fish as a biomaterial to support zero waste and achieve the SDGs. This study reviews journals originating from Science Direct in narrative reviews of skin, scale, and bone waste from fish as biomaterials and the connection between zero waste efforts and SDGs. This study found that fish waste can be recycled into collagen, gelatin, hydroxyapatite, and calcium phosphate as biomaterials for bone tissue engineering, drug delivery, health, cosmetic, food, and pharmaceutical industries. It supports zero waste efforts and the achievement of SDGs in good health and well-being, responsible production and consumption, and decent work and economic growth.

Bioactivity properties of hydroxyapatite/clay nanocomposites

The need for bioactive and non-toxic biomaterials is on a high demand in tissue engineering applications nowadays. Hydroxyapatite (HAp) is the chief constituent of teeth and bones in mammas. One of the major challenges with the use of HAp in engineering application is its brittleness and to overcome this, it’s important to react it with a material that can enhanced it’s fragility. To this end, HAp and HAp/clay nanocomposites were developed via wet chemical process to mimic natural HAp and to equally confer special properties such as mechanical properties, high surface area, crystallinity, high porosity, and biocompatibility on the biomaterial. The functional groups properties of the as-prepared nanocomposites analyzed by FT-IR showed that the HAp and clay posed reactive centers such as Al–Al–OH, Si–Si–OH, Si–O, PO43−, –OH, and Si–O–Al. The XRD results confirmed the formation of HAp/clay nanocomposite, while SEM and TEM images showed the morphologies of the prepared nanocomposites to be round shape particles. Besides, EDX result revealed the Ca/P ratio of HAp and HAp-C to be lower than that of stoichiometric ratio (1.67) which implies the presence of K, Na, Ca, Mg, Si and Al in the HAp/clay nanocomposite. The mechanical properties of the apatite were greatly enhanced by the addition of clay. The physiological behaviour of the fabricated apatite composites in saline solution showed steady increase in the values of the saline pH of the various biomolecules until day 5 and became fairly constant at day 7 with pH range of 7.30–7.38. Though the saline solution was acidic at the beginning due to dissolved carbon dioxide, the pH of the saline solution containing the nanocomposites gradually became neutral and fairly alkaline over time as a result of the presence of Lewis basis structures in the composites which helps in neutralizing the acidic solution. Furthermore, proliferation of apatites particles onto the surface of the nanocomposites was observed after treatment with simulated body fluids (SBF) media for 7 days. Thus, HAp/clay nanocomposites can be useful biomaterials in bone tissue engineering.

The development of magnesium-based biomaterials in bone tissue engineering: A review.

Bone regeneration is a vital clinical challenge in massive or complicated bone defects. Recently, bone tissue engineering has come to the fore to meet the demand for bone repair with various innovative materials. However, the reported materials usually cannot satisfy the requirements, such as ideal mechanical and osteogenic properties, as well as biocompatibility at the same time. Mg-based biomaterials have considerable potential in bone tissue engineering owing to their excellent mechanical strength and biosafety. Moreover, the biocompatibility and osteogenic activity of Mg-based biomaterials have been the research focuses in recent years. The main limitation faced in the applications of Mg-based biomaterials is rapid degradation, which can produce excessive Mg2+ and hydrogen, affecting the healing of the bone defect. In order to overcome the limitations, researchers have explored several ways to improve the properties of Mg-based biomaterials, including alloying, surface modification with coatings, and synthesizing other composite materials to control the degradation rate upon implantation. This article reviewed the osteogenic mechanism and requirement for appropriate degradation rate and focused on current progress in the biomedical use of Mg-based biomaterials to inspire more clinical applications of Mg in bone regeneration in the future.

Type 2 Diabetes Mellitus Mediated Oxidative Stress in Bone Tissues and Novel Challenges for Biomaterials

AbstractType 2 diabetes mellitus is a chronic metabolic disease which can adversely affect the skeletal system, causing detrimental bone effects such as bone quality deterioration, loss of bone strength, increased fracture risk, and impaired bone healing. One of the major mechanisms is the increase in T2DM‐induced oxidative stress which results in an imbalance in bone remodeling and affects bone metabolism and bone regeneration. Recently, ROS‐scavenging biomaterials have been identified as a type of promising therapeutic substance to alleviate oxidative stress in tissue microenvironment. The aim of this review is to elaborate T2DM mediated oxidative stress in bone tissues and current application of ROS‐scavenging biomaterials in bone tissue engineering which provides a novel insight into biomaterials in diabetic bone tissue.

Ion incorporation into bone grafting materials.

The use of biomaterials in regenerative medicine has expanded to treat various disorders caused by trauma or disease in orthopedics and dentistry. However, the treatment of large and complex bone defects presents a challenge, leading to a pressing need for optimized biomaterials for bone repair. Recent advances in chemical sciences have enabled the incorporation of therapeutic ions into bone grafts to enhance their performance. These ions, such as strontium (for bone regeneration/osteoporosis), copper (for angiogenesis), boron (for bone growth), iron (for chemotaxis), cobalt (for B12 synthesis), lithium (for osteogenesis/cementogenesis), silver (for antibacterial resistance), and magnesium (for bone and cartilage regeneration), among others (e.g., zinc, sodium, and silica), have been studied extensively. This review aims to provide a comprehensive overview of current knowledge and recent developments in ion incorporation into biomaterials for bone and periodontal tissue repair. It also discusses recently developed biomaterials from a basic design and clinical application perspective. Additionally, the review highlights the importance of precise ion introduction into biomaterials to address existing limitations and challenges in combination therapies. Future prospects and opportunities for the development and optimization of biomaterials for bone tissue engineering are emphasized.

Sodium alginate/Hydroxyapatite/nanocellulose composites: Synthesis and Potentials for bone tissue engineering

Sodium alginate/hydroxyapatite/Nano cellulose (SA/HA/NC) nanocomposite films that possess good biocompatibility for bone tissue engineering are prepared by a simple solution casting. HA is one of the most frequently used bioceramic materials to achieve a high biocompatibility. The bionanocomposite films are analysed by XRD, SEM, EDAX and FTIR studies. XRD confirms the existence of fillers in the polymer. FTIR spectrum shows the different functional modes in the bionanocomposite films. The morphology of fillers and bionanocomposite films are obtained through SEM. The inclusion of NC with different concentrations into the biopolymer film improves the tensile strength. As a result, the loading of 5 wt % of NC and 10 wt% of HA in the SA polymer shows high tensile strength when compared to the pure SA, SA filled with 10 wt% of HA and SA loaded with 10 wt% of HA and inclusion of NC (0.5 and 2.5 wt%). The tensile strength (TS) of bionanocomposite film with 10 wt % of HA is increased by 17%. TS of bionanocomposite film with 0.5 and 2.5 wt% of NC is increased by 177 and 277%, whereas TS of bionanocomposite film loaded 5 wt% of NC is increased by 331%. The swelling, biodegradation and biomineralization tests suggest that this bionanocomposite films are hopeful biomaterials for bone tissue engineering.

Ion—modified optimization of smart scaffolds in bone tissue regeneration

Bioactive glasses and Calcium Phosphate bioceramics have emerged as promising scaffold biomaterials for bone tissue engineering. These materials possess inherent osteoinductive properties that work to create a more suitable environment for bone tissue formation. Additionally, these scaffolds exhibit dissolution properties when submerged in physiological fluids in vivo and therefore can release different ions. Incorporating therapeutic ion-modifiers that have independently demonstrated their osteogenic favorability to these scaffolds can further increase environmental suitability. This review discusses the favorable properties of bioactive glasses and Calcium Phosphate bioceramics in the context of Bone Tissue Engineering as well as potential incorporable metal ion-modifiers.

The use of waste bones of rabbitfish (Siganus sp.) for the synthesis of hydroxyapatite

This study obtained hydroxyapatite (HA) material by extracting waste bones from rabbitfish (Siganus sp.). The fish bones used are obtained from the waste bones of rabbitfish (Siganus sp.); besides being readily available in nature, they also reduce unwanted environmental impacts. X-ray fluorescence (XRF) and scanning electron microscopy (SEM) observations were used to analyze the hydroxyapatite (HA) produced by the sintering process. Samples produced at sintering temperatures of 800 °C, 850 °C, 900 °C, 950 °C, and 1000 °C had stoichiometric molar ratios of (Ca/P) that were, respectively, 1.728, 1.875, 1.759, 1.758, and 1.696. These results are consistent with the hydroxyapatite stoichiometric ratio (Ca/P = 1.67), and SEM was used to examine the measurement morphology of hydroxyapatite. This study reveals that bone waste from rabbitfish can be a source of biomaterials for bone tissue engineering.

Structural and biological evaluation of novel vanadium/Yttrium co-doped hydroxyapatite for bone tissue engineering applications

Hydroxyapatite (HA) is widely used in various medical fields due to its exceptional bioactivity, bio-affinity, and biocompatibility. However, the potential of biomaterials co-doped with metal ions for specific biomedical applications remains underexplored. In this study, we modified the HA structure by introducing vanadium (V) and yttrium (Y) to enhance its physicochemical and biological properties. V-Y co-doped HA (V-Y:HA) samples were prepared by the wet precipitation method using a reflux condensation setup with three different concentrations (0.005 M, 0.01 M, and 0.02 M) of V and Y. The addition of V and Y significantly influenced the biochemical properties and crystal structure of HA. X-ray diffraction (XRD) analysis revealed a modified crystal structure and the presence of the β-tricalcium phosphate (β -TCP) phase in the sample with a higher V concentration. V and Y incorporation resulted in smaller crystallite sizes and noticeable changes in lattice parameters. Scanning electron microscopy (SEM) images displayed sphere-like morphology with extensive aggregation. Fourier-transform infrared spectroscopy (FT-IR) and Raman analysis confirmed the presence of functional groups and phosphate vibrational modes in V-Y:HA samples. X-ray photoelectron spectroscopy (XPS) revealed the ionic and oxide forms of vanadium and the electronic states of yttrium. The as-prepared samples exhibited excellent mechanical strength, reduced porosity, and improved hemocompatibility compared to pure HA. The V-Y:HA sample with a higher V concentration demonstrated enhanced antibacterial activity against P. aeruginosa and S. aureus. In-vitro bioactivity assessment after 21 days revealed enhanced apatite formation on the surface of HA and V-Y:HA materials. These findings suggest that the novel V-Y:HA nanomaterials have great potential as biomaterials for bone tissue engineering and related applications.

Sustainable Sources of Raw Materials for Additive Manufacturing of Bone-Substituting Biomaterials.

The need for sustainable development has never been more urgent, as the world continues to struggle with environmental challenges, such as climate change, pollution, and dwindling natural resources. The use of renewable and recycled waste materials as a source of raw materials for biomaterials and tissue engineering is a promising avenue for sustainable development. Although tissue engineering has rapidly developed, the challenges associated with fulfilling the increasing demand for bone substitutes and implants remain unresolved, particularly as the global population ages. This review provides an overview of waste materials, such as eggshells, seashells, fish residues, and agricultural biomass, that can be transformed into biomaterials for bone tissue engineering. While the development of recycled metals is in its early stages, the use of probiotics and renewable polymers to improve the biofunctionalities of bone implants is highlighted. Despite the advances of additive manufacturing (AM), studies on AM waste-derived bone-substitutes are limited. It is foreseeable that AM technologies can provide a more sustainable alternative to manufacturing biomaterials and implants. The preliminary results of eggshell and seashell-derived calcium phosphate and rice husk ash-derived silica can likely pave the way for more advanced applications of AM waste-derived biomaterials for sustainably addressing several unmet clinical applications.

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.

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.

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.

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.