Additive manufacturing of Bio-inspired ceramic bone Scaffolds: Structural Design, mechanical properties and biocompatibility

In the literature there are conflicting reports on the optimal scaffold mean pore size required for successful bone tissue engineering. This study set out to investigate the effect of mean pore size, in a series of collagen-glycosaminoglycan (CG) scaffolds with mean pore sizes ranging from 85 microm to 325 microm, on osteoblast adhesion and early stage proliferation up to 7 days post-seeding. The results show that cell number was highest in scaffolds with the largest pore size of 325 microm. However, an early additional peak in cell number was also seen in scaffolds with a mean pore size of 120 microm at time points up to 48 h post-seeding. This is consistent with previous studies from our laboratory which suggest that scaffold specific surface area plays an important role on initial cell adhesion. This early peak disappears following cell proliferation indicating that while specific surface area may be important for initial cell adhesion, improved cell migration provided by scaffolds with pores above 300 microm overcomes this effect. An added advantage of the larger pores is a reduction in cell aggregations that develop along the edges of the scaffolds. Ultimately scaffolds with a mean pore size of 325 microm were deemed optimal for bone tissue engineering.

Critical-sized bone defect repair remains a substantial challenge in clinical settings and requires bone grafts or bone substitute materials. However, existing biomaterials often do not meet the clinical requirements of structural support, osteoinductive property, and controllable biodegradability. To treat large-scale bone defects, the development of three-dimensional (3D) porous scaffolds has received considerable focus within bone engineering. A variety of biomaterials and manufacturing methods, including 3D printing, have emerged to fabricate patient-specific bioactive scaffolds that possess controlled micro-architectures for bridging bone defects in complex configurations. During the last decade, with the development of the 3D printing industry, a large number of tissue-engineered scaffolds have been created for preclinical and clinical applications using novel materials and innovative technologies. Thus, this review provides a brief overview of current progress in existing biomaterials and tissue engineering scaffolds prepared by 3D printing technologies, with an emphasis on the material selection, scaffold design optimization, and their preclinical and clinical applications in the repair of critical-sized bone defects. Furthermore, it will elaborate on the current limitations and potential future prospects of 3D printing technology. STATEMENT OF SIGNIFICANCE: 3D printing has emerged as a critical fabrication process for bone engineering due to its ability to control bulk geometry and internal structure of tissue scaffolds. The advancement of bioprinting methods and compatible ink materials for bone engineering have been a major focus to develop optimal 3D scaffolds for bone defect repair. Achieving a successful balance of cellular function, cellular viability, and mechanical integrity under load-bearing conditions is critical. Hybridization of natural and synthetic polymer-based materials is a promising approach to create novel tissue engineered scaffolds that combines the advantages of both materials and meets various requirements, including biological activity, mechanical strength, easy fabrication and controllable degradation. 3D printing is linked to the future of bone grafts to create on-demand patient-specific scaffolds.

Toward the aim of personalized treatment, three-dimensional (3D) printing technology has been widely used in bone tissue engineering owing to its advantage of a fast, precise, and controllable fabrication process. Conventional bioceramic scaffolds are mainly used for bone tissue engineering; however, there has been a significant change in the application of bioceramic scaffolds during the past several years. Therefore, this review focuses on 3D-printed bioceramic scaffolds with different compositions and hierarchical structures (macro, micro, and nano scales), and their effects on the mechanical, degradation, permeability, and biological properties. Further, this review highlights 3D-printed bioceramic scaffolds for applications extending from bone tissue regeneration to bone tumor therapy. This review emphasizes recent developments in functional 3D-printed bioceramic scaffolds with the ability to be used for both tumor therapy and bone tissue regeneration. Considering the challenges in bone tumor therapy, these functional bioceramic scaffolds have a great potential in repairing bone defects induced by surgery and kill the possibly residual tumor cells to achieve bone tumor therapy. Finally, a brief perspective regarding future directions in this field was also provided. The review not only gives a summary of the research developments in bioceramic science but also offers a new therapy strategy by extending multifunctions of traditional biomaterials toward a specific disease.