Fabrication Of Scaffolds Research Articles

3D-Printed Silk Proteins for Bone Tissue Regeneration and Associated Immunomodulation.

Current bone repair methods have limitations, prompting the exploration of innovative approaches. Tissue engineering emerges as a promising solution, leveraging biomaterials to craft scaffolds replicating the natural bone environment, facilitating cell growth and differentiation. Among fabrication techniques, three-dimensional (3D) printing stands out for its ability to tailor intricate scaffolds. Silk proteins (SPs), known for their mechanical strength and biocompatibility, are an excellent choice for engineering 3D-printed bone tissue engineering (BTE) scaffolds. This article comprehensively reviews bone biology, 3D printing, and the unique attributes of SPs, specifically detailing criteria for scaffold fabrication such as composition, structure, mechanics, and cellular responses. It examines the structural, mechanical, and biological attributes of SPs, emphasizing their suitability for BTE. Recent studies on diverse 3D printing approaches using SPs-based for BTE are highlighted, alongside advancements in their 3D and four-dimensional (4D) printing and their role in osteo-immunomodulation. Future directions in the use of SPs for 3D printing in BTE are outlined.

Reliable Fabrication of Mineral-Graded Scaffolds by Spin-Coating and Laser Machining for Use in Tendon-to-Bone Insertion Repair.

A reliable method for fabricating biomimetic scaffolds with a controllable mineral gradient to facilitate the surgical repair of tendon-to-bone injuries and the regeneration of the enthesis is reported. The gradient in mineral content is created by sequentially spin-coating with hydroxyapatite/poly(ε-caprolactone) suspensions containing hydroxyapatite nanoparticles in decreasing concentrations. To produce pores and facilitate cell infiltration, the spin-coated film is released and patterned with an array of funnel-shaped microchannels by laser machining. The unique design provided both mechanical (i.e., substrate stiffness) and biochemical (e.g., hydroxyapatite content) cues to spatially control the graded differentiation of mesenchymal stem cells. Immunocytochemical analysis of human mesenchymal stem cell-seeded scaffolds after 14 days of culture demonstrated the formation of a spatial phenotypic cell gradient from osteoblasts to mineralized chondrocytes based on the level of mineralization in the scaffold. By successfully recreating compositional and cellular features of the native tendon enthesis, the biomimetic scaffolds offer a promising avenue for improved tendon-to-bone repair.

Endogenous Tissue Engineering for Chondral and Osteochondral Regeneration: Strategies and Mechanisms.

Increasing attention has been paid to the development of effective strategies for articular cartilage (AC) and osteochondral (OC) regeneration due to their limited self-reparative capacities and the shortage of timely and appropriate clinical treatments. Traditional cell-dependent tissue engineering faces various challenges such as restricted cell sources, phenotypic alterations, and immune rejection. In contrast, endogenous tissue engineering represents a promising alternative, leveraging acellular biomaterials to guide endogenous cells to the injury site and stimulate their intrinsic regenerative potential. This review provides a comprehensive overview of recent advancements in endogenous tissue engineering strategies for AC and OC regeneration, with a focus on the tissue engineering triad comprising endogenous stem/progenitor cells (ESPCs), scaffolds, and biomolecules. Multiple types of ESPCs present within the AC and OC microenvironment, including bone marrow-derived mesenchymal stem cells (BMSCs), adipose-derived mesenchymal stem cells (AD-MSCs), synovial membrane-derived mesenchymal stem cells (SM-MSCs), and AC-derived stem/progenitor cells (CSPCs), exhibit the ability to migrate toward injury sites and demonstrate pro-regenerative properties. The fabrication and characteristics of scaffolds in various formats including hydrogels, porous sponges, electrospun fibers, particles, films, multilayer scaffolds, bioceramics, and bioglass, highlighting their suitability for AC and OC repair, are systemically summarized. Furthermore, the review emphasizes the pivotal role of biomolecules in facilitating ESPCs migration, adhesion, chondrogenesis, osteogenesis, as well as regulating inflammation, aging, and hypertrophy-critical processes for endogenous AC and OC regeneration. Insights into the applications of endogenous tissue engineering strategies for in vivo AC and OC regeneration are provided along with a discussion on future perspectives to enhance regenerative outcomes.

Production of platelet-rich plasma (PRP)-enriched scaffolds for bone tissue regeneration with 3D printing technology

Bone disorders signify diverse abnormalities in the structure, development, and functions of bone tissue in the human body, with a significant correlation to ageing, insufficient physical activity, and escalating obesity. Recent advancements in bone tissue engineering aim to enhance bone tissue formation through the use of biomaterials, growth factors, and cells. The present study focuses on the fabrication and characterisation of scaffolds with a composition of gelatin (GEL) / sodium alginate (SA) / hydroxyapatite (HA) / platelet-rich plasma (PRP) using the 3D printing process. The inclusion of PRP, derived from blood, is of particular interest due to its potential to enhance bone regeneration through various growth factors. Scanning electron microscope (SEM) analysis revealed average pore sizes ranging from 481.50 ± 7.65 to 623.96 ± 11.54 µm. SEM images also showed that scaffold surfaces became smooth as the concentration of PRP increased. The mechanical test results demonstrated that as the PRP increased, the compressive strength decreased. When the swelling and degradation behaviours of scaffolds were examined, it was observed that GEL/SA/HA/3PRP scaffolds exhibited approximately 200 % swelling capability until the 4th day. GEL/SA/HA scaffolds showed a degradation behaviour about 70 % higher compared to other groups. A controlled release profile of PRP was maintained up to the 144th, 216th, and 240th hours from the scaffolds. According to the highest correlation coefficients (R2) in the release kinetics of scaffolds, GEL/SA/HA/0.5PRP and GEL/SA/HA/1PRP scaffolds were explained by the first-order model. In contrast, the GEL/SA/HA/3PRP scaffold was described using the Korsmeyer–Peppas model. The MTT analysis conducted with osteoblast cells showed that scaffolds did not demonstrate any toxic effects and facilitated cell adhesion by inducing the formation of extensions. These findings underscore the potential of PRP-incorporated GEL/SA/HA composites as a promising approach for bone tissue engineering, offering significant advancements in the treatment of bone disorders. This could lead to more effective treatments for bone disorders and injuries, reducing the need for more invasive procedures and improving patient recovery times.

A 3D bioprinted antibacterial hydrogel dressing of gelatin/sodium alginate loaded with ciprofloxacin hydrochloride.

Skin plays a crucial role in human physiological functions, however, it was vulnerable to bacterial infection which delayed wound healing. Nowadays, designing an individual wound dressing with good biocompatibility and sustaining anti-infection capability for healing of chronic wounds are still challenging. In this study, various concentrations of the ciprofloxacin (CIP) were mixed with gelatine (Gel)/sodium alginate (SA) solution to prepare Gel/SA/CIP (GAC) bioinks, following the fabrication of GAC scaffold by an extrusion 3D bioprinting technology. The results showed that the GAC bioinks had good printability and the printed GAC scaffolds double-crosslinked by EDC/NHS and CaCl2 had rich porous structure with appropriate pore size, which were conducive to drug release and cell growth. It demonstrated that the CIP could be rapidly released by 70% in 5min, which endowed the GAC composite scaffolds with an excellent antibacterial ability. Especially, the antibacterial activities of GAC7.5 against Escherichia coli and Staphylococcus aureus within 24h were even close to 100%, and the inhibition zones were still maintained 14.78±0.40mm and 14.78±0.40mm, respectively, after 24h. Meanwhile, GAC7.5 also demonstrated impressive biocompatibility which can promote the growth and migration of L929 and accelerate wound healing. Overall, the GAC7.5 3D bioprinting scaffold could be used as a potential skin dressing for susceptible wounds with excellent antibacterial activity and good biocompatibility to meet urgent clinical needs.

Material extrusion additive manufacturing of graphene oxide reinforced 13–93B1 bioactive glass scaffolds for bone tissue engineering applications

Graphene-reinforced bioactive glass scaffolds have gained significant attention in the field of bone tissue engineering due to their unique combination of mechanical strength, bioactivity, and electrical conductivity. Additive manufacturing techniques, such as 3D printing, provide a versatile platform for fabricating these scaffolds with precise control over their architecture and composition. Consequently, in this work, we have fabricated graphene oxide (GO)-reinforced 13–93B1 bioactive glass scaffold using the material extrusion-based additive manufacturing. A Pluronic F-127-based ink was prepared for scaffold fabrication, and its rheological properties were assessed for shear thinning behaviour, structural support, and recovery. Further, the fabricated scaffolds were characterized using micro-computed tomography, scanning electron microscopy, and energy dispersive x-ray spectroscopy. Additionally, computational fluid dynamics simulations with Dulbecco’s modified eagle medium and blood were performed to evaluate the perfusion kinetics of the scaffolds. The inclusion of GO enhanced the compressive strength of the fabricated scaffolds by ∼202 %. The morphological characterization based on micro-computed tomography showed that additively manufactured scaffolds have appropriate porosity, pore size, pore throat size, and interconnectivity for bone tissue engineering. The synergy with surrounding muscle tissue is also crucial for scaffold-guided bone regeneration. A scaffold supporting the muscle growth around the bone will be able to promote bone-muscle crosstalk and, in turn, bone regeneration. The live-dead assay results showed no cytotoxicity towards C2C12 mouse myoblast cells. Also, cell adhesion and cell viability results show better cell growth on the nanocomposite scaffolds. Overall, the fabricated scaffolds are found suitable for bone tissue engineering applications.

Biomimetic scaffold and 3D bioprinting in dental application: A review.

Biomimetic scaffold and 3D bioprinting technologies have emerged as promising avenues in tissue engineering and regenerative medicine, offering innovative approaches to address the limitations of conventional tissue engineering methods. This review article provides a comprehensive overview of recent advancements, challenges, and future prospects in the field of biomimetic scaffold fabrication and 3D bioprinting techniques.

Fatigue Performance of 3D-Printed Poly-Lactic-Acid Bone Scaffolds with Triply Periodic Minimal Surface and Voronoi Pore Structures.

Bone scaffolds serve a crucial role in tissue engineering, particularly in facilitating bone regeneration where natural repair is insufficient. Despite advancements in the fabrication of polymeric bone scaffolds, the challenge remains to optimize their mechanical resilience. Specifically, research on the fatigue behaviour of polymeric bone scaffolds is scarce. This study investigates the influence of pore architecture on the mechanical performance of poly-lactic-acid (PLA) scaffolds under quasi-static and cyclic compression. PLA scaffolds with a 60% porosity were fabricated using extrusion-based 3D printing in various designs: Gyroid, Lidinoid, Fischer-Koch, IWP, and Voronoi. Results demonstrated that Gyroid scaffolds had the highest compressive strength (6.6 MPa), followed by Lidinoid, Fischer-Koch, IWP, and Voronoi designs. Increased strut thickness was linked to higher compressive strength. However, normalized fatigue resistance showed a different pattern. While scaffolds resisted fatigue cycles at low strain amplitudes, fatigue damage was observed at higher strains. Voronoi structures exhibited the highest normalized fatigue performance, enduring around 58,000 cycles at 85% strain amplitude, followed by Gyroid, Fischer-Koch, Lidinoid, and IWP structures. Enhanced fatigue performance in different topologies correlated with the minimum cross-sectional area of scaffolds. Given the importance of both static and fatigue strength, the Gyroid topology emerges as the superior choice overall.

A study on the synergistic chondro-inductive effects of collagen II and its high-resolution 3D-printed scaffolds

Collagen II is the most essential component of the cartilage-specific extracellular matrix (ECM). However, research on collagen II-based scaffold fabrication, structural optimization, and correlation to the chondrogenic activities of stem cells is currently limited, presumably due to challenges related to its hydrogel processability. Existing collagen II-containing scaffolds are mainly produced by freeze-drying and exhibit limited properties, such as pore interconnectivity and tortuosity. Additionally, the chondro-inductive capability of collagen II composition and its underlying mechanism remains unclear, warranting further research. In this study, we addressed the aforementioned issues by investigating and enhancing the rheological properties of collagen II-based hydrogel, resulting in a high printing resolution exceeding 150 μm. The collagen II composition reportedly facilitated the condensation and chondrogenic activities of mesenchymal stem cells (MSCs) compared to gelatin. Moreover, high-resolution collagen II-based scaffolds promoted cell proliferation and chondrogenic differentiation to a higher degree. Therefore, we optimized the compositional and structural characteristics of collagen II-based scaffolds for enhancing chondrogenic activities. We anticipate that this study will broaden our understanding of collagen II-based scaffold designs and condition optimizations for cartilage tissue engineering.

Multilayered hydrogel scaffold construct with native tissue matched elastic modulus: A regenerative microenvironment for urethral scar-free healing

The unsuitable deformation stimulus, harsh urine environment, and lack of a regenerative microenvironment (RME) prevent scaffold-based urethral repair and ultimately lead to irreversible urethral scarring. The researchers clarify the optimal elastic modulus of the urethral scaffolds for urethral repair and design a multilayered PVA hydrogel scaffold for urethral scar-free healing. The inner layer of the scaffold has self-healing properties, which ensures that the wound effectively resists harsh urine erosion, even when subjected to sutures. In addition, the scaffold's outer layer has an extracellular matrix-like structure that synergizes with adipose-derived stem cells to create a favorable RME. In vivo experiments confirm successful urethral scar-free healing using the PVA multilayered hydrogel scaffold. Further mechanistic study shows that the PVA multilayer hydrogel effectively resists the urine-induced inflammatory response and accelerates the transition of urethral wound healing to the proliferative phase by regulating macrophage polarization, thus providing favorable conditions for urethral scar-free healing. This study provides mechanical criteria for the fabrication of urethral tissue-engineered scaffolds, as well as important insights into their design.

Cardiac Tissue Engineering: A Journey from Scaffold Fabrication to In Vitro Characterization

Cardiac tissue engineering has been rapidly evolving with diverse applications, ranging from the repair of fibrotic tissue caused by “adverse remodeling,” to the replacement of specific segments of heart tissue, and ultimately to the creation of a whole heart. The repair or replacement of cardiac tissue often involves the development of tissue scaffolds or constructs and the subsequent assessment of their performance and functionality. For this, the design and/or selection of biomaterials, and cell types, scaffold fabrication, and in vitro characterizations are the first starting points, yet critical, to ensure success in subsequent implantation in vivo. This highlights the importance of scaffold fabrication and in vitro experiments/characterization with protocols for cardiac tissue engineering. Yet, a comprehensive and critical review of these has not been established and documented. As inspired, herein, the latest development and advances in scaffold fabrication and in vitro characterization for cardiac tissue engineering are critically reviewed, with focus on biomaterials, cell types, additive manufacturing techniques for scaffold fabrication, and common in vitro characterization techniques or methods. This article would be of benefit to the ones who are working on cardiac tissue engineering by providing insights into the scaffold fabrication and in vitro investigations.

Photo-Clickable Triazine-Trione Thermosets as Promising 3D Scaffolds for Tissue Engineering Applications.

There is an overwhelming demand for new scaffolding materials for tissue engineering (TE) purposes. Polymeric scaffolds have been explored as TE materials; however, their high glass transition state (Tg) limits their applicability. In this study, a novel materials platform for fabricating TE scaffolds is proposed based on solvent-free two-component heterocyclic triazine-trione (TATO) formulations, which cure at room temperature via thiol-ene/yne photochemistry. Three ester-containing thermosets, TATO-1, TATO-2, and TATO-3, are used for the fabrication of TE scaffolds including rigid discs, elastic films, microporous sponges, and 3D printed objects. After 14 days' incubation the materials covered a wide range of properties, from the soft TATO-2 having a compression modulus of 19.3MPa and a Tg of 30.4°C to the hard TATO-3 having a compression modulus of 411MPa and a Tg of 62.5°C. All materials exhibit micro- and nano-surface morphologies suited for bone tissue engineering, and in vitro studies found them all to be cytocompatible, supporting fast cell proliferation while minimizing cell apoptosis and necrosis. Moreover, bone marrow-derived mesenchymal stem cells on the surface of the materials are successfully differentiated into osteoblasts, adipocytes, and neuronal cells, underlining the broad potential for the biofabrication of TATO materials for TE clinical applications.

Bioactive Glass in Tissue Regeneration: Unveiling Recent Advances in Regenerative Strategies and Applications.

Bioactive glass (BG) is a class of biocompatible, biodegradable, multifunctional inorganic glass materials, which is successfully used for orthopedic and dental applications, with several products already approved for clinical use. Apart from exhibiting osteogenic properties, BG is also known to be angiogenic and antibacterial. Recently, BG's role in immunomodulation has been gradually revealed. While the therapeutic effect of BG is mostly reported in the context of bone and skin-related regeneration, its application in regenerating other tissues/organs, such as muscle, cartilage, and gastrointestinal tissue, has also been explored recently. The strategies of applying BG have also expanded from powder or cement form to more advanced strategies such as fabrication of composite polymer-BG scaffold, 3D printing of BG-loaded scaffold, and BG-induced extracellular vesicle production. This review presents a concise overview of the recent applications of BG in regenerative medicine. Various regenerative strategies of BG will be first introduced. Next, the applications of BG in regenerating various tissues/organs, such as bone, cartilage, muscle, tendon, skin, and gastrointestinal tissue, will be discussed. Finally, summarizing clinical applications of BG for tissue regeneration will conclude, and outline future challenges and directions for the clinical translation of BG.

A Systematic Review on the Generation of Organic Structures through Additive Manufacturing Techniques.

Additive manufacturing (AM) has emerged as a transformative technology in the fabrication of intricate structures, offering unparalleled adaptability in crafting complex geometries. Particularly noteworthy is its burgeoning significance within the realm of medical prosthetics, owing to its capacity to seamlessly replicate anatomical forms utilizing biocompatible materials. Notably, the fabrication of porous architectures stands as a cornerstone in orthopaedic prosthetic development and bone tissue engineering. Porous constructs crafted via AM exhibit meticulously adjustable pore dimensions, shapes, and porosity levels, thus rendering AM indispensable in their production. This systematic review ventures to furnish a comprehensive examination of extant research endeavours centred on the generation of porous scaffolds through additive manufacturing modalities. Its primary aim is to delineate variances among distinct techniques, materials, and structural typologies employed, with the overarching objective of scrutinizing the cutting-edge methodologies in engineering self-supported stochastic printable porous frameworks via AM, specifically for bone scaffold fabrication. Findings show that most of the structures analysed correspond to lattice structures. However, there is a strong tendency to use organic structures generated by mathematical models and printed using powder bed fusion techniques. However, no work has been found that proposes a self-supporting design for organic structures.

Chondroitin Sulfate and Hyaluronic Acid-Based PolyHIPE Scaffolds for Improved Osteogenesis and Chondrogenesis In Vitro.

Osteochondral damage, affecting the articular cartilage and the underlying subchondral bone, presents significant challenges in clinical treatment. Such defects, commonly seen in knee and ankle joints, vary from small localized lesions to larger defects. Current medical therapies encounter several challenges, such as donor shortages, drug side effects, high costs, and rejection problems, often resulting in only temporary relief. Highly porous emulsion-templated polymers (polyHIPEs) offer numerous potential benefits in the fabrication of scaffolds for tissue engineering and regenerative medicine. Polymeric scaffolds synthesized using a high internal phase emulsion (HIPE) technique, called PolyHIPEs, involve polymerizing a continuous phase surrounding a dispersed internal phase to form a solid, foam-like structure. A dense, porous design encourages cell ingrowth, nutrient delivery, and waste disposal from the scaffold, mimicking the cells' natural microenvironment. This study used hydroxyethyl methacrylate (HEMA) and acrylamide (AAM) polyHIPE scaffolds combined with extracellular matrix (ECM) components of the tissue, such as methacrylated hyaluronic acid (MHA) and methacrylated chondroitin sulfate (MCS), to prepare polyHIPE scaffolds. The mouse preosteoblast MC3T3-E1 cells and primary rat chondrocytes (harvested from male Wistar rats) were seeded on the scaffolds and cultured for 21 days to assess the osteogenesis and chondrogenesis in vitro. When compared to the AAM-MHA and AAM-MCS groups at day 21, scaffold groups HEMA-MHA and HEMA-MCS showed a significant rise in alkaline phosphatase (ALP) and calcium content. Chondrogenic markers such as glycosaminoglycan (GAG) and hydroxyproline were also assessed over a 21-day time point. On day 21, it was found that GAG and hydroxyproline production were considerably higher in the HEMA-MHA and HEMA-MCS scaffolds than in the AAM-MHA and AAM-MCS scaffolds. The overall studies showed that polyHIPE monolith scaffolds could favor cell adherence, survival ability, proliferation, differentiation, and ECM formation over 21 days. Thus, incorporating ECM components enhanced osteogenesis and chondrogenesis in vitro and can be further used as tissue repair models.

Antibacterial and Osteogenic Dual-Functional Micronano Composite Scaffold Fabricated via Melt Electrowriting and Solution Electrospinning for Bone Tissue Engineering.

The utilization of micronano composite scaffolds has been extensively demonstrated to confer the superior advantages in bone repair compared to single nano- or micron-sized scaffolds. Nevertheless, the enhancement of bioactivities within these composite scaffolds remains challenging. In this study, we propose a novel approach to combine melt electrowriting (MEW) and solution electrospinning (SES) techniques for the fabrication of a composite scaffold incorporating hydroxyapatite (HAP), an osteogenic component, and roxithromycin (ROX), an antibacterial active component. Scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR) confirmed the hierarchical architecture of the nanofiber-microgrid within the scaffold, as well as the successful loading of HAP and ROX. The incorporation of HAP enhanced the water absorption capacity of the composite scaffold, thus promoting cell adhesion and proliferation, as well as osteogenic differentiation. Furthermore, ROX resulted in effective antibacterial capability without any observable cytotoxicity. Finally, the scaffolds were applied to a rat calvarial defect model, and the results demonstrated that the 20% HAP group exhibited superior new bone formation without causing adverse reactions. Therefore, our findings present a promising strategy for designing and fabricating bioactive scaffolds for bone regeneration.

Fabrication of polymer-based bone scaffolds—Conventional vs. advanced methods

Fabrication of polymer-based bone scaffolds—Conventional vs. advanced methods

3D Printing and Surface Engineering of Ti6Al4V Scaffolds for Enhanced Osseointegration in an In Vitro Study.

Ti6Al4V superalloy is recognized as a good candidate for bone implants owing to its biocompatibility, corrosion resistance, and high strength-to-weight ratio. While dense metal implants are associated with stress shielding issues due to the difference in densities, stiffness, and modulus of elasticity compared to bone tissues, the surface of the implant/scaffold should mimic the properties of the bone of interest to assure a good integration with a strong interface. In this study, we investigated the additive manufacturing of porous Ti6Al4V scaffolds and coating modification for enhanced osteoconduction using osteoblast cells. The results showed the successful fabrication of porous Ti6Al4V scaffolds with adequate strength. Additionally, the surface treatment with NaOH and Dopamine Hydrochloride (DOPA) promoted the formation of Dopamine Hydrochloride (DOPA) coating with an optimized coating process, providing an environment that supports higher cell viability and growth compared to the uncoated Ti6Al4V scaffolds, as demonstrated by the higher proliferation ratios observed from day 1 to day 29. These findings bring valuable insights into the surface modification of 3D-printed scaffolds for improved osteoconduction through the coating process in solutions.

A Comprehensive Literature Review on Advancements and Challenges in 3D Bioprinting of Human Organs: Ear, Skin, and Bone.

The field of 3D bioprinting is rapidly emerging within the realm of regenerative medicine, offering significant potential in dealing with the issue of organ shortages. Despite being in its early stages, it has the potential to replicate tissue structures accurately, providing new potential solutions for reconstructive surgery. This review explores the diverse applications of 3D bioprinting in regenerative medicine, pharmaceuticals, and the food industry, specifically focusing on ear, skin, and bone tissues due to their unique challenges and implications in the field. Significant progress has been made in cartilage and bone scaffold fabrication in ear reconstruction, yet challenges in functional maturation persist. Recent advancements highlight the potential for patient-specific ear substitutes, emphasizing the need for extensive clinical trials. In skin regeneration, 3D bioprinting addresses limitations in existing models, offering opportunities for improved wound healing and realistic skin models. While challenges exist, progress in biomaterials and in-situ bioprinting holds promise. In bone regeneration, 3D bioprinting presents personalized solutions for defects, but scaffold design refinement and addressing regulatory and ethical considerations are crucial. The transformative potential of 3D bioprinting in the field of medicine holds the promise of redefining therapeutic approaches and delivering personalized treatments and functional tissues. Interdisciplinary collaboration is essential for fully realizing the capabilities of 3D bioprinting. This review provides a detailed analysis of current methodologies, challenges, and prospects in 3D bioprinting for ear, skin, and bone tissue regeneration.

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.