Abstract:Jawbone differs from other bones in many aspects, including its developmental origin and the occurrence of jawbone-specific diseases like MRONJ (medication-related osteonecrosis of the jaw). Although there is a strong need, adequate in vitro models of this unique environment are sparse to date. While previous approaches are reliant e.g. on scaffolds or spheroid culture, 3D bioprinting enables free-form fabrication of complex living tissue structures. In the present work, production of human jawbone models was … Show more
“…Simply implanting materials or inoculating cells on the surface of materials before transplantation, it is difficult to make cells grow into materials. Unlike that, 3D bioprinting generates customized macroporous implants for biomaterials and cells to simulate a 3D growth environment and make cells orientated and evenly distributed in scaffolds [ 33 ]. In our scaffolds, PCL and GelMA have high biocompatibility, and PCL has been approved for clinical use by FDA [ 34 , 35 ].…”
Growth factors were often used to improve the bioactivity of biomaterials in order to fabricate biofunctionalized bone grafts for bone defect repair. However, supraphysiological concentrations of growth factors for improving bioactivity could lead to serious side effects, such as ectopic bone formation, radiculitis, swelling of soft tissue in the neck, etc. Therefore, safely and effectively applying growth factors in bone repair biomaterials comes to be an urgent problem that needs to be addressed. In this study, an appropriate concentration (50 ng/mL) of Wnt3a was used to pretreat the 3D-bioprinting gelatin methacryloyl(GelMA)/polycaprolactone(PCL) scaffold loaded with bone marrow stromal cell line ST2 for 24 h. This pretreatment promoted the cell proliferation, osteogenic differentiation, and mineralization of ST2 in the scaffold in vitro, and enhanced angiogenesis and osteogenesis after being implanted in critical-sized mouse calvarial defects. On the contrary, the inhibition of Wnt/β-catenin signaling in ST2 cells reduced the bone repair effect of this scaffold. These results suggested that ST2/GelMA/PCL scaffolds pretreated with an appropriate concentration of Wnt3a in culture medium could effectively enhance the osteogenic and angiogenic activity of bone repair biomaterials both in vitro and in vivo. Moreover, it would avoid the side effects caused by the supraphysiological concentrations of growth factors. This functionalized scaffold with osteogenic and angiogenic activity might be used as an outstanding bone substitute for bone regeneration and repair.
“…Simply implanting materials or inoculating cells on the surface of materials before transplantation, it is difficult to make cells grow into materials. Unlike that, 3D bioprinting generates customized macroporous implants for biomaterials and cells to simulate a 3D growth environment and make cells orientated and evenly distributed in scaffolds [ 33 ]. In our scaffolds, PCL and GelMA have high biocompatibility, and PCL has been approved for clinical use by FDA [ 34 , 35 ].…”
Growth factors were often used to improve the bioactivity of biomaterials in order to fabricate biofunctionalized bone grafts for bone defect repair. However, supraphysiological concentrations of growth factors for improving bioactivity could lead to serious side effects, such as ectopic bone formation, radiculitis, swelling of soft tissue in the neck, etc. Therefore, safely and effectively applying growth factors in bone repair biomaterials comes to be an urgent problem that needs to be addressed. In this study, an appropriate concentration (50 ng/mL) of Wnt3a was used to pretreat the 3D-bioprinting gelatin methacryloyl(GelMA)/polycaprolactone(PCL) scaffold loaded with bone marrow stromal cell line ST2 for 24 h. This pretreatment promoted the cell proliferation, osteogenic differentiation, and mineralization of ST2 in the scaffold in vitro, and enhanced angiogenesis and osteogenesis after being implanted in critical-sized mouse calvarial defects. On the contrary, the inhibition of Wnt/β-catenin signaling in ST2 cells reduced the bone repair effect of this scaffold. These results suggested that ST2/GelMA/PCL scaffolds pretreated with an appropriate concentration of Wnt3a in culture medium could effectively enhance the osteogenic and angiogenic activity of bone repair biomaterials both in vitro and in vivo. Moreover, it would avoid the side effects caused by the supraphysiological concentrations of growth factors. This functionalized scaffold with osteogenic and angiogenic activity might be used as an outstanding bone substitute for bone regeneration and repair.
“…For these reasons, solving the low-resolution problem is an urgent issue in bone bioprinting. 38 , 39 Fig. 2 Measurement and correction trajectory of a bone scaffold.…”
Bioprinting is an emerging additive manufacturing technology that has enormous potential in bone implantation and repair. The insufficient accuracy of the shape of bioprinted parts is a primary clinical barrier that prevents widespread utilization of bioprinting, especially for bone design with high-resolution requirements. During the last five years, the use of computer vision for process control has been widely practiced in the manufacturing field. Computer vision can improve the performance of bioprinting for bone research with respect to various aspects, including accuracy, resolution, and cell survival rate. Hence, computer vision plays a substantial role in addressing the current defect problem in bioprinting for bone research. In this review, recent advances in the application of computer vision in bioprinting for bone research are summarized and categorized into three groups based on different defect types: bone scaffold process control, deep learning, and cell viability models. The collection of printing parameters, data processing, and feedback of bioprinting information, which ultimately improves printing capabilities, are further discussed. We envision that computer vision may offer opportunities to accelerate bioprinting development and provide a new perception for bone research.
“…Collagen, and its irreversibly hydrolyzed form gelatin, is a water-soluble protein often derived from porcine or bovine sources, but has recently gained interest by being sourced from other animals including fish [ 125 ]. Several examples have highlighted the potential of both collagen and gelatin-based bioinks [ 39 , 45 , 46 , 49 , 109 , 124 , 126 , 127 , 128 ], most commonly combined with extrusion-based technologies due to their thermoresponsive properties [ 124 , 129 ]. Although both collagen- and gelatin-based medical devices have long since been used within clinics to repair damaged tissues [ 124 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 ], it is still far from the standard musculoskeletal repair practice, as it is not consistently successful.…”
Biofabrication has emerged as an attractive strategy to personalise medical care and provide new treatments for common organ damage or diseases. While it has made impactful headway in e.g., skin grafting, drug testing and cancer research purposes, its application to treat musculoskeletal tissue disorders in a clinical setting remains scarce. Albeit with several in vitro breakthroughs over the past decade, standard musculoskeletal treatments are still limited to palliative care or surgical interventions with limited long-term effects and biological functionality. To better understand this lack of translation, it is important to study connections between basic science challenges and developments with translational hurdles and evolving frameworks for this fully disruptive technology that is biofabrication. This review paper thus looks closely at the processing stage of biofabrication, specifically at the bioinks suitable for musculoskeletal tissue fabrication and their trends of usage. This includes underlying composite bioink strategies to address the shortfalls of sole biomaterials. We also review recent advances made to overcome long-standing challenges in the field of biofabrication, namely bioprinting of low-viscosity bioinks, controlled delivery of growth factors, and the fabrication of spatially graded biological and structural scaffolds to help biofabricate more clinically relevant constructs. We further explore the clinical application of biofabricated musculoskeletal structures, regulatory pathways, and challenges for clinical translation, while identifying the opportunities that currently lie closest to clinical translation. In this article, we consider the next era of biofabrication and the overarching challenges that need to be addressed to reach clinical relevance.
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