3D Bioprinted Scaffolds for Bone Tissue Engineering: State-Of-The-Art and Emerging Technologies

Abstract

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 reconstitution and treatment. Bioprinting technology allows for incorporation of living cells and/or growth factors into scaffolds aiming to mimic the structure and properties of the native bone. To date, a wide range of biomaterials (either natural or synthetic polymers), as well as various cells and growth factors, have been explored for use in scaffold bioprinting. However, a key challenge that remains is the fabrication of scaffolds that meet structure, mechanical, and osteoconductive requirements of native bone and support vascularization. In this review, we briefly present the latest developments and discoveries of CSD treatment by means of bioprinted scaffolds, with a focus on the biomaterials, cells, and growth factors for formulating bioinks and their bioprinting techniques. Promising state-of-the-art pathways or strategies recently developed for bioprinting bone scaffolds are highlighted, including the incorporation of bioactive ceramics to create composite scaffolds, the use of advanced bioprinting technologies (e.g., core/shell bioprinting) to form hybrid scaffolds or systems, as well as the rigorous design of scaffolds by taking into account of the influence of such parameters as scaffold pore geometry and porosity. We also review in-vitro assays and in-vivo models to track bone regeneration, followed by a discussion of current limitations associated with 3D bioprinting technologies for BTE. We conclude this review with emerging approaches in this field, including the development of gradient scaffolds, four-dimensional (4D) printing technology via smart materials, organoids, and cell aggregates/spheroids along with future avenues for related BTE.

Poly(ε-caprolactone)-based nanofibrous scaffold incorporated with decellularized bone extracellular matrix as a potential strategy for bone regeneration

“…It has been estimated that there will be about 28 million orthopedic surgery procedures worldwide by 2022, and a critical issue is the demand for bone substitutes will greatly increase, which is the second most transplanted tissue annually now [37] . Due to the drawbacks of immune response, donor site morbidity and shortage of supply, it seems that autografts and allograft will not fully cover the needs of bone transplantation [38,39] .…”

3D-Printing for Critical Sized Bone Defects: Current Concepts and Future Directions

“…A commonly cited concern with thermal inkjet printing is the difficulty with standardizing droplet size, as well as limitations with starting materials due to the low viscosity necessary for proper expulsion of the ink droplet [ 113 , 114 ]. Piezoelectric inkjet printing has the potential to overcome these obstacles, but has not been well studied in bone tissue engineering.…”

“…Extrusion bioprinting, also referred to as direct ink writing (DIW), involves the use of pneumatic air pressure or mechanical systems such as pistons, screws, and valves to continuously disperse multiple different bioinks simultaneously, allowing for fabrication of scaffolds that emulate highly complex tissues ( Figure 5 ) [ 75 , 118 ]. Some disadvantages of this technique include cellular exposure to high mechanical and shearing stresses during the extrusion process, as well as limited resolution of the final construct ( Table 2 ) [ 114 ]. However, multiple studies report high levels of cell viability with cell-laden bioinks, as well as robust osteogenic and chondrogenic differentiation [ 119 , 120 , 121 ].…”

Anti-Inflammatory and Anti-Angiogenic Aattributes of Moringa olifera Lam. and its Nanoclay-Based Pectin-Sericin films

“…An engineered drug delivery system may modify the biopharmaceutical properties of the active pharmaceutical agents (APIs) to achieve an immediate or delayed-release scenario as per therapeutic requirements. Notably, the programmed delivery of oral drugs to deliver medication at the site of action is valuable in chronotherapy of multiple pathologies ( Yazdanpanah et al, 2022 ). Many plant products such as mucilage, gums and exudates are used as excipients in pharmaceutical dosage forms ( Ullah et al, 2020 ).…”