Scaffolds For Bone Tissue Engineering Research Articles

Fabrication Strategies for Bioceramic Scaffolds in Bone Tissue Engineering with Generative Design Applications.

The aim of this study is to provide an overview of the current state-of-the-art in the fabrication of bioceramic scaffolds for bone tissue engineering, with an emphasis on the use of three-dimensional (3D) technologies coupled with generative design principles. The field of modern medicine has witnessed remarkable advancements and continuous innovation in recent decades, driven by a relentless desire to improve patient outcomes and quality of life. Central to this progress is the field of tissue engineering, which holds immense promise for regenerative medicine applications. Scaffolds are integral to tissue engineering and serve as 3D frameworks that support cell attachment, proliferation, and differentiation. A wide array of materials has been explored for the fabrication of scaffolds, including bioceramics (i.e., hydroxyapatite, beta-tricalcium phosphate, bioglasses) and bioceramic-polymer composites, each offering unique properties and functionalities tailored to specific applications. Several fabrication methods, such as thermal-induced phase separation, electrospinning, freeze-drying, gas foaming, particle leaching/solvent casting, fused deposition modeling, 3D printing, stereolithography and selective laser sintering, will be introduced and thoroughly analyzed and discussed from the point of view of their unique characteristics, which have proven invaluable for obtaining bioceramic scaffolds. Moreover, by highlighting the important role of generative design in scaffold optimization, this review seeks to pave the way for the development of innovative strategies and personalized solutions to address significant gaps in the current literature, mainly related to complex bone defects in bone tissue engineering.

Multi-parameter design of triply periodic minimal surface scaffolds: from geometry optimization to biomechanical simulation

This study introduces a multi-parameter design methodology to create triply periodic minimal surface (TPMS) scaffolds with predefined geometric characteristics. The level-set constant and unit cell lengths are systematically correlated with targeted porosity and minimum pore sizes. Network and sheet scaffolds featuring diamond, gyroid, and primitive level-set structures are generated. Three radially graded schemes are applied to each of the six scaffold type, accommodating radial variations in porosity and pore sizes. Computer simulations are conducted to assess the biomechanical performance of 18 scaffold models. Results disclose that diamond and gyroid scaffolds exhibit more expansive design ranges than primitive counterparts. While primitive scaffolds display the highest Young’s modulus and permeability, their lower yield strength and mesenchymal stem cell (MSC) adhesion render them unsuitable for bone scaffolds. Gyroid scaffolds demonstrate superior mechanical and permeability performances, albeit with slightly lower MSC adhesion than diamond scaffolds. Sheet scaffolds, characterized by more uniform material distribution, exhibit superior mechanical performance in various directions, despite slightly lower permeability. The higher specific surface area of sheet scaffolds contributes to elevated MSC adhesion. The stimulus factor analysis also revealed the superior differentiation potential of sheet scaffolds over network ones. The diamond sheet type demonstrated the optimal differentiation. Introducing radial gradations enhances axial mechanical performance at the expense of radial mechanical performance. Radially decreasing porosity displays the highest permeability, MSC adhesion, and differentiation capability, aligning with the structural characteristics of human bones. This study underscores the crucial need to balance diverse biomechanical properties of TPMS scaffolds for bone tissue engineering.

Centrifugally spun hydroxyapatite/carbon composite nanofiber scaffolds for bone tissue engineering

In recent years, advancements in tissue engineering have demonstrated the potential to expedite bone matrix formation, leading to shorter recovery times and decreased clinical challenges compared to conventional methods. Therefore, this study aims to develop composite carbon nanofibers (CNFs) integrated with nano-hydroxyapatite (nHA) particles as scaffolds for bone tissue engineering applications. A key strategy in achieving this objective involves harnessing nanofibrous structures, which offer a high surface area, coupled with nHA particles expected to accelerate bone regeneration and enhance biological activity. To realize this, polyacrylonitrile (PAN)/nHA nanofibers were fabricated using the centrifugal spinning (C-Spin) technique and subsequently carbonized to yield CNF/nHA composite structures. Scanning Electron Microscopy (SEM) confirmed C-Spin as a suitable method for PAN and CNF nanofiber production, with nHA particles uniformly dispersed throughout the nanofibrous structure. Carbonization resulted in reduced fiber diameter due to thermal decomposition and shrinkage of PAN molecules during the process. Furthermore, the incorporation of nHA particles into PAN lowered the stabilization temperature (by 5 °C–20 °C). Tensile tests revealed that PAN samples experienced an approximately 80% increase in ultimate tensile strength and a 187% increase in modulus with a 5 wt.% nHA loading. However, following carbonization, CNF samples exhibited a 50% decrease in strength compared to PAN samples. Additionally, the addition of nHA into CNF improved the graphitic structure. The incorporation of nHA particles into the spinning solution represents a viable strategy for enhancing CNF bioactivity.

Investigating mechanical properties of 3D printed porous titanium scaffolds for bone tissue engineering

Objective. Three-dimensional (3D) printed porous titanium scaffolds serve as a bone tissue engineering technology that offers a promising solution for addressing bone defects. The scaffold’s pore structure offers structural support and facilitates the proliferation of bone cells. Therefore, investigating the aperture and pore shape is of crucial for the development of 3D printed porous titanium scaffolds. Methods. Ti6Al4V scaffolds with the specified structure were fabricated using selective laser melting (SLM) technology. The scaffolds comprised fifteen cylindrical models measuring 20 mm in diameter and 20 mm in height. These models featured five scaffold shapes: imitation diamond-60°, imitation diamond-90°, imitation diamond-120°, regular tetrahedron and regular hexahedron. Each of these structural shapes was characterized by three different aperture sizes (400 μm, 600 μm and 800 μm). The porosity and mechanical properties of Ti6Al4V scaffolds were examined. Results. The measured porosity of Ti6Al4V scaffolds varied between 56.50% and 95.28%. The porosity increased with the size of the aperture. The mechanical properties tests revealed that, for identical apertures, the compressive strength and torsional strength were influenced by the configuration of the unit structure. Furthermore, the positive and lateral compressive strength as well as torsional strength of various unit structures exhibited distinct advantages and disadvantages. Within a uniform unit structure shape, the compressive strength and torsional strength were found to be correlated with the size of apertures, indicating that larger apertures result in decreased compressive and torsional strength. Conclusion. The configuration of the aperture and the shape of the pore were identified as significant factors that influenced the compressive strength. The compressive strength of Ti6Al4V scaffolds with various unit structure shapes exhibited both advantages and disadvantages when subjected to positive, lateral, and torsional forces. The enlarged aperture augmented the scaffold’s porosity while diminishing its compressive and torsional strength.

Graded or random – Effect of pore distribution in 3D titanium scaffolds on corrosion performance and response of hMSCs

Researchers agree that the ideal scaffold for tissue engineering should possess a 3D and highly porous structure, biocompatibility to encourage cell/tissue growth, suitable surface chemistry for cell attachment and differentiation, and mechanical properties that match those of the surrounding tissues. However, there is no consensus on the optimal pore distribution. In this study, we investigated the effect of pore distribution on corrosion resistance and performance of human mesenchymal stem cells (hMSC) using titanium scaffolds fabricated by laser beam powder bed fusion (PBF-LB). We designed two scaffold architectures with the same porosities (i.e., 75 %) but different distribution of pores of three sizes (200, 500, and 700 μm). The pores were either grouped in three zones (graded, GRAD) or distributed randomly (random, RAND). Microfocus X-ray computed tomography revealed that the chemically polished scaffolds had the porosity of 69 ± 4 % (GRAD) and 71 ± 4 % (RAND), and that the GRAD architecture had the higher surface area (1580 ± 101 vs 991 ± 62 mm2) and the thinner struts (221 ± 37 vs 286 ± 14 μm). The electrochemical measurements demonstrated that the apparent corrosion rate of chemically polished GRAD scaffold decreased with the immersion time extension, while that for polished RAND was increased. The RAND architecture outperformed the GRAD one with respect to hMSC proliferation (over two times higher although the GRAD scaffolds had 85 % higher initial cell retention) and migration from a monolayer. Our findings demonstrate that the pore distribution affects the biological properties of the titanium scaffolds for bone tissue engineering.

In vitro biocompatibility and stem cell regenerative assessment of hollow hydroxyapatite spheres deposited wollastonite/Ca2P6O17/TCP/doped-wollastonite scaffolds

This research examines the biological behavior of multilayer ceramic-glass scaffolds for bone tissue engineering. The scaffolds consist of a high-strength core of wollastonite and P6 (Ca2P6O17), with a sequential coating of TCP and wollastonite doped with Na+, K+ and Mg2+ ions to confer bioactivity to the system. Two formulations were investigated: a magnesium-deficient one, which served as a microstructure control, and a magnesium-rich one in which hollow hydroxyapatite (HA) spheres precipitated after one week of immersion in simulated body fluid (SBF). These formulations are denoted as C-Scaffold and HA-Scaffold, respectively. Further exploration and comparison of the physiological effects of both scaffolds is necessary to fully understand their potential as drug release agents and associated therapeutic advantages. The study considered aspects such as protein adhesion, cell morphology, and the inflammatory response. The results showed that the HA-Scaffold had over 34 % more plasma protein adhesion compared to the C-Scaffold. Similarly, cell proliferation assays showed increased cell growth in both HFF-1 fibroblasts and mesenchymal stem cells (MSCs) treated with HA-Scaffold compared to C-Scaffold. This may be attributed to the higher protein adsorption, which acts as a facilitator for cell adhesion. Three-dimensional photography from computerized microtomography confirmed that the scaffolds have a similar morphology and porosity to the intricate structure of trabecular bone in the humeral head. The study shows that the scaffolds made of Wollastonite/Ca2P6O17/TCP/Doped-Wollastonite with HA hollow spheres are highly suitable for use in this bone segment due to their overall porosity of over 86 % and approximate mechanical strength of 1.6 MPa. These findings demonstrate the biocompatibility and enhanced biological properties of the scaffolds, making them an excellent material for bone tissue engineering.

Recent Advances in 3D Printing of Smart Scaffolds for Bone Tissue Engineering and Regeneration.

The repair and functional reconstruction of bone defects resulting from severe trauma, surgical resection, degenerative disease, and congenital malformation pose significant clinical challenges. Bone tissue engineering (BTE) holds immense potential in treating these severe bone defects, without incurring prevalent complications associated with conventional autologous or allogeneic bone grafts. Three-dimensional (3D) printing technology enables control over architectural structures at multiple length scales and has been extensively employed to process biomimetic scaffolds for BTE. In contrast to inert and functional bone grafts, next-generation smart scaffolds possess remarkable ability to mimic the dynamic nature of native extracellular matrix (ECM), thereby facilitating bone repair and regeneration. Additionally, they can generate tailored and controllable therapeutic effects, such as antibacterial or antitumor properties, in response to exogenous and/or endogenous stimuli. This review provides a comprehensive assessment of the progress of 3D-printed smart scaffolds for BTE applications. It begins with an introduction to bone physiology, followed by an overview of 3D printing technologies utilized for smart scaffolds. Notable advances in various stimuli-responsive strategies, therapeutic efficacy, and applications of 3D-printed smart scaffolds are discussed. Finally, the review highlights the existing challenges in the development and clinical implementation of smart scaffolds, as well as emerging technologies in this field. This article is protected by copyright. All rights reserved.

Methacrylated Carboxymethyl Chitosan Scaffold Containing Icariin-Loaded Short Fibers for Antibacterial, Hemostasis, and Bone Regeneration.

Bone defects typically result in bone nonunion, delayed or nonhealing, and localized dysfunction, and commonly used clinical treatments (i.e., autologous and allogeneic grafts) have limited results. The multifunctional bone tissue engineering scaffold provides a new treatment for the repair of bone defects. Herein, a three-dimensional porous composite scaffold with stable mechanical support, effective antibacterial and hemostasis properties, and the ability to promote the rapid repair of bone defects was synthesized using methacrylated carboxymethyl chitosan and icariin-loaded poly-l-lactide/gelatin short fibers (M-CMCS-SFs). Icariin-loaded SFs in the M-CMCS scaffold resulted in the sustained release of osteogenic agents, which was beneficial for mechanical reinforcement. Both the porous structure and the use of chitosan facilitate the effective absorption of blood and fluid exudates. Moreover, its superior antibacterial properties could prevent the occurrence of inflammation and infection. When cultured with bone mesenchymal stem cells, the composite scaffold showed a promotion in osteogenic differentiation. Taken together, such a multifunctional composite scaffold showed comprehensive performance in antibacterial, hemostasis, and bone regeneration, thus holding promising potential in the repair of bone defects and related medical treatments.

Internal flow field analysis of a dendritic pore scaffold for bone tissue engineering

The effective reconstruction of osteochondral biomimetic structures is a key factor in guiding the regeneration of full-thickness osteochondral defects. Due to the avascular nature of hyaline cartilage, the greatest challenge in constructing this scaffold lies in both utilizing the biomimetic structure to promote vascular differentiation for nutrient delivery to hyaline cartilage, thereby enhancing the efficiency of osteochondral reconstruction, and effectively blocking vascular ingrowth into the cartilage layer to prevent cartilage mineralization. However, the intrinsic relationship between the planning of the microporous pipe network and the flow resistance in the biomimetic structure, and the mechanism of promoting cell adhesion to achieve vascular differentiation and inhibiting cell adhesion to block the growth of blood vessels are still unclear. Inspired by the structure of tree trunks, this study designed a biomimetic tree-like tubular network structure for osteochondral scaffolds based on Murray’s law. Utilizing computational fluid dynamics, the study investigated the influence of the branching angle of micro-pores on the flow velocity, pressure distribution, and scaffold permeability within the scaffold. The results indicate that when the differentiation angle exceeds 50 degrees, the highest flow velocity occurs at the confluence of tributaries at the ninth fractal position, forming a barrier layer. This structure effectively guides vascular growth, enhances nutrient transport capacity, increases flow velocity to promote cell adhesion, and inhibits cell infiltration into the cartilage layer.

3D printing of fish-scale derived hydroxyapatite/chitosan/PCL scaffold for bone tissue engineering

In the field of bone tissue repair, the treatment of bone defects has always posed a significant challenge. In recent years, the advancement of bone tissue engineering and regenerative medicine has sparked great interest in the development of innovative bone grafting materials. In this study, a novel hydroxyapatite (HA) material was successfully prepared and comprehensively characterized. Antimicrobial experiments and biological evaluations were conducted to determine its efficacy. Based on the aforementioned research findings, 3D printing technology was employed to fabricate HA/chitosan (CS)/ polycaprolactone (PCL) scaffolds. The composition of the scaffold materials was confirmed through X-ray diffractometer (XRD) and Fourier Transform Infrared Spectroscopy (FT-IR) tests, while the influence of different HA ratios on the scaffold surface morphology was observed. Additionally, antimicrobial experiments demonstrated the favorable antimicrobial activity of the scaffolds containing 30%HA + 5%CS + PCL. Furthermore, the water contact angle measurements confirmed the superhydrophilicity of the scaffolds. Finally, the excellent bioactivity and ability to promote tissue regeneration of the scaffolds were further confirmed by in vitro and in vivo experiments. This study provides new options for future repair and regeneration of bone tissue and clinical applications.

Design of chemobrionic and biochemobrionic scaffolds for bone tissue engineering

Chemobrionic systems have attracted great attention in material science for development of novel biomimetic materials. This study aims to design a new bioactive material by integrating biosilica into chemobrionic structure, which will be called biochemobrionic, and to comparatively investigate the use of both chemobrionic and biochemobrionic materials as bone scaffolds. Biosilica, isolated from Amphora sp. diatom, was integrated into chemobrionic structure, and a comprehensive set of analysis was conducted to evaluate their morphological, chemical, mechanical, thermal, and biodegradation properties. Then, the effects of both scaffolds on cell biocompatibility and osteogenic differentiation capacity were assessed. Cells attached to the scaffolds, spread out, and covered the entire surface, indicating the absence of cytotoxicity. Biochemobrionic scaffold exhibited a higher level of mineralization and bone formation than the chemobrionic structure due to the osteogenic activity of biosilica. These results present a comprehensive and pioneering understanding of the potential of (bio)chemobrionics for bone regeneration.

Fabricating oxygen self-supplying 3D printed bioactive hydrogel scaffold for augmented vascularized bone regeneration

Limited cells and factors, inadequate mechanical properties, and necrosis of defects center have hindered the wide clinical application of bone-tissue engineering scaffolds. Herein, we construct a self-oxygenated 3D printed bioactive hydrogel scaffold by integrating oxygen-generating nanoparticles and hybrid double network hydrogel structure. The hydrogel scaffold possesses the characteristics of extracellular matrix; Meanwhile, the fabricated hybrid double network structure by polyacrylamide and CaCl2-crosslinked sodium carboxymethylcellulose endows the hydrogel favorable compressive strength and 3D printability. Furthermore, the O2 generated by CaO2 nanoparticles encapsulated in ZIF-8 releases steadily and sustainably because of the well-developed microporous structure of ZIF-8, which can significantly promote cell viability and proliferation in vitro, as well as angiogenesis and osteogenic differentiation with the assistance of Zn2+. More significantly, the synergy of O2 and 3D printed pore structure can prevent necrosis of defects center and facilitate cell infiltration by providing cells the nutrients and space they need, which can further induce vascular network ingrowth and accelerate bone regeneration in all areas of the defect in vivo. Overall, this work provides a new avenue for preparing cell/factor-free bone-tissue engineered scaffolds that possess great potential for tissue regeneration and clinical alternative.

New Generation of Osteoinductive and Antimicrobial Polycaprolactone-Based Scaffolds in Bone Tissue Engineering: A Review.

With respect to other fields, bone tissue engineering has significantly expanded in recent years, leading not only to relevant advances in biomedical applications but also to innovative perspectives. Polycaprolactone (PCL), produced in the beginning of the 1930s, is a biocompatible and biodegradable polymer. Due to its mechanical and physicochemical features, as well as being easily shapeable, PCL-based constructs can be produced with different shapes and degradation kinetics. Moreover, due to various development processes, PCL can be made as 3D scaffolds or fibres for bone tissue regeneration applications. This outstanding biopolymer is versatile because it can be modified by adding agents with antimicrobial properties, not only antibiotics/antifungals, but also metal ions or natural compounds. In addition, to ameliorate its osteoproliferative features, it can be blended with calcium phosphates. This review is an overview of the current state of our recent investigation into PCL modifications designed to impair microbial adhesive capability and, in parallel, to allow eukaryotic cell viability and integration, in comparison with previous reviews and excellent research papers. Our recent results demonstrated that the developed 3D constructs had a high interconnected porosity, and the addition of biphasic calcium phosphate improved human cell attachment and proliferation. The incorporation of alternative antimicrobials-for instance, silver and essential oils-at tuneable concentrations counteracted microbial growth and biofilm formation, without affecting eukaryotic cells' viability. Notably, this challenging research area needs the multidisciplinary work of material scientists, biologists, and orthopaedic surgeons to determine the most suitable modifications on biomaterials to design favourable 3D scaffolds based on PCL for the targeted healing of damaged bone tissue.

Customized 3D printed porous titanium scaffolds with nanotubes loading antibacterial drugs for bone tissue engineering

Abstract Due to the uncertainty of trauma or infection, customized bone substitutes are often required in clinic. Meanwhile, excessive use of antibiotics may lead to drug resistance. Therefore, the design of anti-infection bone tissue engineering scaffold is of very important. In this study, porous titanium alloy bone tissue engineering scaffolds were designed and fabricated by 3D printing. TiO2 nanotubes were further constructed on the scaffolds through electrochemical anodic oxidation, achieving the drug loading and anti-infection functions. The micron-level bionic pores were fabricated by the 3D printing process, and the secondary nanoscale-level nanotubes were achieved through the anodic oxidation process. Thereafter, the micro–nano structured porous bone tissue engineering scaffolds are presented. This structure features that the drug release rate can be regulated by loading the anti-infection drug minocycline and coating them with poly(lactic-co-glycolic acid) (PLGA) in the nanotubes. According to the results, the micro–nano composite porous scaffold showed uniform and controllable micro–nano pores, it may load anti-infection drugs and shown anti-infection ability. In addition, the PLGA coating may delay the drug release and maintain a sustained anti-infection function for the scaffold in a week. This study provides new ideas for designing antibacterial bone tissue engineering scaffold.

Application and Development of Electrospun Nanofiber Scaffolds for Bone Tissue Engineering.

Nanofiber scaffolds have gained significant attention in the field of bone tissue engineering. Electrospinning, a straightforward and efficient technique for producing nanofibers, has been extensively researched. When used in bone tissue engineering scaffolds, electrospun nanofibers with suitable surface properties promote new bone tissue growth and enhance cell adhesion. Recent advancements in electrospinning technology have provided innovative approaches for scaffold fabrication in bone tissue engineering. This review comprehensively examines the utilization of electrospun nanofibers in bone tissue engineering scaffolds and evaluates the relevant literature. The review begins by presenting the fundamental principles and methodologies of electrospinning. It then discusses various materials used in the production of electrospun nanofiber scaffolds for bone tissue engineering, including natural and synthetic polymers, as well as certain inorganic materials. The challenges associated with these materials are also described. The review focuses on novel electrospinning techniques for scaffold construction in bone tissue engineering, such as multilayer nanofibers, multifluid electrospinning, and the integration of electrospinning with other methods. Recent advancements in electrospinning technology have enabled the fabrication of precisely aligned nanofiber scaffolds with nanoscale architectures. These innovative methods also facilitate the fabrication of biomimetic structures, wherein bioactive substances can be incorporated and released in a controlled manner for drug delivery purposes. Moreover, they address issues encountered with traditional electrospun nanofibers, such as mechanical characteristics and biocompatibility. Consequently, the development and implementation of novel electrospinning technologies have revolutionized scaffold fabrication for bone tissue engineering.

Modified five times simulated body fluid for efficient biomimetic mineralization

Simulated body fluid (SBF) is widely utilized in preclinical research for estimating the mineralization efficacy of biomaterials. Therefore, it is of great significance to construct an efficient and stable SBF mineralization system. The conventional SBF solutions cannot maintain a stable pH value and are prone to precipitate homogeneous calcium salts at the early stages of the biomimetic process because of the release of gaseous CO2. In this study, a simple but efficient five times SBF buffered by 5 % CO2 was developed and demonstrated to achieve excellent mineralized microstructure on a type of polymer-aligned nanofibrous scaffolds, which is strikingly similar to the natural human bone tissue. Scanning electron microscopy and energy-dispersive X-ray examinations indicated the growth of heterogeneous apatite with a high-calcium-to-phosphate ratio on the aligned nanofibers under 5 times SBF buffered by 5 % CO2. Moreover, X-ray diffraction spectroscopy and Fourier transform infrared analyses yielded peaks associated with carbonated hydroxyapatite with less prominent crystallization. In addition, the biomineralized aligned polycaprolactone nanofibers demonstrated excellent cell attachment, alignment, and proliferation characteristics in vitro. Overall, the results of this study showed that 5 × SBFs buffered by 5 % CO2 partial pressure are attractive alternatives for the efficient biomineralization of scaffolds in bone tissue engineering, and could be used as a model for the prediction of the bone-bonding bioactivity of biomaterials.

Fabrication of 3D chitosan/polyvinyl alcohol/brushite nanofibrous scaffold for bone tissue engineering by electrospinning using a novel falling film collector

Despite its advantages, electrospinning has limited effectiveness in 3D scaffolding due to the high density of fibers it produces. In this research, a novel electrospinning collector was developed to overcome this constraint. An aqueous suspension containing chitosan/polyvinyl alcohol nanofibers was prepared employing a unique falling film collector. Suspension molding by freeze-drying resulted in a 3D nanofibrous scaffold (3D-NF). The mineralized scaffold was obtained by brushite deposition on 3D-NF using wet chemical mineralization by new sodium tripolyphosphate and calcium chloride dihydrate precursors. The 3D-NF was optimized and compared with the conventional electrospun 2D nanofibrous scaffold (2D-NF) and the 3D freeze-dried scaffold (3D-FD). Both minor fibrous and major freeze-dried pore shapes were present in 3D-NFs with sizes of 16.11–24.32 μm and 97.64–234.41 μm, respectively. The scaffolds' porosity increased by 53 % to 73 % compared to 2D-NFs. Besides thermal stability, mineralization improved the 3D-NF's ultimate strength and elastic modulus by 2.2 and 4.7 times, respectively. In vitro cell studies using rat bone marrow mesenchymal cells confirmed cell infiltration up to 290 μm and scaffold biocompatibility. The 3D-NFs given nanofibers and brushite inclusion exhibited considerable osteoinductivity. Therefore, falling film collectors can potentially be applied to prepare 3D-NFs from electrospinning without post-processing.

Bone Morphogenetic Protein 7-Loaded Gelatin Methacrylate/Oxidized Sodium Alginate/Nano-Hydroxyapatite Composite Hydrogel for Bone Tissue Engineering.

Bone tissue engineering (BTE) is a promising alternative to autologous bone grafting for the clinical treatment of bone defects, and inorganic/organic composite hydrogels as BTE scaffolds are a hot spot in current research. The construction of nano-hydroxyapatite/gelatin methacrylate/oxidized sodium alginate (nHAP/GelMA/OSA), abbreviated as HGO, composite hydrogels loaded with bone morphogenetic protein 7 (BMP7) will provide a suitable 3D microenvironment to promote cell aggregation, proliferation, and differentiation, thus facilitating bone repair and regeneration. Dually-crosslinked hydrogels were fabricated by combining GelMA and OSA, while HGO hydrogels were formulated by incorporating varying amounts of nHAP. The hydrogels were physically and chemically characterized followed by the assessment of their biocompatibility. BMP7-HGO (BHGO) hydrogels were fabricated by incorporating suitable concentrations of BMP7 into HGO hydrogels. The osteogenic potential of BHGO hydrogels was then validated through in vitro experiments and using rat femoral defect models. The addition of nHAP significantly improved the physical properties of the hydrogel, and the composite hydrogel with 10% nHAP demonstrated the best overall performance among all groups. The selected concentration of HGO hydrogel served as a carrier for BMP7 loading and was evaluated for its osteogenic potential both in vivo and in vitro. The BHGO hydrogel demonstrated superior in vitro osteogenic induction and in vivo potential for repairing bone tissue compared to the outcomes observed in the blank control, BMP7, and HGO groups. Using hydrogel containing 10% HGO appears promising for bone tissue engineering scaffolds, especially when loaded with BMP7 to boost its osteogenic potential. However, further investigation is needed to optimize the GelMA, OSA, and nHAP ratios, along with the BMP7 concentration, to maximize the osteogenic potential.

Production of Agarose-Hydroxyapatite Composites via Supercritical Gel Drying, for Bone Tissue Engineering.

Bone tissue engineering (BTE) is the most promising strategy to repair bones injuries and defects. It relies on the utilization of a temporary support to host the cells and promote nutrient exchange (i.e., the scaffold). Supercritical CO2 assisted drying can preserve scaffold nanostructure, crucial for cell attachment and proliferation. In this work, agarose aerogels, loaded with hydroxyapatite were produced in view of BTE applications. Different combinations of agarose concentration and hydroxyapatite loadings were tested. FESEM and EDX analyses showed that scaffold structure suffered from partial closure when increasing filler concentration; hydroxyapatite distribution was homogenous, and Young's modulus improved. Looking at BTE applications, the optimal combination of agarose and hydroxyapatite resulted to be 1% w/w and 10% w/v, respectively. Mechanical properties showed that the produced composites could be eligible as starting scaffold for BTE, with a Young's Modulus larger than 100 kPa for every blend.

TPMS Microarchitectures for Vertical Bone Augmentation and Osteoconduction: An In Vivo Study.

Triply periodic minimal surface microarchitectures (TPMS) were developed by mathematicians and evolved in all kingdoms of living organisms. Renowned for their lightweight yet robust attributes, TPMS structures find application in diverse fields, such as the construction of satellites, aircrafts, and electric vehicles. Moreover, these microarchitectures, despite their intricate geometric patterns, demonstrate potential for application as bone substitutes, despite the inherent gothic style of natural bone microarchitecture. Here, we produced three TPMS microarchitectures, D-diamond, G-gyroid, and P-primitive, by 3D printing from hydroxyapatite. We explored their mechanical characterization and, further, implanted them to study their bone augmentation and osteoconduction potential. In terms of strength, the D-diamond and G-gyroid performed significantly better than the P-primitive. In a calvarial defect model and a calvarial bone augmentation model, where osteoconduction is determined as the extent of bony bridging of the defect and bone augmentation as the maximal vertical bone ingrowth, the G-gyroid performed significantly better than the P-primitive. No significant difference in performance was observed between the G-gyroid and D-diamond. Since, in real life, the treatment of bone deficiencies in patients comprises elements of defect bridging and bone augmentation, ceramic scaffolds with D-diamond and G-gyroid microarchitectures appear as the best choice for a TPMS-based scaffold in bone tissue engineering.