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.

Strategies for the Codelivery of Osteoclasts and Mesenchymal Stem Cells in 3D-Printable Osteochondral Scaffolds.

Osteochondral defects, characterized by structural compromises to articular cartilage and subchondral bone, can cause pain and lead to progressive cartilage damage and eventual osteoarthritis. Unfortunately, repairing these defects remains difficult because of the poor regenerative properties of cartilage and complex mechanical demands of the joint. As such, the field of tissue engineering aims to develop multiphasic implants that replace pathological cartilage and bone tissue and restore mechanical functionality to the joint. Recent bone physiology investigations have demonstrated that osteoclast (OC) lineage cells are inextricably involved in osteoblastic bone formation through an extensive network of anabolic signaling pathways, and so the codelivery OC and osteoblast (OB) lineage cells within scaffolds is being actively explored for bone tissue engineering purposes. However, it remains unclear how these cells can be incorporated into the design of multiphasic osteochondral scaffolds to potentially enhance subchondral bone formation and subsequent implant osseointegration. To explore this question, we examined direct surface seeding and hydrogel encapsulation as potential scaffold cellularization strategies. First, we examined how OC precursor cells and peripheral blood monocytes (PBMCs) influence early-stage bone matrix development and osteogenesis in 2D coculture. Then, we evaluated the osteogenic potential of mesenchymal stem cells (MSCs) and PBMCs cocultures encapsulated within a gelatin methacrylate (GelMA) hydrogel system. Our findings demonstrate that coculturing PBMCs with MSCs in 2D cultures significantly enhanced cell proliferation, early bone matrix deposition, and the formation of cell clusters by Day 28. However, we observed no significant difference in type I collagen deposition between GelMA hydrogel scaffolds cultured in basal and OC conditions during the same period. In addition, we found that the GelMA hydrogel system with MSC/PBMC cocultures in OC conditions exhibited decreased osteogenic activity by Day 28. Collectively, our findings support the osteogenic potential of OC-lineage cells in 2D culture conditions, and the potential benefits of surface-seeding for the codelivery of OC-lineage cells and MSCs in osteo-scaffolds for enhanced osteochondral regeneration and broader bone tissue engineering purposes.

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.

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.

Functionalized carbon-based nanomaterials and quantum dots with antibacterial activity: a review.

INTRODUCTION: Emergence of antibiotic resistance in bacteria is a complicated issue, especially when treating infectious immunodeficiency related diseases. In recent years, when compared to bulk materials, nanomaterials (NMs) with specific antibacterial activities have played a novel role in treating bacterial infections. Among NMs, quantum dots (QDs), specifically carbon containing QDs including graphene oxide QD (GOQD), graphene QD (GQD), and carbon QD (CQD), have demonstrated bacteriostatic and bactericidal activities via photodynamic (PD) effects against antibiotic resistant bacteria under a certain wavelength of light. AREA COVERED: In this mini-review, recent advances and challenges related to antibacterial and biocompatibility activities of modified GQD, GOQD, CQD, and carbon nanotubes (CNTs) are discussed. EXPERT OPINION: Lower stability and biocompatibility of QDs at higher doses in physiological conditions are major disadvantages. In this regard, functionalization of these QDs can result in appropriate bactericidal, biocompatibility, and biodegradability properties. In the case of CNTs including single-wall carbon nanotube (SWCNTs) and multiwall carbon nanotube (MWCNTs), aspect ratio (AR) is a determinant factor for the antibacterial value. Moreover, MWCNTs show a lower antibacterial ability compared to SWCNTs, which can be improved by modifying their surface.