Materials For Bone Tissue Engineering Research Articles

Enhancement of Bone Tissue Regeneration with Multi-Functional Nanoparticles by Coordination of Immune, Osteogenic, and Angiogenic Responses.

Inorganic nanoparticles are promising materials for bone tissue engineering due to their chemical resemblance to the native bone structure. However, most studies are unable to capture the entirety of the defective environment, providing limited bone regenerative abilities. Hence, this study aims to develop a multifunctional nanoparticle to collectively control the defective bone niche, including immune, angiogenic, and osteogenic systems. The nanoparticles, self-assembled by biomimetic mineralization and tannic acid (TA)-mediated metal-polyphenol network (MPN), are released sustainably after the incorporation within a gelatin cryogel. The released nanoparticles display a reduction in M1 macrophages by means of reactive oxygen species (ROS) elimination. Consequently, osteoclast maturation is also reduced, which is observed by the minimal formation of multinucleated cells (0.4%). Furthermore, the proportion of M2 macrophages, osteogenic differentiation, and angiogenic potential are consistently increased by the effects of magnesium from the nanoparticles. This orchestrated control of multiple systems influences the in vivo vascularized bone regeneration in which 80% of the critical-sized bone defect is regenerated with new bones with mature lamellar structure and arteriole-scale micro-vessels. Altogether, this study emphasizes the importance of the coordinated modulation of immune, osteogenic, and angiogenic systems at the bone defect site for robust bone regeneration.

Silver and magnesium co-doped β-TCP nanoparticles as potential materials for bone tissue engineering

Silver and magnesium co-doped β-TCP nanoparticles as potential materials for bone tissue engineering

Properties of Carbonated Hydroxyapatite-Based Scaffold from Oyster Shells Composited with Honeycomb and Polyethylene Oxide for Bone Tissue Engineering Applications

Scaffold Carbonated Hydroxyapatite/Honeycomb/Polyethylene Oxide (CHA/HCB/PEO) has been obtained by freeze-drying. The bioceramic CHA used in this study was synthesized from oyster shells using precipitation. HCB and PEO were added as reinforcement materials that affect the crystallographic properties of the scaffold. This study aimed to determine the characteristics of the scaffolds for bone tissue engineering. CHA and scaffolds were characterized using Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffractometer (XRD), and Scanning Electron Microscopy (SEM). FTIR spectra and XRD graphs confirmed that the CHA produced was B-type. FTIR spectra of the scaffold showed the presence of HCB and PEO in the scaffold, which means they were homogeneously bound in the scaffold solution. XRD test results show that scaffolds' crystallinity and crystallite size tends to decrease compared to CHA. This was good because they could make cells easier to proliferate. A small-scale pore structure (micropore) was also formed in the scaffold. The porosity and pore size of the scaffold were affected by the concentration of CHA. The presence of the micropores can increase the permeability of the scaffold and facilitate cell migration. Thus, the composition of CHA/HCB/PEO scaffolds can be a good candidate material in bone tissue engineering.

Numerical study on effect of process parameters on material extrusion 3D printing (ME3DP) for porous bone tissue engineering scaffolds

Bone tissue engineering (BTE) holds promise for treating bone defects, and 3D-printed porous scaffolds are pivotal for tissue regeneration. This study explores the impact of material extrusion 3D printing (ME3DP) process parameters (i.e., layer height and extrusion temperature) on 3D-printed porous scaffolds made of polyetherimide (PEI) material for BTE. The intricate relationships shaping scaffold dimensional accuracy, residual stresses, and warpage tendencies were unveiled using comprehensive numerical simulations. Our findings reveal that higher layer heights enhance dimensional stability, especially at lower printing temperatures, reducing maximum displacements. Consequently, lower layer heights lead to higher warpage critical values. This insight is instrumental in optimizing the material extrusion 3D printing (ME3DP) process, vital for precise net shape in BTE applications. Furthermore, residual stresses also revealed a correlation between higher printing temperatures and increased residual stresses. These findings emphasize the necessity of balancing material flow, printing temperature, and layer height for scaffold quality. Therefore, the right balance between precision and mechanical stability is critical for producing high-quality scaffolds that meet BTE requirements.

Simultaneous Regulation of the Mechanical/Osteogenic Capacity of Brushite Calcium Phosphate Cement by Incorporating with Poly(ethylene glycol) Dicarboxylic Acid.

Brushite calcium phosphate cement (brushite CPC) is a prospective bone repair material due to its ideal resorption rates in vivo. However, the undesirable mechanical property and bioactivity limited its availability in clinic application. To address this issue, incorporating polymeric additives has emerged as a viable solution. In this study, poly(ethylene glycol) dicarboxylic acid, PEG(COOH), was synthesized and employed as the polymeric additive. The setting behavior, anti-washout ability, mechanical property, degradation rate, and osteogenic capacity of brushite CPC were regulated by incorporating PEG(COOH). The incorporation of PEG(COOH) with carboxylic acid groups demonstrated a positive effect on both mechanical properties and osteogenic activity in bone repair. This study offers valuable insights and suggests a promising strategy for the development of materials in bone tissue engineering.

3D printed high-precision porous scaffolds prepared by fused deposition modeling induce macrophage polarization to promote bone regeneration

Macrophage-mediated bone immune responses significantly influence the repair of bone defects when utilizing tissue-engineered scaffolds. Notably, the scaffolds’ physical structure critically impacts macrophage polarization. The optimal pore size for facilitating bone repair remains a topic of debate due to the imprecision of traditional methods in controlling scaffold pore dimensions and spatial architecture. In this investigation, we utilized fused deposition modeling (FDM) technology to fabricate high-precision porous polycaprolactone (PCL) scaffolds, aiming to elucidate the impact of pore size on macrophage polarization. We assessed the scaffolds’ mechanical attributes and biocompatibility. Real-time quantitative reverse transcription polymerase chain reaction was used to detect the expression levels of macrophage-related genes, and enzyme linked immunosorbent assay for cytokine secretion levels. In vitro osteogenic capacity was determined through alkaline phosphatase and alizarin red staining. Our findings indicated that macroporous scaffolds enhanced macrophage adhesion and drove their differentiation towards the M2 phenotype. This led to the increased production of anti-inflammatory factors and a reduction in pro-inflammatory agents, highlighting the scaffolds’ immunomodulatory capabilities. Moreover, conditioned media from macrophages cultured on these macroporous scaffolds bolstered the osteogenic differentiation of bone marrow mesenchymal stem cells, exhibiting superior osteogenic differentiation potential. Consequently, FDM-fabricated PCL scaffolds, with precision-controlled pore sizes, present promising prospects as superior materials for bone tissue engineering, leveraging the regulation of macrophage polarization.

Performance of 3D printed porous polyetheretherketone composite scaffolds combined with nano-hydroxyapatite/carbon fiber in bone tissue engineering: a biological evaluation

Polyetheretherketone (PEEK) has been one of the most promising materials in bone tissue engineering in recent years, with characteristics such as biosafety, corrosion resistance, and wear resistance. However, the weak bioactivity of PEEK leads to its poor integration with bone tissues, restricting its application in biomedical fields. This research effectively fabricated composite porous scaffolds using a combination of PEEK, nano-hydroxyapatite (nHA), and carbon fiber (CF) by the process of fused deposition molding (FDM). The experimental study aimed to assess the impact of varying concentrations of nHA and CF on the biological performance of scaffolds. The incorporation of 10% CF has been shown to enhance the overall mechanical characteristics of composite PEEK scaffolds, including increased tensile strength and improved mechanical strength. Additionally, the addition of 20% nHA resulted in a significant increase in the surface roughness of the scaffolds. The high hydrophilicity of the PEEK composite scaffolds facilitated the in vitro inoculation of MC3T3-E1 cells. The findings of the study demonstrated that the inclusion of 20% nHA and 10% CF in the scaffolds resulted in improved cell attachment and proliferation compared to other scaffolds. This suggests that the incorporation of 20% nHA and 10% CF positively influenced the properties of the scaffolds, potentially facilitating bone regeneration. In vitro biocompatibility experiments showed that PEEK composite scaffolds have good biosafety. The investigation on osteoblast differentiation revealed that the intensity of calcium nodule staining intensified, along with an increase in the expression of osteoblast transcription factors and alkaline phosphatase activities. These findings suggest that scaffolds containing 20% nHA and 10% CF have favorable properties for bone induction. Hence, the integration of porous PEEK composite scaffolds with nHA and CF presents a promising avenue for the restoration of bone defects using materials in the field of bone tissue engineering.

Osphronemus goramy scales-derived type 1 Collagen induces RUNX2 and Osteocalcin expression: An in vivo Study

Introduction: Alveolar bone defects need bone augmentation therapies by subtituting with bone material. Gourami (Osphronemus goramy) fish scale comprises type 1 collagen and it has been used as scaffolding material in bone tissue engineering. As alternative bone graft material, the scales have a big potency to promote osteogenesis in periodontal bone defect when autografts are not feasible. This study will analise Runx2 and Osteocalcin expression in wistar rat alveolar bone induced by type 1 collagen derived from gourami fish scale. Methods: 32 male Wistar rats were divided into four groups; control group—7 days (C7), treatment group—7 days (P7), control group—14 days (C14), and treatment group—14 days (P14). The left mandibular incisivus was extracted and the tooth socket was treated with 10mg collagen. The rats were euthanized (at day 7th and 14th) and immunohistochemistry was performed using monoclonal antibodies anti-RUNX2 and anti-osteocalcin. Results: After seven days and 14days, the expression of RUNX2 and osteocalcin in the treatment group increased significantly (p<0.05) compared with the control group. Conclusion: Type 1 collagen from gourami (Osphronemus goramy) fish scales increases RUNX2 and osteocalcin expression as a bone growth marker.

Synthesis of pure and Cd-doped hydroxyapatite for the photo-catalytic degradation of Amoxicillin and Ciprofloxacin: Crystallographic characterization using XRD

Nanosized hydroxyapatite (HAp) is considered an elementary material for artificial bone tissue engineering and the applications are expanding and one of them is the photocatalytic degradation of environmentally hazardous pollutants. In this research, HAp nanoparticles, in pure form and doped with cadmium (Cd), were synthesized using a conventional wet-chemical precipitation method. Additionally, the synthesized samples such as pure and Cd-doped HAp were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and UV–Vis spectroscopy. Moreover, the XRD analysis allowed for a detailed estimation of the crystallite size, assisting in their tailoring of increased photocatalytic activity. The crystallite sizes of the nano-crystallite Hap were evaluated using the Scherrer Method (SM), Williamson-Hall Method (WHM), Size-Strain Plot (SSP), Halder-Wagner Method (HWM), and Sahadat-Scherrer Method (SSM). The models confirmed the formation of nano crystallite hydroxyapatite in pure and doped form. Cadmium doping in HAp showed great photocatalytic activity for example at 150 min, 31 % amoxicillin and 52 % ciprofloxacin were degraded upon 1.5 wt % Cd doping in HAp crystal. The research demonstrated that doping Cd in HAp crystal improved photocatalytic activity towards antibiotic solution (ciprofloxacin and amoxicillin) under all test circumstances.

Rapid fabrication of biomimetic PLGA microsphere incorporated with natural porcine dermal aECM for bone regeneration.

Bioactive microspheres coated with acellular extracellular matrix (aECM) have received extensive attention in bone tissue engineering. In this work, biomimetic microspheres with different aECM ratios, uniform size and controllable size were prepared easily by blending natural porcine dermal aECM and poly (lactic-co-glycolic acid) (PLGA) using electrohydrodynamic spraying and solidification actuated by solvent extraction method. In this work, the appropriate polymer concentration and preparation voltage were investigated, and the surface morphology of the microspheres was observed by scanning electron microscope. Sirius red was used to visualize aECM exposure on the surface of the microspheres. The in vitro and in vivo experiments were carried out to evaluate the bioactivity and osteogenic properties of the microspheres. The results showed that the morphology and size of PLGA microspheres had little influence on the aECM blending. In vitro experiments showed that the higher the content of aECM, the better the cell adhesion performance. In vivo, rat calvarial defect models were observed and characterized at 4 and 8 weeks postoperatively, and the values of BV/TV of 50aECM/PLGA were 47.57 ± 1.14% and 72.92 ± 2.19%, respectively. The results showed that the skull healing effect was better in aECM-containing microspheres. In conclusion, aECM/PLGA composite microspheres can increase cell adhesion performance through the addition of aECM. Moreover, in vivo experiments have proved that aECM/PLGA microspheres are beneficial to bone repair, which means the aECM/PLGA microspheres are a promising bone tissue engineering material.

Immunoregulation in Skull Defect Repair with a Smart Hydrogel Loaded with Mesoporous Bioactive Glasses.

Skull defect repair is a complex and critical medical challenge, and there is an urgent need to develop multifunctional tissue engineering scaffolds for skull regeneration. The success of bone tissue engineering depends on the construction of scaffolds that can regulate the immune microenvironment of bone regeneration and mimic the liquid crystal and viscoelastic properties of natural bone extracellular matrix. Hence, a smart hydrogel (PEGDA5/AM15/CLC-BMP-4@MBG) with good biocompatibility and the ability to modulate the wound immune microenvironment has been developed for the repair of skull defects. The hydrogel consists of chitin liquid crystal hydrogel (PEGDA5/AM15/CLC) and mesoporous bioactive glasses (MBGs) loaded with bone morphogenetic protein-4 (BMP-4). The liquid crystal hydrogel not only offers the necessary biological support and mechanical properties but also maintains the stability of the liquid crystal state, facilitating adhesion and regeneration of surrounding bone tissue. In addition, BMP-4@MBG intelligently regulates the release rate of BMP-4 in response to changes in wound microenvironment, thus effectively promoting the transformation of macrophages from M1 to M2 macrophages. At the same time, Ca2+ and Si4+ released by MBG degradation and BMP-4 synergically promote bone repair process. The PEGDA5/AM15/CLC-BMP-4@MBG hydrogel shows excellent immunomodulatory and osteogenic properties of bone microenvironment and is a promising scaffold material for bone tissue engineering.

Carboxymethyl cellulose-stabilized calcium phosphate particles for injectable hydrogel-based bone tissue engineering.

Calcium phosphate (CaP) is a widely used biocompatible and bioactive material for bone tissue engineering due to its similarity to the mineral component of natural bone. Amorphous calcium phosphate is a highly reactive form of CaP that can undergo a phase transformation into a more stable crystalline phase, making it an attractive candidate for bone regeneration applications. However, amorphous CaP is highly unstable in aqueous solutions, which limits its use in practical applications. To overcome this limitation, this research aimed to employ carboxymethyl cellulose (CMC), a water-soluble biopolymer, as a stabilizer for CaP particles. CMC can form a protective layer around CaP particles, enhancing their stability and dispersion in aqueous solutions. An in situ wet chemical process was used to prepare CaP/CMC particles. A concentration of 500 mg L-1 of CMC was found to effectively stabilize the synthesized CaP particles, resulting in good dispersity. These particles were then integrated into an injectable hydrogel made of methacrylated hyaluronic acid (MeHA) to create a promising material for bone regeneration applications. The use of CaP and CMC in combination with an injectable MeHA hydrogel provides a promising approach to develop a stable, injectable material for bone regeneration.

Effects of aligned PLGA/SrCSH composite scaffolds on in vitro growth and osteogenic differentiation of human mesenchymal stem cells.

Strontium (Sr) has important functions in bone remodeling. Incorporating strontium-doped α-calcium sulfate hemihydrate (SrCSH) into poly(lactic-co-glycolic acid) (PLGA) fibrous scaffolds were expected to increase its bio-activity and provide a potential material for bone tissue engineering. In the present study, Sr-containing aligned PLGA/SrCSH fibrous scaffolds similar to the architecture of natural bone were prepared via wet spinning. CCK-8 assay revealed that Sr-containing scaffolds possessed better bioactivity and supported favorable cell growth effectively. The aligned PLGA/SrCSH fibers exerted a contact effect on cell attachment, inducing regular cell alignment and influencing a series of cell behaviors. Releasing of high concentration Sr from a-PLGA/SrCSH scaffolds could induce high expression levels of BMP-2, increase ALP activity and upregulate RUNX-2 expression, and further promote the expressions of COL-I and OCN and the maximum mineralization. This study demonstrated that Sr and ordered structure in a-PLGA/SrCSH fibrous scaffolds could synergistically enhance the osteogenic differentiation of umbilical cord mesenchymal stem cells (UCMSCs) by regulating cell arrangement and expressions of osteogenic genes.

Imprinting Bone Surface Topography on Cast Metal

Chemical and physical features including stiffness and roughness texture of the biomaterials are important factors for in-vitro and in-vivo cell behaviour. Bone mimetic topography of the biomaterials can enhance the cell adhesion, cell proliferation and differentiation, leading to promoted bone tissue regeneration. In this study, a new technique for transferring the topography of the decellularized cortical bone to the cast metal was described. Imprinting efficiency and accuracy were high, as shown with light microscopy and atomic force microscopy. This method will pave the way for the development of new materials for bone tissue engineering.

Magnesium-Doped Nano-Hydroxyapatite/Polyvinyl Alcohol/Chitosan Composite Hydrogel: Preparation and Characterization.

Polyvinyl alcohol/Chitosan hydrogel is often employed as a carrier because it is non-toxic, biodegradable, and has a three-dimensional network structure. Meanwhile, Magnesium-doped nano-hydroxyapatite(Mg-nHA) demonstrated high characterization to promote the osteogenic differentiation of bone marrow derived mesenchymal stem cell(BMSCs). Therefore, in order to develop a porous hydrogel scaffold for the application of bone tissue engineering, an appropriate-type Mg-nHA hydrogel scaffold was developed and evaluated. A composite hydrogel containing magnesium-doped nano-hydroxyapatite (Mg-nHA/PVA/CS) was developed using a magnetic stirring-ion exchange method and cyclic freeze-thaw method design, with polyvinyl alcohol and chitosan as the main components. Fourier transform infrared spectra (FTIR), electron energy dispersive spectroscopy (EDS), X-ray photoelectron spectrometer (XPS) and scanning electron microscopy (SEM) were employed to analyze the chemical structure, porosity, and elemental composition of each hydrogels. The equilibrium swelling degree, moisture content, pH change, potential for biomineralization, biocompatibility, the osteogenic potential and magnesium ion release rate of the composite hydrogel were also evaluated. SEM analysis revealed a well-defined 3D spatial structure of micropores in the synthesised hydrogel. FTIR analysis showed that doping nanoparticles had little effect on the hydrogel's structure and both the 5% Mg-nHA/PVA/CS and 10% Mg-nHA/PVA/CS groups promoted amide bond formation. EDS observation indicated that the new material exhibited favourable biomineralization ability, with optimal performance seen in the 5% Mg-nHA/PVA/CS group. The composite hydrogel not only displayed favourable water content, enhanced biocompatibility, and porosity (similar to human cancellous bone), but also maintained an equilibrium swelling degree and released magnesium ions that created an alkaline environment around it. Additionally, it facilitated the proliferation of bone marrow mesenchymal stem cells and their osteogenic differentiation. The Mg-nHA/PVA/CS hydrogel demonstrates significant potential for application in the field of bone repair, making it an excellent composite material for bone tissue engineering.

Enhanced bone regeneration by osteoinductive and angiogenic zein/whitlockite composite scaffolds loaded with levofloxacin.

Promoting angiogenesis following biomaterial implantation is essential to bone tissue regeneration. Herein, the composite scaffolds composed of zein, whitlockite (WH), and levofloxacin (LEVO) were fabricated to augment bone repair by facilitating osteogenesis and angiogenesis. First, three-dimensional composite scaffolds containing zein and WH were prepared using the salt-leaching method. Then, as a model antibiotic drug, the LEVO was loaded into zein/WH scaffolds. Moreover, the addition of WH enhanced the adhesion, differentiation, and mineralization of osteoblasts. The zein/WH/LEVO composite scaffolds not only had significant osteoinductivity but also showed excellent antibacterial properties. The prepared composite scaffolds were then implanted into a calvarial defect model to evaluate their osteogenic induction effects in vivo. Micro-CT observation and histological analysis indicate that the scaffolds can accelerate bone regeneration with the contribution of endogenous cytokines. Based on amounts of data in vitro and in vivo, the scaffolds present profound effects on improving bone regeneration, especially for the favorable osteogenic, intensive angiogenic, and alleviated inflammation abilities. The results showed that the synthesized scaffolds could be a potential material for bone tissue engineering.

Research progress of biomedical polymer materials in bone tissue engineering

Defects, defects and dysfunctions caused by disease, surgery or aging are among the most important threats to human health. Although organ transplantation and surgical reconstruction rehabilitation treatment measures have saved or prolonged a small number of lives, they still have shortcomings and limitations. Biomedical polymer materials have great potential in bone tissue engineering, and with the progress of material science, molecular biology, medicine and other fields, their application in bone tissue engineering is becoming more and more extensive. This paper introduces the types and polymer properties of biomedical polymer materials in bone tissue engineering, and introduces and prospects the current development of biomedical polymer materials in the field of bone tissue engineering.

Advances in the Application of Photothermal Composite Scaffolds for Osteosarcoma Ablation and Bone Regeneration.

Photothermal therapy is a promising approach to cancer treatment. The energy generated by the photothermal effect can effectively inhibit the growth of cancer cells without harming normal tissues, while the right amount of heat can also promote cell proliferation and accelerate tissue regeneration. Various nanomaterials have recently been used as photothermal agents (PTAs). The photothermal composite scaffolds can be obtained by introducing PTAs into bone tissue engineering (BTE) scaffolds, which produces a photothermal effect that can be used to ablate bone cancer with subsequent further use of the scaffold as a support to repair the bone defects created by ablation of osteosarcoma. Osteosarcoma is the most common among primary bone malignancies. However, a review of the efficacy of different types of photothermal composite scaffolds in osteosarcoma is lacking. This article first introduces the common PTAs, BTE materials, and preparation methods and then systematically summarizes the development of photothermal composite scaffolds. It would provide a useful reference for the combination of tumor therapy and tissue engineering in bone tumor-related diseases and complex diseases. It will also be valuable for advancing the clinical applications of photothermal composite scaffolds.

Effect of Different Contents of 63s Bioglass on the Performance of Bioglass-PCL Composite Bone Scaffolds

Bioactive glasses (BG), notably 63s BG, possess distinct properties such as biodegradability, biocompatibility, and the ability to boost cellular interactions. Our research concentrated on formulating polycaprolactone (PCL) porous scaffolds enriched with 63s BG to gauge their combined mechanical and biological potentials. Using twin-screw extrusion, we created composites containing 5%, 10%, and 20% 63s BG. These were transformed into cylindrical scaffolds using 3D printing. Our assessments involved melt flow, SEM, XRD, water contact angle metrics, DSC, and extracorporeal degradation. After co-culturing with MC3T3-E1 cells, an uptick in alkaline phosphatase activity was noted. Preliminary findings demonstrated that as 63s BG content increased, the properties of the composites improved. Yet, they fell short of replicating the mechanical nuances of cortical bone, rendering them inapt for load-bearing orthopedic applications but suitable for mending minor bone defects or cartilage. In summary, while 63s BG brings about significant advancements in scaffold attributes, attaining the mechanical traits ideal for certain medical purposes remains elusive. This investigation offers foundational insights for the evolution of optimized bone tissue engineering materials.

Application of gelatin microspheres in bone tissue engineering

Gelatin microspheres were discussed as a scaffold material for bone tissue engineering, with the advantages of its porosity, biodegradability, biocompatibility, and biosafety highlighted. This review discusses how bone regeneration is aided by the three fundamental components of bone tissue engineering-seed cells, bioactive substances, and scaffold materials-and how gelatin microspheres can be employed for in vitro seed cell cultivation to ensure efficient expansion. This review also points out that gelatin microspheres are advantageous as drug delivery systems because of their multifunctional nature, which slows drug release and improves overall effectiveness. Although gelatin microspheres are useful for bone tissue creation, the scaffolds that take into account their porous structure and mechanical characteristics might be difficult to be created. This review then discusses typical techniques for creating gelatin microspheres, their recent application in bone tissue engineering, as well as possible future research directions.