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Treating large bone defects, known as critical-sized defects (CSDs), is challenging because they are not spontaneously healed by the patient’s body. Due to the limitations associated with conventional bone grafts, bone tissue engineering (BTE), based on three-dimensional (3D) bioprinted scaffolds, has emerged as a promising approach for bone recons...
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Bone defects have caused immense healthcare concerns and economic burdens throughout the world. Traditional autologous allogeneic bone grafts have many drawbacks, so the emergence of bone tissue engineering brings new hope. Bone tissue engineering is an interdisciplinary biomedical engineering method that involves scaffold materials, seed cells, an...
Citations
... For instance, recent developments in 3D bioprinting have utilized various biomaterials to create scaffolds that support vascularization and robust cell growth [73][74][75]. The incorporation of bioactive ceramics and advanced bioprinting technologies, such as core/shell bioprinting, has led to the fabrication of hybrid scaffolds that offer enhanced mechanical properties and biological functionality [76]. Table 2 summarizes recent studies that demonstrate the capabilities and advancements of 3D printing techniques in scaffold fabrication. ...
... For example, combining 3D printing with electrospinning has enabled the creation of composite scaffolds that not only meet the mechanical and structural requirements of the native bone but also support enhanced vascularization, essential for the healing of complex bone defects [76]. Electrospinning has also been utilized in conjunction with 3D printing to produce fibrous scaffolds, such as those made from silica, using materials such as tetraethyl orthosilicate (TEOS) and polyvinyl alcohol (PVA). ...
In exploring the challenges of bone repair and regeneration, this review evaluates the potential of bone tissue engineering (BTE) as a viable alternative to traditional methods, such as autografts and allografts. Key developments in biomaterials and scaffold fabrication techniques, such as additive manufacturing and cell and bioactive molecule-laden scaffolds, are discussed, along with the integration of bio-responsive scaffolds, which can respond to physical and chemical stimuli. These advancements collectively aim to mimic the natural microenvironment of bone, thereby enhancing osteogenesis and facilitating the formation of new tissue. Through a comprehensive combination of in vitro and in vivo studies, we scrutinize the biocompatibility, osteoinductivity, and osteoconductivity of these engineered scaffolds, as well as their interactions with critical cellular players in bone healing processes. Findings from scaffold fabrication techniques and bio-responsive scaffolds indicate that incorporating nanostructured materials and bioactive compounds is particularly effective in promoting the recruitment and differentiation of osteoprogenitor cells. The therapeutic potential of these advanced biomaterials in clinical settings is widely recognized and the paper advocates continued research into multi-responsive scaffold systems.
... The implementation of these techniques involves the use of pins or mesh for fixation, and in many instances, biomaterial granules are applied to fill the voids. 15,16 Bone blocks have a long history of use, and the existing literature contains numerous reports detailing their indications, methods of use and effects. 17,18 These involve the use of various graft types, including autologous, allogeneic, xenogeneic, and synthetic bone substitutes. ...
... The reconstruction of critical-sized loss or defects caused by trauma, tumor excision, osteoarthritis, and other bone-resorption-related diseases or disorders remains a significant challenge [1][2][3][4][5][6][7]. However, three-dimensional biomaterial scaffolds (produced by means of engineering or tissue engineering technologies) have emerged as relatively novel tools used to repair such damaged hard tissues [8][9][10][11]. Biomimetic scaffolds are designed and generated as biomaterial architectures that promote the regeneration of native tissue [12][13][14][15][16]. Hard tissue surgery scaffolds require mechanical stability in order to support the needed geometry of tissue loss or defects and facilitate external loading. Such scaffolds should provide internal microarchitecture to the tissue that is to be regenerated with an internal, interconnected porous network of effective space for the infiltration, growth, and differentiation of bone marrow mesenchymal stem cells, vasculature ingrowth, and new tissue growth, with the aim of ensuring a channel of material exchange with the external environment (delivering oxygen and other nutrients to the cells, in addition to waste removal) [17][18][19][20]. ...
Hard tissues are living mineralized tissues that possess a high degree of hardness and are found in organs such as bones and teeth (enamel, dentin, and cementum) [...]
... Because 3D printing yields structures that morphologically resemble the multiscale architecture of human tissue, it has been recognized as a useful method for creating tissue engineering scaffolds. Bone tissue engineering, utilizing 3D printed scaffolds, has become a promising approach for bone reconstruction and treatment, overcoming the limitations of traditional bone grafts [3]. Unlike subtractive manufacturing techniques, 3D printing, also known as additive manufacturing, solid freeform fabrication, or rapid prototyping, builds objects from 3D model data, usually by adding material layer by layer [29]. ...
Bones are mineralized connective tissues composed of osteoclasts, osteoblasts, and osteocytes. While bone is one of the few tissues that can regenerate in adulthood, its regeneration is limited in the case of large bone defects due to an environment that is detrimental to bone formation, which can be caused by soft tissue injury and impeded vascularization, ultimately reducing the potential for significant bone creation. Consequently, recent research has focused on tissue engineering and regenerative medicine to address these complex issues. This article reviews recent major advances in the cell components used for bone regeneration studies, specific markers of bone differentiation, 3-dimensional (3D) printing techniques for the structural mimicry of bones, and the use of natural and synthetic biomaterials. Functional bone structures and bone organoids can be created using 3D printing, which allows the reconstruction of bone tissue by attaching living cells to scaffolds. These scaffolds are designed with appropriate shapes and mechanical properties to mimic the bone microenvironment. The application of 3D printing in the development of bone organoids holds promise for providing improved solutions for the development of test systems for disease modeling and drug development.
... 2,11,12 The recent advancements in 3D printing provide suitable alternatives to autologous bone grafts. [13][14][15][16] 3D printed scaffolds can meticulously mimic the microarchitecture and the anatomical structure of bone acting as osteoconductive supports by ensuring host cell adhesion, proliferation and differentiation. 17,18 Among all, polycaprolactone (PCL) is a synthetic polyester polymer widely exploited for the fabrication of 3D scaffolds for bone tissue engineering, due to its good biocompatibility, its moldability, slow degradation rate, and loadbearing properties. ...
The molecular layer that adsorbs on the biomaterial surface upon contacting body tissues and fluids, termed the conditioning layer (CL), influences cell behavior regulating scaffold integration and resilience in a patient-specific fashion. To predict and improve the clinical outcome of 3D-printed scaffolds, graphene coatings are employed in bone tissue engineering, due to the possibility to functionalize its chemical/physical properties. In this study, we investigated the composition and the influence of the CL on three different graphene oxide-based coatings of 3D-printed polycaprolactone (PCL) implants: graphene oxide (–GO), carboxylated GO (–GO–COOH) and reduced GO (–rGO). The effects of surface features and CL were evaluated in vitro using bone marrow-derived mesenchymal stromal cells (hBM-MSC). Our results showed that the CL formed on negatively charged PCL–GO–COOH and PCL–rGO scaffolds reduced cell adhesion, while simultaneously enhancing cell cluster formation and proliferation by a fivefold increase. The quantification of bone mineralized matrix highlighted that CL on both PCL–GO–COOH and PCL–rGO coatings sustained the osteogenic potential of these two types of GO. The analysis of CL components adsorbed on the scaffolds revealed that the PCL–GO–COOH and PCL–rGO coatings tend to entrap specific patterns of serum proteins (e.g. anti-adhesive and osteogenic modulators) and ions (carbonate and phosphate), suggesting a correlation between these enriched components and the observed biological outcomes of conditioned scaffolds. Lastly, PCL–rGO coatings maintained unique antibacterial properties after in vitro simulated CL formation, representing a suitable promising strategy to improve bone grafting capable of shaping CL formation while preserving the favorable osteoinductive properties of scaffolds.
... Research on the bioprinting of type I collagen has focused on hard tissue applications [17,18] such as the bone, teeth, and spine where the mechanical properties play a key role. Bone regeneration fails once it reaches a critical size defect; thus, 3D printing with collagen inks for hard tissue repair is a growing area of research. ...
... To let the collagen pellet solubilize, it was allowed to sit overnight at room temperature. The collagen/acetic acid solution was then placed in a 15 mL, 10 kDa molecular weight cutoff dialysis cassette (Thermo Scientific, Bannockburn, IL, USA) and immersed in ethylenediaminetetraacetic acid (35 mM, EDTA, Fisher Chemical, Lenexa, KS, USA)/H 2 O solution with a pH of 7.5 using sodium hydroxide (10 N, NaOH, Ricca Chemical Co., Arlington, TX, USA) [17]. The pH of the EDTA solution was monitored and maintained at 7.5 daily until the pH no longer fluctuated from 7.5. ...
Three-dimensional printing provides more versatility in the fabrication of scaffold materials for hard and soft tissue replacement, but a critical component is the ink. The ink solution should be biocompatible, stable, and able to maintain scaffold shape, size, and function once printed. This paper describes the development of a collagen ink that remains in a liquid pre-fibrillized state prior to printing. The liquid stability occurs due to the incorporation of ethylenediaminetetraacetic acid (EDTA) during dialysis of the collagen. Collagen inks were 3D-printed using two different printers. The resulting scaffolds were further processed using two different chemical crosslinkers, 1-Ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride)/N-hydroxysuccinimide (EDC/NHS) and genipin; gold nanoparticles were conjugated to the scaffolds. The 3D-printed scaffolds were characterized to determine their extrudability, stability, amount of AuNP conjugated, and overall biocompatibility via cell culture studies using fibroblast cells and stroma cells. The results demonstrated that the liquid collagen ink was amendable to 3D printing and was able to maintain its 3D shape. The scaffolds could be conjugated with gold nanoparticles and demonstrated enhanced biocompatibility. It was concluded that the liquid collagen ink is a good candidate material for the 3D printing of tissue scaffolds.
... This bioprinted structure can be designed to have optimal porosity and permeability, facilitating nutrient and oxygen diffusion throughout the scaffold. 52,53 Moreover, incorporating bioresorbable b-TCP ensures that the scaffold gradually degrades over time, allowing for the natural integration of newly formed bone tissue. This property aligns for future usage with the principles of guided tissue regeneration and guided bone regeneration. ...
Background/purpose
3D-printed bone tissue engineering is becoming recognized as a key approach in dentistry for creating customized bone regeneration treatments fitting patients bone defects requirements. 3D bioprinting offers an innovative method to fabricate detailed 3D structures, closely emulating the native bone micro-environment and better bone regeneration. This study aimed to develop an 3D-bioprintable scaffold using a combination of alginate and β-tricalcium phosphate (β-TCP) with the Cellink® BioX printer, aiming to advance the field of tissue engineering.
Materials and methods
The physical and biological properties of the resulting 3D-printed scaffolds were evaluated at 10 %, 12 %, and 15 % alginate combined with 10 % β-TCP. The scaffolds were characterized through printability, swelling behavior, degradability, and element analysis. The biological assessment included cell viability, alkaline phosphatase (ALP) activity.
Results
10 % alginate/β-TCP 3D printed at 25 °C scaffold demonstrated the optimal condition for printability, swelling capability, and degradability of cell growth and nutrient diffusion. Addition of β-TCP particles significantly improved the 3D printed material viscosity over only alginate (P < 0.05). 10 % alginate/β-TCP enhanced MG-63 cell's proliferation (P < 0.05) and alkaline phosphatase activity (P < 0.001).
Conclusion
This study demonstrated in vitro that 10 % alginate/β-TCP bioink characteristic for fabricating 3D acellular bioprinted scaffolds was the best approach. 10 % alginate/β-TCP bioink 3D-printed scaffold exhibited superior physical properties and promoted enhanced cell viability and alkaline phosphatase activity, showing great potential for personalized bone regeneration treatments.
... In order to promote in vitro bone formation, tissue engineering techniques combine cells, biomaterial scaffolds, and specialized culture conditions that include biochemical and physical stimuli. The creation of biomaterials that are responsive to the changing mechanical and physiological conditions present in vivo is still a significant challenge in bone tissue engineering, one that must be overcome to provide successful long-term repair and favorable clinical results [2,3]. To date, relatively few orthopedic biomaterials with biomimetic and bioresponsive properties have been developed into clinical solutions, despite significant advancements in our understanding of the biological and physicomechanical properties of organs and tissues [4]. ...
This review explores recent advances and challenges in tissue engineering for neural, bone, muscle, and tendon/ligament regeneration. Key topics include Schwann cell-assisted nerve regeneration, nano-fiber scaffolds for bone reconstruction, electrical stimulation in muscle regeneration, and collagen-based scaffolds for tendon/ligament reconstruction. Novel approaches, such as the integration of nanostructured materials and the utilization of growth factors, offer promising avenues for enhancing bone regeneration and overcoming the limitations of traditional grafting methods. Polymeric materials, both natural and synthetic, play significant roles in tissue engineering scaffolds. Natural polymers offer biologically active properties, while synthetic polymers provide controlled degradation and mechanical stability. Combining these materials enhances scaffold properties, fostering tissue regeneration in diverse anatomical contexts. Various polymer combinations in engineering scaffolds for tissue regeneration, including ceramics and composites, are developed with biomimicry, enhancing cell growth and tissue regeneration through techniques like salt leaching and 3D printing, aiming for simpler fabrication and optimized performance for widespread use in tissue engineering. The article underscores the importance of bridging the gap between theory and practical outcomes in tissue engineering research.
... Thanks to the growing technological progress in this field, it will likely reach a level of clinical functionality that will allow for overcoming the limited availability of tissues from human donors, also eliminating the problem due to the possible transmission of infectious diseases [94]. Mechanical properties Low [99,104] Moderate [103] Low [99,104] Moderate [103] Low [99,104] Moderate [103] Low [100] Low [100,101] Moderate [103] Very good [99] Very good [99] Very good [99] Scaffold dimension cm [99] cm [99] cm [99] cm [99] Wide range k cm [99] cm [99] cm [99] Cost Low [95,97,98,104] 5000 $ [99] >Thermal [99] Low [95,98] Mechanical or thermal stress at cellular level [98,100] Require long post-printing treatments [104] Risk of cellular damage due to UV rays or photo-initiators [99] Risk of cellular damage due to UV rays or photo-initiators [99]; High density require a lot of software changes [102] A bioprinted cornea has to meet severe geometrical, biological, optical, and mechanical requirements [106]. Thus, the choice for an adequate bioink is critical: It is quite difficult, but fundamental, to find a biomaterial possessing excellent optical transparency, sufficient mechanical resistance, and, at the same time, good biological compatibility and integrability. ...
... Risks and drawbacksNozzle obstruction; cellular damage at 15-25 kHz[97]; limited pore size and dissolution if organic solvents are used[100]; thermal technology possibly oncogenic[99] ...
The inner structures of the eye are protected by the cornea, which is a transparent membrane exposed to the external environment and subjected to the risk of lesions and diseases, sometimes resulting in impaired vision and blindness. Several eye pathologies can be treated with a keratoplasty, a surgical procedure aimed at replacing the cornea with tissues from human donors. Even though the success rate is high (up to 90% for the first graft in low-risk patients at 5-year follow-up), this approach is limited by the insufficient number of donors and several clinically relevant drawbacks. Alternatively, keratoprosthesis can be applied in an attempt to restore minimal functions of the cornea: For this reason, it is used only for high-risk patients. Recently, many biomaterials of both natural and synthetic origin have been developed as corneal substitutes to restore and replace diseased or injured corneas in low-risk patients. After illustrating the traditional clinical approaches, the present paper aims to review the most innovative solutions that have been recently proposed to regenerate the cornea, avoiding the use of donor tissues. Finally, innovative approaches to biological tissue 3D printing and xenotransplantation will be mentioned.
... Currently, scientists are conducting research on 4D-printed biomaterials in a few applications. This includes the production of functional meniscal implants [82], regeneration of cartilage with chitosan derivatives [83], bone replacement implants for treating losses caused by trauma or genetic diseases [84][85][86][87], and tooth implants [88]. Additionally, there is evidence of the potential usage of 4D-printed biomaterials in the engineering of the cardiovascular system. ...
Biomimetic scaffolds imitate native tissue and can take a multidimensional form. They are biocompatible and can influence cellular metabolism, making them attractive bioengineering platforms. The use of biomimetic scaffolds adds complexity to traditional cell cultivation methods. The most commonly used technique involves cultivating cells on a flat surface in a two-dimensional format due to its simplicity. A three-dimensional (3D) format can provide a microenvironment for surrounding cells. There are two main techniques for obtaining 3D structures based on the presence of scaffolding. Scaffold-free techniques consist of spheroid technologies. Meanwhile, scaffold techniques contain organoids and all constructs that use various types of scaffolds, ranging from decellularized extracellular matrix (dECM) through hydrogels that are one of the most extensively studied forms of potential scaffolds for 3D culture up to 4D bioprinted biomaterials. 3D bioprinting is one of the most important techniques used to create biomimetic scaffolds. The versatility of this technique allows the use of many different types of inks, mainly hydrogels, as well as cells and inorganic substances. Increasing amounts of data provide evidence of vast potential of biomimetic scaffolds usage in tissue engineering and personalized medicine, with the main area of potential application being the regeneration of skin and musculoskeletal systems. Recent papers also indicate increasing amounts of in vivo tests of products based on biomimetic scaffolds, which further strengthen the importance of this branch of tissue engineering and emphasize the need for extensive research to provide safe for humansbiomimetic tissues and organs. In this review article, we provide a review of the recent advancements in the field of biomimetic scaffolds preceded by an overview of cell culture technologies that led to the development of biomimetic scaffold techniques as the most complex type of cell culture.
