Scaffolds For Bone Tissue Engineering Research Articles

Application of smart hydrogels scaffolds for bone tissue engineering

Application of smart hydrogels scaffolds for bone tissue engineering

3D Printing of Polyester Scaffolds for Bone Tissue Engineering: Advancements and Challenges

AbstractPolyesters have garnered significant attention in bone tissue engineering (BTE) due to their tunable degradation rates, biocompatibility, and convenient processing. This review focuses on recent advancements and challenges in the 3D printing of polyester‐based scaffolds for BTE. Various 3D printing techniques, such as fused deposition modeling (FDM), selective laser sintering (SLS), vat photopolymerization (VP), and Wet‐spun additive manufacturing, are explored, emphasizing their ability to construct scaffolds with precise architectural control. The main challenges in 3D printed polyester scaffolds are their limited mechanical properties, lack of inherent bioactivity, and the release of acidic byproducts during biodegradation. Strategies to enhance scaffold performance, such as incorporating bioactive ceramics and growth factors, are discussed, focusing on improving osteoconductivity, osteoinductivity, and mechanical strength. Recent studies on integrating these components into polyester scaffolds and techniques to optimize scaffold porosity and biodegradability are presented. Finally, the review addresses ongoing issues, such as the difficulty of incorporating some biomolecules and bioceramics during 3D printing and improved clinical translation. This comprehensive overview aims to provide insight into the future directions and potential solutions for overcoming the limitations of 3D‐printed polyester‐based scaffolds in BTE.

Advances and Challenges in Polymer-Based Scaffolds for Bone Tissue Engineering: A Path Towards Personalized Regenerative Medicine

Polymers have become essential in advancing bone tissue engineering, providing adaptable bone healing and regeneration solutions. Their biocompatibility and biodegradability make them ideal candidates for creating scaffolds that mimic the body’s natural extracellular matrix (ECM). However, significant challenges remain, including degradation by-products, insufficient mechanical strength, and suboptimal cellular interactions. This article addresses these challenges by evaluating the performance of polymers like poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), and polylactic acid (PLA) in scaffold development. It also explores recent innovations, such as intelligent polymers, bioprinting, and the integration of bioactive molecules to enhance scaffold efficacy. We propose that overcoming current limitations requires a combination of novel biomaterials, advanced fabrication techniques, and tailored regulatory strategies. The future potential of polymer-based scaffolds in personalised regenerative medicine is discussed, focusing on their clinical applicability.

Biomimetic Mineralized Collagen Scaffolds for Bone Tissue Engineering: Strategies on Elaborate Fabrication for Bioactivity Improvement.

Biomimetic mineralized collagen (BMC) scaffolds represent an innovative class of bone-repair biomaterials inspired by the natural biomineralization process in bone tissue. Owing to their favorable biocompatibility and mechanical properties, BMC scaffolds have garnered significant attention in bone tissue engineering. However, most studies have overlooked the importance of bioactivity, resulting in collagen scaffolds with suboptimal osteogenic potential. In this review, the composition of the mineralized extracellular matrix (ECM) in bone tissue is discussed to provide guidance for biomimetic collagen mineralization. Subsequently, according to the detailed fabrication procedure of BMC scaffolds, the substances that can regulate both the fabrication process and biological activities is summarized. Furthermore, a potential strategy for developing BMC scaffolds with superior mechanical properties and biological activities for bone tissue engineering is proposed.

Cytoskeletal regulation on polycaprolactone/graphene porous scaffolds for bone tissue engineering

Understanding cellular mechanics requires evaluating the mechanical and chemical cues that regulate the actin cytoskeleton, particularly filopodia and lamellipodia. Therefore, this study aims to investigate the effect of scaffolds properties on cell migration. The results showed that scaffolds toughness, strain, and strength played a key role in promoting cell movement by stimulating the dynamic formation of filopodia and lamellipodia. The test sample containing 3 wt% G significantly enhanced toughness, yield strength, and strain, leading to increase cell motility as well as enhanced development of longer filopodia and larger lamellipodia in MG-63 cells. These results provide valuable insights for optimizing scaffolds to promote bone tissue regeneration.

Impact of Particle Size and Sintering Temperature on Calcium Phosphate Gyroid Structure Scaffolds for Bone Tissue Engineering

Impact of Particle Size and Sintering Temperature on Calcium Phosphate Gyroid Structure Scaffolds for Bone Tissue Engineering

Role of crosslinkers in advancing chitosan-based biocomposite scaffolds for bone tissue engineering: A comprehensive review

Bone tissue engineering (BTE) aims to repair and regenerate damaged bone tissue by combining cells, scaffolds, and signaling molecules. Various macromolecules, including natural polymers like chitosan (CS), collagen, hyaluronic acid, and alginate, as well as synthetic polymers such as polyethylene glycol and polylactic acid, are used in scaffold fabrication. Among these, CS holds significant potential in BTE due to its biocompatibility, biodegradability, and other features. The inherent mechanical weaknesses of CS-based scaffolds require the implementation of crosslinking strategies to improve their stability and overall performance. Physical crosslinkers like ultra-violet irradiation and freeze-thaw cycles are biocompatible but offer limited mechanical strength. Chemical crosslinkers like glutaraldehyde significantly improve mechanical strength, but they may induce cytotoxicity. We briefly outline here the critical role of physical and chemical crosslinkers in improving the physicochemical properties, mechanical strength, biocompatibility, and biological functions of CS-based scaffolds, including effective bone regeneration. The influence of crosslinking on the CS-based scaffolds' bioactivity, including the controlled release of bioactive molecules, is also discussed. A thorough understanding of crosslinker chemistry and application in CS-based scaffolds is essential for advancing bone regeneration therapies.

A Review on Advances and Challenges in Core-Shell Scaffolds for Bone Tissue Engineering: Design, Fabrication, and Clinical Translation.

This review explores core-shell scaffolds in bone tissue engineering, highlighting their osteoconductive and osteoinductive properties critical for bone growth and regeneration. Key design factors include material selection, porosity, mechanical strength, biodegradation kinetics, and bioactivity. Electrospun core-shell nanofibrous scaffolds demonstrate potential in delivering therapeutic agents and enhancing bone regeneration. Critical characterization techniques include structural, surface, chemical composition, mechanical, and degradation analyses. Scaling up production poses challenges, addressed by innovative electrospinning techniques. Future research focuses on regulatory and commercial considerations, while exploring advanced materials and fabrication methods to optimize scaffold performance for improved clinical outcomes.

The induction of bone formation by 3D-printed PLGA microsphere scaffolds in a calvarial orthotopic mouse model: a pilot study.

Polymeric biodegradable microspheres are readily utilized to support targeted drug delivery for various diseases clinically. 3D printed tissue engineering scaffolds from polymer filaments with embedded microspheres or nanoparticles, as well as bulk microsphere scaffolds, have been investigated for regenerative medicine and tissue engineering. However, 3D printed scaffolds consisting only of a homogenous microsphere size with an optimized architecture that includes a unique micro- and macroporosity, have been challenging to produce and hence, have not been assessed in the literature yet. Utilizing our recently established 3D-MultiCompositional Microsphere-Adaptive Printing (3D-McMap) method, the present study evaluated the effectiveness of 3D-printed poly (lactic-co-glycolic acid) (PLGA) microsphere scaffolds, consisting of microsphere sizes 50, 100, or 200μm, on the induction of bone formation when implanted in the calvarial murine regeneration model. Our results showed that PLGA microsphere scaffolds possess unique properties that support bone regeneration by supporting osteoconduction and stimulating, in our opinion, true spontaneous osteoinduction. The study demonstrated that PLGA microsphere-based scaffolds support bone growth in the absence of additional growth factors and promote osteogenesis primarily via their unique geometric configuration. The larger the microspheres were, the greater de novo bone formation was. This proves that bone tissue engineering scaffolds 3D printed from microspheres, enabled by the 3D-McMap method, are superior over bulk material printed scaffolds, as they possess the unique capability of spontaneous induction of new bone formation. With the addition of encapsulated modulatory bone-forming biomolecules they can substantially improve the spatiotemporal control of tissue morphogenesis, potentially leading to new innovative clinical tissue repair therapies that regenerate bone in large defects correctly and fully.

Mathematical modeling of bioactive glass degradation

Bioactive glasses (BGs) are promising for bone tissue engineering (BTE). Mathematical modeling is a powerful tool for understanding BTE scaffold degradation. We developed mathematical functions based on chemical reaction equations governing dissolution and diffusion processes to model the degradation of 45S5 BGs. An empirical mathematical model was employed to characterize the formation process of hydroxycarbonate apatite (HCA). Two sets of numerical simulations with BG powder and bulk samples immersed in simulated body fluid were compared with in vitro experiments to validate and parameterize the model. The model could accurately predict BG degradation and HCA formation. Our findings indicate that the proposed parameters K1=2600 mm/(μmol·h), K2=2.0 mm/h and K3=0.001 mm/h are suitable for simulating the degradation of silicate-based BGs, specifically 45S5 BG. The proposed model successfully predicted the degradation behavior and subsequent HCA formation over 21 days. The proposed mathematical model serves as a valuable tool for designing degradable BG-containing scaffolds.

Plant-based scaffolds and osteogenesis: A systematic review.

To enhance the understanding and usefulness of decellularised plant tissues as scaffolds for bone tissue engineering, and to review the recent advances in plant-based scaffolds for bone regeneration. The systematic review was conducted from February to June 2022, and comprised literature search on PubMed and Science Direct databases for articles published in the English language between 2013 and June, 2022. The search was conducted using key words 'plant-based scaffolds and osteogenesis' and 'decellularised plant and scaffolds and bone tissue engineering' and 'plant root-based scaffold and bone formation'. Full-text articles and short communication covering both in vitro and in vivo studies focussing on plant-based scaffolds for osteogenesis were included. Additional references that satisfied the inclusion criteria were found on Google Scholar and included in the review. Quality evaluation of the studies included was done independently by two researchers, and the risk of bias was calculated and categorised as low, medium and high risk. Of the 564 articles, 10(1.77 %) were included; 6(60%) purely in vitro studies, and 4(40%) studies having both in vitro and in vivo components. Decellularized plant tissue alone was used as three-dimensional scaffold materials in 5(50%) studies, but in 4(40%) studies, plant-based composite scaffolds were used. The risk of bias was medium in 7(70%) studies. Plant-based scaffolds promote osteogenesis, but more in vivo research on plant-based studies is needed to label it as suitable scaffolds for bone tissue engineering.

Applications of hydroxyapatite-based polymeric scaffolds in bone tissue engineering: An update

Bone tissue is a comprising of an organic and inorganic environment, in which the collagen element and the mineral part are structured into complex and spongy constructions. Hydroxyapatite (HAp) is the chief inorganic constituent of human bone. HAp is extensively utilized in bone tissue regeneration for its bioactivity and biocompatibility, and a rising number of investigators are discovering ways to recover the physical belongings and biological roles of HAp. However, this biomimetic material has poor mechanical properties, such as low tensile and compressive strength, which make it not suitable for bone tissue engineering (BTE). For this reason, HA is frequently utilized in a mixture with diverse polymers to increase their mechanical strengths and the general performance of the implantable biomaterials advanced for orthopedic usage. In this review, we attempt to contribute a brief and inclusive outline of HAp-based natural and synthetic polymer materials as reinforcing components and their applications in bone tissue engineering.

Dual-Function Femtosecond Laser: β-TCP Structuring and AgNP Synthesis via Photoreduction with Azorean Green Tea for Enhanced Osteointegration and Antibacterial Properties.

β-Tricalcium phosphate (β-TCP) is a well-established biomaterial for bone regeneration, highly regarded for its biocompatibility and osteoconductivity. However, its clinical efficacy is often compromised by susceptibility to bacterial infections. In this study, we address this limitation by integrating femtosecond (fs)-laser processing with the concurrent synthesis of silver nanoparticles (AgNPs) mediated by Azorean green tea leaf extract (GTLE), which is known for its rich antioxidant and anti-inflammatory properties. The fs laser was employed to modify the surface of β-TCP scaffolds by varying scanning velocities, fluences, and patterns. The resulting patterns, formed at lower scanning velocities, display organized nanostructures, along with enhanced roughness and wettability, as characterized by Scanning Electron Microscopy (SEM), optical profilometry, and contact angle measurements. Concurrently, the femtosecond laser facilitated the photoreduction of silver ions in the presence of GTLE, enabling the efficient synthesis of small, spherical AgNPs, as confirmed by UV-vis spectroscopy, Transmission Electron Microscopy (TEM), and Fourier Transform Infrared Spectroscopy (FTIR). The resulting AgNP-embedded β-TCP scaffolds exhibited a significantly improved cell viability and elongation of human bone marrow mesenchymal stem cells (hBM-MSCs), alongside significant antibacterial activity against Staphylococcus aureus (S. aureus). This study underscores the transformative potential of combining femtosecond laser surface modification with GTLE-mediated AgNP synthesis, presenting a novel and effective strategy for enhancing the performance of β-TCP scaffolds in bone-tissue engineering.

Carboxymethyl chitosan-enhanced multi-level microstructured composite hydrogel scaffolds for bone defect repair

Critical-sized bone defects (CSBDs) necessitate interventions like bone grafts or tissue engineering scaffolds to surpass the body's limited spontaneous healing capacity and ensure effective bone regeneration. A multi-level microstructured composite hydrogel 3D scaffold was fabricated for enhanced bone defect repair, integrating a 3D-printed macroporous polylactic acid (PLA) scaffold with polydopamine treatment and filled with a sodium alginate/nano hydroxyapatite/carboxymethyl chitosan (SA/nHA/CMCS) micrometer-scale porous composite hydrogel. The incorporation of nano hydroxyapatite (nHA) nanoparticles enhanced hydrogel crosslinking and osteogenic activity. A systematic evaluation of CMCS concentration demonstrated its pivotal role in enhancing hydrogel cross-linking and mineralization, regulating degradation rate adapted to the osteogenic cycle, endowing the scaffold with a bioactive micrometer-scale porous structure. In vitro studies confirmed the osteogenic effectiveness of the composite hydrogel 3D scaffold, particularly those with CMCS, which boosted bone mesenchymal stem cells (BMSCs) adhesion, proliferation, and differentiation. The rabbit tibial bone defect model further confirmed that, compared to the DAPLA (dopamine modified PLA) scaffold, the bone trabecular number of the DSHC (DAPLA-SA/nHA/CMCS) scaffold increases 2.06-fold. In conclusion, this study expanded the application of hydrogel scaffolds in bone tissue engineering and provided an effective strategy for the development of hydrogel implant materials.

Direct MultiSearch optimization of TPMS scaffolds for bone tissue engineering

BackgroundScaffolds designed for tissue engineering must consider multiple parameters, namely the permeability of the design and the wall shear stress experienced by the cells on the scaffold surface. However, these parameters are not independent from each other, with changes that improve wall shear stress, negatively impacting permeability and vice versa. This study introduces a novel multi-objective optimization framework using Direct MultiSearch (DMS) to design triply periodic minimal surface (TPMS) scaffolds for bone tissue engineering. MethodThe optimization algorithm focused on maximizing the permeability of the scaffolds and obtaining a desired value of average wall shear stress (which ranges between the values that promote osteogenic differentiation of 0.1 mPa and 10 mPa). Multiple fluid inlet velocities and target wall shear stress were analyzed. The DMS method successfully generated Pareto fronts for each configuration, enabling the selection of optimized scaffolds based on specific structural requirements. ResultsThe findings reveal that increasing the target wall shear stress results in a greater number of non-dominated points on the Pareto front, highlighting a more robust optimization process. Additionally, it was also demonstrated that the tested Schwartz diamond scaffolds had a better permeability-wall shear stress relation when compared to Schoen gyroid geometries. ConclusionsDirect MultiSearch was proven as an effective tool to aid in the design of tissue engineering scaffolds. This adaptable optimization framework has potential applications beyond bone tissue engineering, including cartilage tissue differentiation.

Determination of the Optimum Architecture of Additively Manufactured Magnetic Bioactive Glass Scaffolds for Bone Tissue Engineering and Drug-Delivery Applications.

For better bone regeneration, precise control over the architecture of the scaffolds is necessary. Because the shape of the pore may affect the bone regeneration, therefore, additive manufacturing has been used in this study to fabricate magnetic bioactive glass (MBG) scaffolds with three different architectures, namely, grid, gyroid, and Schwarz D surface with 15 × 15 × 15 mm3 dimensions and 70% porosity. These scaffolds have been fabricated using an in-house-developed material-extrusion-based additive manufacturing system. The composition of bioactive glass was selected as 45% SiO2, 20% Na2O, 23% CaO, 6% P2O5, 2.5% B2O3, 1% ZnO, 2% MgO, and 0.5% CaF2 (wt %), and additionally 0.4 wt % of iron carbide nanoparticles were incorporated. Afterward, MBG powder was mixed with a 25% (w/v) Pluronic F-127 solution to prepare a slurry for fabricating scaffolds at 23% relative humidity. The morphological characterization using microcomputed tomography revealed the appropriate pore size distribution and interconnectivity of the scaffolds. The compressive strengths of the fabricated grid, gyroid, and Schwarz D scaffolds were found to be 14.01 ± 1.01, 10.78 ± 1.5, and 12.57 ± 1.2 MPa, respectively. The in vitro study was done by immersing the MBG scaffolds in simulated body fluid for 1, 3, 7, and 14 days. Darcy's law, which describes the flow through porous media, was used to evaluate the permeability of the scaffolds. Furthermore, an anticancer drug (Mitomycin C) was loaded onto these scaffolds, wherein these scaffolds depicted good release behavior. Overall, gyroid-structured scaffolds were found to be the most suitable among the three scaffolds considered in this study for bone tissue engineering and drug-delivery applications.

Design, fabrication and biocompatibility of 3D printed poly (LLA-ran-PDO-ran-GA)/poly(D-lactide) composite scaffolds for bone tissue engineering

Design, fabrication and biocompatibility of 3D printed poly (LLA-ran-PDO-ran-GA)/poly(D-lactide) composite scaffolds for bone tissue engineering

Hierarchical materials with interconnected pores from capillary suspensions for bone tissue engineering

AbstractThe increasing demand for bone grafts due to the aging population has opened new opportunities for the manufacture of porous ceramics to assist in bone reconstruction. In our study, we investigate a new, promising method to manufacture hierarchically porous structures in a straightforward and tunable way. It consists of combining the novel technology of capillary suspensions, formed by mixing solid particles and two immiscible liquids, one less than 5 vol%, with freeze casting. We have successfully achieved alumina and beta‐tricalcium phosphate (β‐TCP) materials with both <2 µm and 20–50 µm as the smallest and largest pore sizes, respectively. The microstructure exhibits fully open pores and high levels of porosity (>60%). The capillary suspensions’ rheological behavior indicates that silica nano‐suspensions as a secondary fluid creates a stronger internal particle network than sucrose for the alumina system. Conversely, the opposite was observed with the β‐TCP system. These differences were attributed to the change in affinity between the secondary fluids and the solid loading. In our study, both systems have served to deepen the knowledge about the new area of capillary suspensions and proved their use in hierarchical porous scaffolds for bone tissue engineering.

Fabrication and characterization of nanohydroxyapatite/chitosan/decellularized placenta scaffold for bone tissue engineering applications

Novel biomaterials are necessary to fabricate biomimetic scaffolds for bone tissue engineering. In the present experiment, we aimed to fabricate and evaluate the osteogenic properties of nanohydroxyapatite/chitosan/decellularized placenta (nHA.Cs.dPL) composite scaffolds. The human placenta was decellularized (dPL), characterized, and digested in pepsin to form the hydrogel. nHA.Cs.dPL scaffolds were fabricated using salt leaching/freeze drying and evaluated for their morphology, chemical composition, swelling, porosity, degradation, mechanical strength, and biocompatibility. Saos-2 cells were seeded on scaffolds, and their osteogenic properties were investigated by evaluating alkaline phosphatase (ALP), osteocalcin (OCN), collagen type 1 (COL I) expression, and calcium deposition under osteogenic differentiation. The dPL was prepared with minimized DNA content and a well-preserved porous structure. Scaffolds were highly porous with interconnected pores and exhibited appropriate swelling and degradation rates supporting saos-2 cell attachment and proliferation. dPL improved scaffold physicochemical features and increased cell proliferation, ALP, OCN, COL I expression, and calcium deposition under osteogenic differentiation induction. nHA.Cs.dPL composite scaffolds provide a 3D microenvironment with superior physicochemical features that support saos-2 cell adhesion, proliferation, and osteogenic differentiation.

Leveraging Machine Learning for Optimized Mechanical Properties and 3D Printing of PLA/cHAP for Bone Implant.

This study explores the fabrication and characterisation of 3D-printed polylactic acid (PLA) scaffolds reinforced with calcium hydroxyapatite (cHAP) for bone tissue engineering applications. By varying the cHAP content, we aimed to enhance PLA scaffolds' mechanical and thermal properties, making them suitable for load-bearing biomedical applications. The results indicate that increasing cHAP content improves the tensile and compressive strength of the scaffolds, although it also increases brittleness. Notably, incorporating cHAP at 7.5% and 10% significantly enhances thermal stability and mechanical performance, with properties comparable to or exceeding those of human cancellous bone. Furthermore, this study integrates machine learning techniques to predict the mechanical properties of these composites, employing algorithms such as XGBoost and AdaBoost. The models demonstrated high predictive accuracy, with R2 scores of 0.9173 and 0.8772 for compressive and tensile strength, respectively. These findings highlight the potential of using data-driven approaches to optimise material properties autonomously, offering significant implications for developing custom-tailored scaffolds in bone tissue engineering and regenerative medicine. The study underscores the promise of PLA/cHAP composites as viable candidates for advanced biomedical applications, particularly in creating patient-specific implants with improved mechanical and thermal characteristics.