Mimetic Hierarchical Approaches for Osteochondral Tissue Engineering

Abstract

In order to engineer biomimetic osteochondral (OC) construct, it is necessary to address both the cartilage and bone phase of the construct, as well as the interface between them, in effect mimicking the developmental processes when generating hierarchical scaffolds that show gradual changes of physical and mechanical properties, ideally complemented with the biochemical gradients. There are several components whose characteristics need to be taken into account in such biomimetic approach, including cells, scaffolds, bioreactors as well as various developmental processes such as mesenchymal condensation and vascularization, that need to be stimulated through the use of growth factors, mechanical stimulation, purinergic signaling, low oxygen conditioning, and immunomodulation. This chapter gives overview of these biomimetic OC system components, including the OC interface, as well as various methods of fabrication utilized in OC biomimetic tissue engineering (TE) of gradient scaffolds. Special attention is given to addressing the issue of achieving clinical size, anatomically shaped constructs. Besides such neotissue engineering for potential clinical use, other applications of biomimetic OC TE including formation of the OC tissues to be used as high-fidelity disease/ healing models and as in vitro models for drug toxicity/efficacy evaluation are covered. Highlights Biomimetic OC TE uses "smart" scaffolds able to locally regulate cell phenotypes and dual-flow bioreactors for two sets of conditions for cartilage/ bone Protocols for hierarchical OC grafts engineering should entail mesenchymal condensation for cartilage and vascular component for bone Immunomodulation, low oxygen tension, purinergic signaling, time dependence of stimuli application are important aspects to consider in biomimetic OC TE Mimetic Hierarchical Approaches for Osteochondral Tissue Engineering Ivana GadjanskiAbstract In order to engineer biomimetic osteochondral (OC) construct, it is necessary to address both the cartilage and bone phase of the construct, as well as the interface between them, in effect mimicking the developmental processes when generating hierarchical scaffolds that show gradual changes of physical and mechanical properties, ideally complemented with the biochemical gradients. There are several components whose characteristics need to be taken into account in such biomimetic approach, including cells, scaffolds, bioreactors as well as various developmental processes such as mesenchymal condensation and vascularization, that need to be stimulated through the use of growth factors, mechanical stimulation, purinergic signaling, low oxygen conditioning, and immunomodulation. This chapter gives overview of these biomimetic OC system components, including the OC interface, as well as various methods of fabrication utilized in OC biomimetic tissue engineering (TE) of gradient scaffolds. Special attention is given to addressing the issue of achieving clinical size, anatomically shaped constructs. Besides such neotissue en...

Natural and Synthetic Bioinks for 3D Bioprinting

“…Collagen type I is one of the most important organic constituents of extracellular matrix (ECM) in mammalian cells. [ 8,45,46 ] Collagen type I hydrogels show excellent biocompatibility and have been widely utilized in biomedical applications. [ 37,47–50 ] Osidak et al [ 51 ] used Viscoll containing varying concentrations of collagen type I as bioink for direct printing using an extrusion‐based bioprinting technique to form scaffolds ( Figure 6 ).…”

The Application of Bioreactors for Cartilage Tissue Engineering: Advances, Limitations, and Future Perspectives

“…Moreover, with the development of TEAC, some novel bioreactors that provide noncontact biomechanical loads have been designed, such as magnetic bioreactors and ultrasonic bioreactors. The application of these bioreactors (as shown in Table 1 ) aims to simulate the complex physiological and biomechanical environments in AC [ 3 ].…”

“…The regeneration of articular cartilage (AC) is one of the challenges in regenerative medicine due to its poor regenerative capacity [ 1 , 2 ]. Natural AC is a complex hierarchical structure that is avascular with four layers: the surface zone, middle zone, deep zone, and calcified zone [ 3 ]. These zones have different biochemical compositions, chondrocyte phenotypes, and physiological characteristics tied directly to the effects of mechanical loading and the physiological environment [ 4 , 5 ].…”

“…The environment includes hydrostatic pressure; fluid shear force; microgravity; sound waves; magnetic field; and biochemical conditions, such as the pH, CO2, and pO2 levels; temperature; and growth factors. Therefore, traditional cell culture techniques cannot meet the requirements of AC tissue engineering, and complex bioreactors have recently been used to simulate the physical and mechanical environment that influences chondrogenesis [ 3 , 18 , 19 ]. Bioreactors are powerful dynamic culture model systems that can apply a combination of chemical, mechanical, electrical, and/or magnetic stimulation to study the basic mechanisms of cell function under physiologically related conditions within seeded cells and to facilitate the correct development of tissue [ 20 , 21 ].…”

Multimaterial Segmented Fiber Printing for Gradient Tissue Engineering

“…12,13 Recently, several techniques have been used to develop vertical and horizontal gradients that can mimic complex gradients found in native tissues such as osteochondral defects or tendon-tobone insertions. [14][15][16][17] Despite good results for these gradients, the preparation of complex multimaterial scaffolds with precise structures is still immature in development. There is a lack of methodologies to efficiently generate scaffolds with tailored three-dimensional (3D) control over distributions in composition, structure, degradation rate, and morphological and mechanical properties.…”