Challenges and Innovations in Osteochondral Regeneration: Insights from Biology and Inputs from Bioengineering toward the Optimization of Tissue Engineering Strategies

Abstract

Due to the extremely high incidence of lesions and diseases in aging population, it is critical to put all efforts into developing a successful implant for osteochondral tissue regeneration. Many of the patients undergoing surgery present osteochondral fissure extending until the subchondral bone (corresponding to a IV grade according to the conventional radiographic classification by Berndt and Harty). Therefore, strategies for functional tissue regeneration should also aim at healing the subchondral bone and joint interface, besides hyaline cartilage. With the ambition of contributing to solving this problem, several research groups have been working intensively on the development of tailored implants that could promote that complex osteochondral regeneration. These implants may be manufactured through a wide variety of processes and use a wide variety of (bio)materials. This review aimed to examine the state of the art regarding the challenges, advantages, and drawbacks of the current strategies for osteochondral regeneration. One of the most promising approaches relies on the principles of additive manufacturing, where technologies are used that allow for the production of complex 3D structures with a high level of control, intended and predefined geometry, size, and interconnected pores, in a reproducible way. However, not all materials are suitable for these processes, and their features should be examined, targeting a successful regeneration.

Directed Regeneration of Osteochondral Tissue by Hierarchical Assembly of Spatially Organized Composite Spheroids

“…Connective tissues migrate rapidly and cover a defect area in osteochondral tissue to block an infection from external factors, and thin compact bones are formed following a pre‐generated fibrous layer. [ 67 ] However, this compact bone formed near the cartilage area often disturbs cartilage regeneration because the highly mineralized bony structure extinguishes chondrogenic cell migration and inhibits chondrocyte differentiation and chondral ossification. [ 67 ] Likewise, regenerated tissues in the Defect group showed CT and an adherent thin compact bone layer (CB) in the cartilage area (Figure 6e ), while the internal subchondral layer remained hollow with tissues rarely formed (Figure 6c,e ).…”

“…[ 67 ] However, this compact bone formed near the cartilage area often disturbs cartilage regeneration because the highly mineralized bony structure extinguishes chondrogenic cell migration and inhibits chondrocyte differentiation and chondral ossification. [ 67 ] Likewise, regenerated tissues in the Defect group showed CT and an adherent thin compact bone layer (CB) in the cartilage area (Figure 6e ), while the internal subchondral layer remained hollow with tissues rarely formed (Figure 6c,e ). In contrast, the structures were not found in the chamber‐implanted groups, which indicated that the chamber slowed the rapid infiltration of fibrous tissues in the cartilage area and secured a space for hard tissue regeneration (Figure 6e–h ).…”

Poly-Alanine-ε-Caprolacton-Methacrylate as Scaffold Material with Tuneable Biomechanical Properties for Osteochondral Implants

“…Ideally, the scaffold should support the defects mechanically until new bone is formed. Natural bone and cartilage are characterized by an anisotropic structure; thus, the scaffold should consist of a hierarchically organised architecture [ 4 , 5 ]. Another important point is that growth factors should be incorporated inside the structure to enhance osteogenesis, chondrogenesis and angiogenesis [ 3 , 5 , 6 ].…”

A Comparison of the Capacity of Mesenchymal Stromal Cells for Cartilage Regeneration Depending on Collagen-Based Injectable Biomimetic Scaffold Type

“…The major problem of healthcare in the industrial community is the damage of joint cartilage, which is associated with the limited capacity of the tissue to regenerate [ 1 ]. The gold standard in cell therapy of cartilage diseases today is the method of autologous chondrocyte implantation which has some disadvantages [ 2 ].…”