Scaffolds For Bone Tissue Engineering Research Articles

3D printing of personalized magnesium composite bone tissue engineering scaffold for bone and angiogenesis regeneration

Critical-size trabecular bone defects remain challenging to treat in orthopedic clinical practice. This study utilized a polyethylene glycol dispersion method to uniformly disperse magnesium (Mg) and nano-hydroxyapatite (n-HA) in a polylactic acid (PLA) solution, resulting in the fabrication of an Mg/n-HA/PLA composite material. We next generated personalized bone repair scaffolds through Fused Deposition Modeling (FDM) 3D printing. The composite scaffolds were characterized, and their biocompatibility, osteogenic properties, and angiogenic capabilities were assessed through in vitro experiments. In vivo experiments were conducted to explore the pathways underlying osteogenesis and angiogenesis. The results confirmed that the properties and biological efficacy of the Mg composite material could be regulated by controlling the quantitative ratio of Mg. The results showed that the 10 % Mg composite group exhibited optimal osteogenic properties, whereas the 20 % Mg composite group showed the best angiogenic effects and the most promising induction properties. The beneficial effect of the composite scaffold was associated with the interconnected REK and FAK/HIF-1/VEGF signaling pathways. In conclusion, the Mg composite biomaterial exhibited desirable processability, mechanical properties, and degradability, and induced osteogenesis and angiogenesis. These features of composite scaffold meet the complex requirements for treating critical-size trabecular bone defects in load-bearing animals and having potential for clinical development and application.

Integrated GelMA and interleukin 8-loaded liposome composite scaffold for endogenous BMSCs recruitment in bone repair

Bone repair strategies, based on endogenous stem cell recruitment, can effectively avoid immune rejection and the low utilization of exogenous stem cells. Endogenous stem cells can be recruited to the implantation site by loading chemokines onto bone tissue-engineered scaffolds. However, challenges such as unstable chemokine activity and easy inactivation after implantation remain significant. In the present study, composite fiber scaffolds ((IL8@LIP)-GelMA) consisting of Interleukin 8 (IL8) -loaded liposomes and GelMA were constructed by electrospinning and photocrosslinking, and its ability to recruit bone marrow-derived mesenchymal stem cells (BMSCs) and immunomodulatory effect was investigated. Compared to GelMA loaded directly with IL8, scaffolds of (IL8@LIP)-GelMA demonstrated superior protection of IL8 activity, ensuring a slow and continuous release. Both in vivo and in vitro experiments demonstrated that the (IL8@LIP)-GelMA scaffolds effectively recruited BMSCs to the desired sites. Additionally, the (IL8@LIP)-GelMA scaffolds exhibited the capacity to recruit more macrophages to the implantation site. Importantly, they promoted the polarization of macrophages toward the M2 anti-inflammatory phenotype, facilitating the transition from the inflammatory stage to the tissue repair stage. Therefore, (IL8@LIP)-GelMA scaffolds show great potential for cell-free tissue engineering applications and provide insights into the loading mode of growth factors in scaffolds.

Chitosan and Sodium Hyaluronate Hydrogels Supplemented with Bioglass for Bone Tissue Engineering.

The aim of the study was to produce biocomposites based on chitosan and sodium hyaluronate hydrogels supplemented with bioglasses obtained under different conditions (temperature, time) and to perform an in vitro evaluation of their cytocompatibility using both indirect and direct methods. Furthermore, the release of ions from the composites and the microstructure of the biocomposites before and after incubation in simulated body fluid were assessed. Tests on extracts from bioglasses and hydrogel biocomposites were performed on A549 epithelial cells, while MG63 osteoblast-like cells were tested in direct contact with the developed biomaterials. The immune response induced by the biomaterials was also evaluated. The experiments were carried out on both unstimulated and lipopolysaccharide (LPS) endotoxin-stimulated human peripheral blood cells in the presence of extracts of the biocomposites and their components. Extracts of the materials produced do not exhibit toxic effects on A549 cells, and do not increase the production of proinflammatory cytokines tumour necrosis factor alpha (TNF-α) and interleukin (IL-6) by blood cells in vitro. In direct contact with MG63 osteoblast-like cells, biocomposites containing the reference bioglass and those containing SrO are more cytocompatible than biocomposites with ZnO-doped bioglass. Using two testing approaches, the effects both of the potentially toxic agents released and of the surface of the tested materials on the cell condition were assessed. The results pave the way for the development of highly porous hydrogel-bioglass composite scaffolds for bone tissue engineering.

Baghdadite reinforced polycaprolactone scaffold for bone tissue engineering

Baghdadite reinforced polycaprolactone scaffold for bone tissue engineering

The effects of gellan gum concentration on electrospinning and degradation of flexible, crosslinker-free scaffolds for bone tissue engineering

Low acyl type gellan gum (GG) is a biocompatible gelling agent with lower degradation rates compared to its high acyl counterpart. This study investigated the hypothesis whether the incorporation of various low acyl GG concentrations into a constant concentration of poly(vinyl alcohol) (PVA) would facilitate the electrospinning towards the production of stable nanofibrous PVA-GG membranes, and how thermal treatment would affect the degradation rate of the membranes rendering them suitable as flexible scaffolds for bone tissue engineering and avoiding crosslinking agents. All compositions displayed fiber diameters ranging from 70 to 200 nm. Thermally treated membranes indicated a mass loss of 20–32 %, while non-treated ones 32–54 %, with the higher GG concentrations exhibiting lower degradation rates, and swelling capacity of at least 500 %. Rheological analysis illustrated differences in gelling capacity, ranging from fluid-like to critical gelation state with increasing GG content, with G′ values ranging between 3.5 ± 0.5 Pa for the lowest and 23.4 ± 1.5 for the highest GG concentration. Proliferation of strongly adhered pre-osteoblasts significantly increased over culture time. Osteogenic markers including alkaline phosphatase activity and calcium deposition were significantly upregulated compared to the control, and calcium secretion gradually increased up to three weeks, validating the capacity of the scaffolds to support osteogenesis.

Preparation of PDA-GO/CS composite scaffold and its effects on the biological properties of human dental pulp stem cells

Reduced graphene oxide (rGO) is an graphene oxide (GO) derivative of graphene, which has a large specific surface area and exhibited satisfactory physicochemical characteristics. In this experiment, GO was reduced by PDA to generate PDA-GO complex, and then PDA-GO was combined with Chitosan (CS) to synthesize PDA-GO/CS composite scaffold. PDA-GO was added to CS to improve the degradation rate of CS, and it was hoped that PDA-GO/CS composite scaffolds could be used in bone tissue engineering. Physicochemical and antimicrobial properties of the different composite scaffolds were examined to find the optimal mass fraction. Besides, we examined the scaffold’s biocompatibility by Phalloidin staining and Live and Dead fluorescent staining.Finally, we applied ALP staining, RT-qPCR, and Alizarin red S staining to detect the effect of PDA-GO/CS on the osteogenic differentiation of human dental pulp stem cells (hDPSCs). The results showed that PDA-GO composite was successfully prepared and PDA-GO/CS composite scaffold was synthesized by combining PDA-GO with CS. Among them, 0.3%PDA-GO/CS scaffolds improves the antibacterial activity and hydrophilicity of CS, while reducing the degradation rate. In vitro, PDA-GO/CS has superior biocompatibility and enhances the early proliferation, migration and osteogenic differentiation of hDPSCs. In conclusion, PDA-GO/CS is a new scaffold materialsuitable for cell culture and has promising application prospect as scaffold for bone tissue engineering.

Characterization of PVA/Chitosan and Tuna Fish Bones CHA Scaffold for Bone Tissue Engineering

Bone tissue engineering has been used in the biomedical field to treat bone defects by implanting scaffolds into bone tissue. However, the currently developed scaffold still needs to be developed to obtain scaffold building materials with good compatible properties and can regenerate damaged bone cells. This study combines PVA/Chitosan polymer with CHA of tuna bone using the porogen leaching method at a calcination temperature of 100°C for 12 hours. The purpose of this study was to determine the physicochemical properties by characterizing XRD, SEM-EDX, FTIR, and the porosity of the scaffold. The results obtained from the results of the PVA/Chitosan/CHA XRD patterns are the formation of the PVA/Chitosan phase at 2θ(°)=19.68, the IR spectrum of the 43−group band and 2 stretching, the ratio mol Ca/P is 1.98, the pore diameter is 1.561 ± 0.07 μm and the porosity is 55.04%. These results indicate that the PVA/Chitosan/CHA scaffold is an amorphous calcium phosphate (ACP) that has the potential for bone tissue engineering.

Additive Manufacturing of Iron Carbide Incorporated Bioactive Glass Scaffolds for Bone Tissue Engineering and Drug Delivery Applications.

In this study, we have synthesized a bioactive glass with composition 45SiO2-20Na2O-23CaO-6P2O5-2.5B2O3-1ZnO-2MgO-0.5CaF2 (wt %). Further, it has been incorporated with 0.4 wt % iron carbide nanoparticles to prepare magnetic bioactive glass (MBG) with good heat generation capability for potential applications in magnetic field-assisted hyperthermia. The MBG scaffolds have been fabricated using extrusion-based additive manufacturing by mixing MBG powder with 25% Pluronic F-127 solution as the binder. The saturation magnetization of iron carbide nanoparticles in the bioactive glass matrix has been found to be 80 emu/g. The morphological analysis (pore size distribution, porosity, open pore network modeling, tortuosity, and pore interconnectivity) was done using an in-house developed methodology that revealed the suitability of the scaffolds for bone tissue engineering. The compressive strength (14.3 ± 1.6 MPa) of the MBG scaffold was within the range of trabecular bone. The in vitro test using simulated body fluid (SBF) showed the formation of apatite indicating the bioactive nature of scaffolds. Further, the drug delivery behaviors of uncoated and polycaprolactone (PCL) coated MBG scaffolds have been evaluated by loading an anticancer drug (Mitomycin C) onto the scaffolds. While the uncoated scaffold demonstrated the drug's burst release for the initial 80 h, the PCL-coated scaffold showed the gradual release of the drug. These results demonstrate the potential of the proposed MBG for bone tissue engineering and drug delivery applications.

Gelatin-coated mesoporous forsterite scaffold for bone tissue engineering

This study aims to develop a mesoporous forsterite spheres-based scaffold for bone tissue regeneration. To achieve this goal, mesoporous forsterite spheres were fabricated using alginate (gel-forming agent) and activated charcoal (porogen). The impact of carbon concentration (2, 5, 10, and 20 wt %) and sintering temperature (1100 and 1200 °C) on the structural properties of mesoporous forsterite spheres was investigated. Additionally, gelatin coatings were applied to modify these spheres. Forsterite microspheres with a particle size of 2.43 ± 0.22 mm were successfully produced, exhibiting varying pore sizes based on the sintering temperature and carbon content. Notably, mesoporous forsterite spheres synthesized using 5 wt% carbon and sintered at 1200 °C displayed uniform morphology, a minor average diameter (2.4 ± 0.3 mm(, and an average pore size of 2.7 ± 0.9 μm. These optimized forsterite spheres exhibited mesoporous structures with superior surface area (2.93 m2g-1) and pore volume (0.009–0.048 cm3g-1). Furthermore, the gelatin coating, with an average thickness of 160 μm, was effectively applied to the forsterite spheres. The gelatin coating reduced the surface area (1.40 m2g-1), pore volume (0.003 cm3g-1), and average pore diameter to 9.26 nm, maintaining the mesoporous structure. Both mesoporous forsterite spheres successfully induced bone-like apatite formation in vitro during a 21-day immersion in simulated body fluid. Moreover, while both forsterite-based spheres exhibited cytocompatibility with MG63 cells (cell viability >80 %), the gelatin coating significantly enhanced osteogenic differentiation (1.29 times). In conclusion, gelatin-coated mesoporous forsterite spheres exhibit promising potential as bioactive filling scaffolds for bone tissue regeneration.

Biomimetic mineralization of platelet lysate/oxidized dextran cryogel as a macroporous 3D composite scaffold for bone repair

Scaffold development approaches using autologous sources for tissue repair are of great importance in obtaining bio-active/-compatible constructs. Platelet-rich plasma (PRP) containing various growth factors and platelet lysate (PL) derived from PRP are autologous products that have the potential to accelerate the tissue repair response by inducing a transient inflammatory event. Considering the regenerative capacity of PRP and PL, PRP/PL-based scaffolds are thought to hold great promise for tissue engineering as a natural source of autologous growth factors and a provider of mechanical support for cells. Here, a bio-mineralized PRP-based scaffold was developed using oxidized dextran (OD) and evaluated for future application in bone tissue engineering. Prepared PL/OD scaffolds were incubated in simulated body fluid (SBF) for 7, 14 and 21 d periods. Mineralized PL/OD scaffolds were characterized using Fourier transform infrared spectroscopy, x-ray diffraction spectroscopy, scanning electron microscopy (SEM), thermogravimetric analysis, porosity and compression tests. SEM and energy-dispersive x-ray spectroscopy analyses revealed mineral accumulation on the PL/OD scaffold as a result of SBF incubation. In vitro cytotoxicity and in vitro hemolysis tests revealed that the scaffolds were non-toxic and hemocompatible. Additionally, human osteoblasts (hOBs) exhibited good attachment and spreading behavior on the scaffolds and maintained their viability throughout the culture period. The alkaline phosphatase activity assay and calcium release results revealed that PL/OD scaffolds preserved the osteogenic properties of hOBs. Overall, findings suggest that mineralized PL/OD scaffold may be a promising scaffold for bone tissue engineering.

Ca-AlN MOFs-loaded chitosan/gelatin scaffolds; a dual-delivery system for bone tissue engineering applications

Creating a scaffold for bone tissue engineering that is bioactive and capable of acting as a local-dual delivery system, releasing bioactive molecules and regulating the bone remodeling process to achieve balanced bone resorption and formation, is a significant challenge. The objective of this research is to create a composite scaffold using chitosan/gelatin (CHS/Gel) and the calcium (Ca)-alendronate (ALN) metal–organic frameworks (MOFs). The scaffold will act as a dual-delivery system, releasing Ca ions and ALN to regulate bone formation. Ca-ALN MOF nanoparticles (NPs) were prepared in mild conditions and studied by FTIR, XRD, FESEM, and TGA. Ca-ALN NPs-loaded CHS/Gel scaffolds were opportunely fabricated through freeze-drying approach. Physicochemical features of the scaffolds after incorporating NPs equated by CHS/Gel scaffold changed, therefore, the attendance of NPs caused a decreasing porosity, decreased swelling, and low rate of degradation. The release profile results showed that the NPs-loaded CHS/Gel scaffolds were able to simultaneously release ALN and Ca ions due to the decomposition of NPs. Additionally, the loading of NPs in the CHS/Gel scaffold led to an increment in alkaline phosphatase (ALP) activity and the quantity of deposited Ca along with osteogenesis gene markers. These findings suggest that the NPs-loaded CHS/Gel scaffold has the potential to enhance the differentiation of human adipose tissue-derived mesenchymal stem cells, making it a promising approach for bone repair.

Sand casting-inspired surface modification of 3D-printed porous polyetheretherketone scaffolds for enhancing osteogenesis

3D-printed polyetheretherketone (PEEK) scaffolds are developed as novel bone substitutes, however, their bioinert surface hinders osteogenesis and modifying PEEK scaffolds without blocking their inter-connected porous structure is challenged. In this study, 45S5 bioactive glasses (BG) were homogeneously coated on PEEK scaffolds inspired by traditional sand-casting. The structure of PEEK scaffolds was preserved under shaping effect of BG fillers. Modulus, coating yield and hydrophilicity of scaffolds after different thermal treatment time were comparatively investigated. Excellent hydroxyapatite-forming ability of BG-coated scaffolds was confirmed by mineralization study. In-vitro assessments, BG-coated scaffolds cultured with MC3T3-E1 cells presented potential as bone implants with excellent cytocompatibility and osteogenic properties. Following similar coating strategy, conductive particles, multi-component particles and template particles were also coated on PEEK surface. The proposed methodology highlights a useful approach towards producing tunable biomedical coatings and microstructure on porous PEEK scaffolds for bone tissue engineering.

Biomimetic mineralization of 3D-printed polyhydroxyalkanoate-based microbial scaffolds for bone tissue engineering

Polyhydroxyalkanoates (PHAs) have gained much attention as a potential alternative to conventional plastic bone scaffolds due to their biocompatibility and biodegradability, among a diverse range of advantageous properties. However, the water resistance of PHA creates an environment that can interfere with cell interactions. In this study, a three-dimensional-printed PHA scaffold was fabricated through fused deposition modeling printing considering the physical properties of PHA. The PHA bone scaffolds were then coated with polydopamine (pDA) and/or hydroxyapatite (HA) in various configurations using a relatively simple and rapid process involving only immersion. The PHA–pDA– HA scaffold showed enhanced cell viability, proliferation, and differentiation, and could thus serve as a versatile platform for bone tissue engineering applications.

"Metal-bone" scaffold for accelerated peri-implant endosseous healing.

Restoring bone defects caused by conditions such as tumors, trauma, or inflammation is a significant clinical challenge. Currently, there is a need for the development of bone tissue engineering scaffolds that meet clinical standards to promote bone regeneration in these defects. In this study, we combined the porous Ti6Al4V scaffold in bone tissue engineering with advanced bone grafting techniques to create a novel "metal-bone" scaffold for enhanced bone regeneration. Utilizing 3D printing technology, we fabricated a porous Ti6Al4V scaffold with an average pore size of 789 ± 22.69μm. The characterization and biocompatibility of the scaffold were validated through in vitro experiments. Subsequently, the scaffold was implanted into the distal femurs of experimental animals, removed after 3months, and transformed into a "metal-bone" scaffold. When this "metal-bone" scaffold was re-implanted into bone defects in the animals, the results demonstrated that, in comparison to a plain porous Ti6Al4V scaffold, the scaffold containing bone tissue achieved accelerated early-stage bone regeneration. The experimental group exhibited more bone tissue generation in the early stages at the defect site, resulting in superior bone integration. In conclusion, the "metal-bone" scaffold, containing bone tissue, proves to be an effective bone-promoting scaffold with promising clinical applications.

Development of a 3D multifunctional collagen scaffold impregnated with peptide LL-37 for vascularised bone tissue regeneration

Bone is a highly dynamic connective tissue that provides structural support, locomotion and acts as a shield for many vital organs from damage. Bone inherits the ability to heal after non-severe injury. In case of severe bone abnormalities due to trauma, infections, genetic disorders and tumors, there is a demand for a scaffold that can enhance bone formation and regenerate the lost bone tissue. In this study, a 3D collagen scaffold (CS) was functionalized and assessed under in vitro and in vivo conditions. For this, a collagen scaffold coated with hydroxyapatite (Ap-CS) was developed and loaded with a peptide LL-37. The physico-chemical characterisation confirmed the hydroxyapatite coating on the outer and inner surfaces of Ap-CS. In vitro studies confirmed that LL-37 loaded Ap-CS promotes osteogenic differentiation of human osteosarcoma cells without showing significant cytotoxicity. The efficacy of the LL-37 loaded Ap-CS for bone regeneration was evaluated at 4 and 12 weeks post-implantation by histopathological and micro-CT analysis in rabbit femur defect model. The implanted LL-37 loaded Ap-CS facilitated the new bone formation at 4 weeks compared with Ap-CS without LL-37. The LL-37 loaded Ap-CS incorporating apatite and peptide LL-37 would be useful as a multifunctional scaffold for bone tissue engineering.

Ultrasound stimulated piezoelectric barium titanate and boron nitride nanotubes in nonconductive poly-ε-caprolactone nanofibrous scaffold for bone tissue engineering

Nanomaterials can provide unique solutions for the problems experienced in tissue engineering by improving a scaffold’s physico-bio-chemical properties. With its piezoelectric property, bone is an active tissue with easy adaptation and remodeling through complicated mechanisms of electromechanical operations. Although poly(ε-caprolactone) (PCL) is an excellent polymer for bone tissue engineering, it is lack of conductivity. In this study, piezoelectric barium titanates (BaTiO3) and boron nitride nanotubes (BNNTs) are used as ultrasound (US) stimulated piezoelectric components in PCL to mimic piezoelectric nature of bone tissue. Electric-responsive Human Osteoblast cells on the scaffolds were stimulated by applying low-frequency US during cell growth. Biocompatibility, cell adhesion, alkaline phosphatase activities and mineralization of osteoblast cells on piezo-composite scaffolds were investigated. BaTiO3 or BNNTs as reinforcement agents improved physical and mechanical properties of PCL scaffolds. In vitro studies show that the use of BaTiO3 or BNNTs as additives in non-conductive scaffolds significantly induces and increases the osteogenic activities even without US stimulation. Although BaTiO3 is one of the best piezoelectric materials, the improvement is more dramatic in the case of BNNTs with the increased mineralization, and excellent chemical and mechanical properties.

Augmented physical, mechanical, and cellular responsiveness of gelatin-aldehyde modified xanthan hydrogel through incorporation of silicon nanoparticles for bone tissue engineering

Bioactive scaffolds fabricated from a combination of organic and inorganic biomaterials are a promising approach for addressing defects in bone tissue engineering. In the present study, a self-crosslinked nanocomposite hydrogel, composed of gelatin/aldehyde-modified xanthan (Gel-AXG) is successfully developed by varying concentrations of porous silicon nanoparticles (PSiNPs). The effect of PSiNPs incorporation on physical, mechanical, and biological performance of the nanocomposite hydrogel is evaluated. Morphological analysis reveals formation of highly porous 3D microstructures with interconnected pores in all nanocomposite hydrogels. Increased content of PSiNPs results in a lower swelling ratio, reduced porosity and pore size, which in turn impeded media penetration and slowed down the degradation process. In addition, remarkable enhancements in dynamic mechanical properties are observed in Gel-AXG-8%Si (compressive strength: 0.6223 MPa at 90 % strain and compressive modulus: 0.054 MPa), along with improved biomineralization ability via hydroxyapatite formation after immersion in simulated body fluid (SBF). This optimized nanocomposite hydrogel provides a sustained release of Si ions at safe dose levels. Furthermore, in-vitro cytocompatibility studies using MG-63 cells exhibited remarkable performance in terms of cell attachment, proliferation, and ALP activity for Gel-AXG-8%Si. These findings suggest that the prepared nanocomposite hydrogel holds promising potential as a scaffold for bone tissue engineering.

Piezoelectrically and Topographically Engineered Scaffolds for Accelerating Bone Regeneration.

Bone regeneration remains a critical concern across diverse medical disciplines, because it is a complex process that requires a combinatorial approach involving the integration of mechanical, electrical, and biological stimuli to emulate the native cellular microenvironment. In this context, piezoelectric scaffolds have attracted considerable interest owing to their remarkable ability to generate electric fields in response to dynamic forces. Nonetheless, the application of such scaffolds in bone tissue engineering has been limited by the lack of a scaffold that can simultaneously provide both the intricate electromechanical environment and the biocompatibility of the native bone tissue. Here, we present a pioneering biomimetic scaffold that combines the unique properties of piezoelectric and topographical enhancement with the inherent osteogenic abilities of hydroxyapatite (HAp). Notably, the novelty of this work lies in the incorporation of HAp into polyvinylidene fluoride-co-trifluoro ethylene in a freestanding form, leveraging its natural osteogenic potential within a piezoelectric framework. Through comprehensive in vitro and in vivo investigations, we demonstrate the remarkable potential of these scaffolds to accelerate bone regeneration. Moreover, we demonstrate and propose three pivotal mechanisms─(i) electrical, (ii) topographical, and (iii) paracrine─that collectively contribute to the facilitated bone healing process. Our findings present a synergistically derived biomimetic scaffold design with wide-ranging prospects for bone regeneration as well as various regenerative medicine applications.

3D-Printed Graphene and Graphene Quantum Dot-Reinforced Polycaprolactone Scaffolds for Bone-Tissue Engineering

3D-Printed Graphene and Graphene Quantum Dot-Reinforced Polycaprolactone Scaffolds for Bone-Tissue Engineering

Raising the Bar: Progress in 3D-Printed Hybrid Bone Scaffolds for Clinical Applications: A Review.

Damage to bones resulting from trauma and tumors poses a significant challenge to human health. Consequently, current research in bone damage healing centers on developing three-dimensional (3D) scaffolding materials that facilitate and enhance the regeneration of fractured bone tissues. In this context, the careful selection of materials and preparation processes is essential for creating demanding scaffolds for bone tissue engineering. This is done to optimize the regeneration of fractured bones. This study comprehensively analyses the latest scientific advancements and difficulties in developing scaffolds for bone tissue creation. Initially, we clarified the composition and process by which bone tissue repairs itself. The review summarizes the primary uses of materials, both inorganic and organic, in scaffolds for bone tissue engineering. In addition, we present a comprehensive study of the most recent advancements in the mainstream techniques used to prepare scaffolds for bone tissue engineering. We also examine the distinct advantages of each method in great detail. This article thoroughly examines potential paths and obstacles in bone tissue engineering scaffolds for clinical applications.