An Exploration of the Role of Osteoclast Lineage Cells in Bone Tissue Engineering.

Bone defects because of age, trauma, and surgery, which are exacerbated by medication side effects and common diseases such as osteoporosis, diabetes, and rheumatoid arthritis, are a problem of epidemic scale. The present clinical standard for treating these defects includes autografts and allografts. Although both treatments can promote robust regenerative outcomes, they fail to strike a desirable balance of availability, side effect profile, consistent regenerative efficacy, and affordability. This difficulty has contributed to the rise of bone tissue engineering (BTE) as a potential avenue through which enhanced bone regeneration could be delivered. BTE is founded upon a paradigm of using biomaterials, bioactive factors, osteoblast lineage cells (ObLCs), and vascularization to cue deficient bone tissue into a state of regeneration. Despite promising preclinical results, BTE has had modest success in being translated into the clinical setting. One barrier has been the simplicity of its paradigm relative to the complexity of biological bone. Therefore, this paradigm must be critically examined and expanded to better account for this complexity. One potential avenue for this is a more detailed consideration of osteoclast lineage cells (OcLCs). Although these cells ostensibly oppose ObLCs and bone regeneration through their resorptive functions, a myriad of investigations have shed light on their potential to influence bone equilibrium in more complex ways through their interactions with both ObLCs and bone matrix. Most BTE research has not systematically evaluated their influence. Yet contrary to expectations associated with the paradigm, a selection of BTE investigations has demonstrated that this influence can enhance bone regeneration in certain contexts. In addition, much work has elucidated the role of many controllable scaffold parameters in both inhibiting and stimulating the activity of OcLCs in parallel to bone regeneration. Therefore, this review aims to detail and explore the implications of OcLCs in BTE and how they can be leveraged to improve upon the existing BTE paradigm.

Designing Biomimetic 3D-Printed Osteochondral Scaffolds for Enhanced Load-Bearing Capacity.

Osteoarthritis is a debilitating chronic joint disorder that affects millions of people worldwide. Since palliative and surgical treatments cannot completely regenerate hyaline cartilage within the articulating joint, osteochondral (OC) tissue engineering has been explored to heal OC defects. Utilizing computational simulations and three-dimensional (3D) printing, we aimed to build rationale around fabricating OC scaffolds with enhanced biomechanics. First, computational simulations revealed that interfacial fibrils within a bilayer alter OC scaffold deformation patterns by redirecting load-induced stresses toward the top of the cartilage layer. Principal component analysis revealed that scaffolds with 800 µm long fibrils (scaffolds 8A-8H) possessed optimal biomechanical properties to withstand compression and shear forces. While compression testing indicated that OC scaffolds with 800 µm fibrils did not have greater compressive moduli than other scaffolds, interfacial shear tests indicated that scaffold 8H possessed the greatest shear strength. Lastly, failure analysis demonstrated that yielding or buckling models describe interfacial fibril failure depending on fibril slenderness S. Specifically for scaffolds with packing density n = 6 and n = 8, the yielding failure model fits experimental loads with S < 10, while the buckling model fitted scaffolds with S < 10 slenderness. The research presented provides critical insights into designing 3D printed interfacial scaffolds with refined biomechanics toward improving OC tissue engineering outcomes.

Biomechanical Aspects of Osteochondral Regeneration: Implications and Strategies for Three-Dimensional Bioprinting.

Osteoarthritis is among the most prevalent of musculoskeletal disorders in the world that causes joint pain, deformity, and limited range of movement. The resulting osteochondral defect can significantly decrease the patient's quality of life, but current treatment options have not demonstrated the capacity to fully regenerate the entire osteochondral microenvironment. Structurally, the osteochondral unit is a composite system composed of three layers-articular cartilage, calcified cartilage, and subchondral bone. Collectively these distinct layers contribute to the distinct biomechanical properties that maintain the health and aid in load transfer during joint articulation. The purpose of this review was to examine the role of the osteochondral interface in tissue engineering. Topics of discussion include the biomechanics of the osteochondral unit and an overview of various strategies for osteochondral interface tissue engineering, with a specific focus on three-dimensional bioprinting. The goal of this review was to elucidate the importance of the osteochondral interface and overview some strategies of developing an interface layer within tissue engineered scaffolds. Impact Statement This review provides an overview of interface tissue engineering for osteochondral regeneration. It offers a detailed investigation into the biomechanics of the osteochondral unit as it relates to tissue engineering, and highlights the strategies that have been utilized to develop the osteochondral interface within tissue engineering scaffolds.

Computational investigation of interface printing patterns within 3D printed multilayered scaffolds for osteochondral tissue engineering.

Osteoarthritis is a highly prevalent rheumatic musculoskeletal disorder that commonly affects many joints. Repetitive joint overloading perpetuates the damage to the affected cartilage, which undermines the structural integrity of the osteochondral unit. Various tissue engineering strategies have been employed to design multiphasic osteochondral scaffolds that recapitulate layer-specific biomechanical properties, but the inability to fully satisfy mechanical demands within the joint has limited their success. Through computational modeling and extrusion-based bioprinting, we attempted to fabricate a biphasic osteochondral scaffold with improved shear properties and a mechanically strong interface. A 3D stationary solid mechanics model was developed to simulate the effect of lateral shear force on various thermoplastic polymer/hydrogel scaffolds with a patterned interface. Additionally, interfacial shear tests were performed on bioprinted polycaprolactone (PCL)/hydrogel interface scaffolds. The first simulation showed that the PCL/gelatin methacrylate (GelMA) and PCL/polyethylene glycol diacrylate (PEGDA) scaffolds interlocking hydrogel and PCL at interface in a 1:1 ratio possessed the largest average tensile (PCL/GelMA: 80.52 kPa; PCL/PEGDA: 79.75 kPa) and compressive stress (PCL/GelMA: 74.71 kPa; PCL/PEGDA: 73.83 kPa). Although there were significant differences in shear strength between PCL/GelMA and PCL/PEGDA scaffolds, no significant difference was observed among the treatment groups within both scaffold types. Lastly, the hypothetical simulations of potential biphasic 3D printed scaffolds showed that for every order of magnitude decrease in Young's modulus (E) of the soft bioink, all the scaffolds underwent an exponential increase in average displacement at the cartilage and interface layers. The following work provides valuable insights into the biomechanics of 3D printed osteochondral scaffolds, which will help inform future scaffold designs for enhanced regenerative outcomes.