Encyclopedia
Osteochondral regeneration, due to the different cartilages and subchondral bone composition, together with biochemical, biomechanical, and biological properties, becomes a big challenge.
- hyaline cartilage
- subchondral bone
- tissue engineering
1. Introduction
In the last years, the world has been witnessing the progressive increase in the prevalence of debilitating disorders affecting osteochondral tissues, leading to the functional impairment of synovial joints and severe pain [1]. In particular, osteoarthritis (OA) represents a significant health burden in developed and developing countries, mostly due to aging and to the increase of risk factors, including obesity and sedentary lifestyle, along with intervening joint injuries [2][3][2,3]. OA is a chronic and etiologically heterogeneous joint disorder, which represents the most prevalent musculoskeletal disorder worldwide. In OA, the progressive degeneration of the hyaline cartilage that lines the surfaces of bones articulating through synovial (i.e., moving) joints causes direct bone-to-bone attrition during movements throughout the body [4][5][4,5].
The joint degenerative process in OA is characterized by an activation of maladaptive repair responses including pro-inflammatory pathways of innate immunity, commonly initiated by micro-and macro-injuries that induce cell stress and extracellular matrix (ECM) degradation [6]. This disease is on the World Health Organization’s top list of concerns, as the breakdown of articular cartilage is a major health matter to which there are few effective solutions, at least with guaranteed success [7]. Direct trauma, chronic degeneration (i.e., mechanical overload), or an abnormality of the underlying subchondral bone are the main detailed factors to produce articular cartilage lesions [8][9][8,9]. OA is typically associated with risk factors that reflect lifestyle attitudes, such as aging, obesity, nutritional deficiencies, and physical (in)activity, along with joint-related co-morbidities, including intervening traumas and/or ischemic injuries, malalignment, and abnormal mechanical load [2], interacting in a complex pathophysiology, and causing over 250 million individuals to be affected worldwide. This prevalence justifies the need to improve and boost research efforts that contribute to the development of novel treatments, leveraging integrated and multidisciplinary approaches.
Overall, the osteochondral tissue is an integrated load-bearing structure that represents a significant challenge in regenerative medicine, owing to its nanostructural complexity, stratified architecture, and crucial biomechanical properties [10][11][12][10,11,12]. Hence, engineering the optimum osteochondral construct has been somewhat hampered due to poor tissue formation and problematic integration at the cartilage-bone interface [13].
2. Tissue Engineering for Osteochondral Regeneration
The regeneration of articular cartilage resulting from degenerative joint disease is an exciting area under investigation using Tissue Engineering (TE) approaches, which have been yielding promising experimental regenerative strategies [14][15][47,48]. TE approaches involve the combination of three main components, i.e., scaffold, biomolecules (e.g., growth factors and bone-inducing agents, drugs, such as antimicrobials, etc.), and cells.
Currently, there are several available strategies for treating a joint cartilage lesion, including some already on the market (palliative; microfraction; grafts; cell-based; whole tissue transplantation; scaffold-based) and others that are still under investigation (cell plus scaffold-based; and hydrogels-based or cell plus hydrogel-based). Accordingly, we might question why OA is a burden for health systems. Most of the existing procedures show significant drawbacks and need to be improved to achieve functional osteochondral regeneration. In this regard, most of the available studies test cartilage regeneration under static conditions.
Not long ago, it was reported that the most commonly used 3D scaffold architectures in cartilage TE were porous 3D sponges [16][49]. This non-conventional procedure does not allow control over the inner architecture, thus not guaranteeing the desired interconnectivity between pores. Embracing technology advancements, TE overcomes some of the mentioned drawbacks, in particular providing a customized design [17][50]. Recently, hydrogel scaffolds have been tried [18][51]. These hydrogels are designed to provide cells with a fully hydrated 3D environment, comparable to the native tissue ECM. However, hydrogels have inadequate mechanical properties that are unfavorable for embedded cells or become too weak for application to the musculoskeletal system. Currently, the 3D hydrogel-enhanced approach provides a foundation to produce biologically and mechanically compatible fabric constructions. Thus, understanding the approaches to make 3D scaffolds (dis cussed in Section 4) is critical, as they must provide the proper structure to promote homogeneous cell proliferation and/or cell differentiation and, after implantation, host tissue growth. It is important to consider the pore architecture—mechanical and biological properties—strengthening the cellular interconnection. This must be limited within an established design to allow the development of the tissues.
Before the existence of osteochondral TE and the development of centrifugal technology, few artificial materials offered dual bioactivity both for cartilage regeneration and subchondral regeneration [19][20][52,53]. As previously mentioned, currently there are several treatments for osteochondral defects (e.g., palliative, restorative, abrasion arthroplasty, chondroplasty, and arthroscopic debridement). Still, they all have limitations, including slower remodeling, the need for post-operation rehabilitation, the possibility of disease transmission, and the possibility of immune reactions. Another strategy that has been used is the transplantation of bioactive materials, such as autologous chondrocytes or cartilaginous tissue, to create defective regions for the osteochondral zone. Several limitations restrict its use, such as the slow maturation of the tissue and long-term recovery [21][54]. Therefore, it is safe to state that the successful treatment of osteochondral tissue is still a paramount challenge.
In TE, “biomimetics” applies when defining the design and manufacture of scaffolds capable of imitating biological tissue, providing better integration with cartilage and surrounding bone tissue. Osteochondral regeneration, due to the different cartilages and subchondral bone composition, together with biochemical, biomechanical, and biological properties, becomes a big challenge [22][55]. Therefore, to obtain a biomimetic scaffold it is necessary to provide the different mechanical and biological signals necessary and appropriate to allow the osteochondral regeneration [23][56]. Over the past decades, there has been a wide variety of technologies for manufacturing 3D scaffolds for osteochondral TE. However, these methods, called traditional methods, are still complex and of low efficiency, since they cannot biologically imitate the native microstructure. To solve these problems, the implementation of AM 3D scaffolds has emerged, which can imitate as closely as possible the anisotropic nature of the ECM and the heterogeneity of the osteochondral tissue [19][52].
Scaffolds for osteochondral regeneration have several requirements, such as being degradable, biocompatible, as biomimetic as possible, mechanically stable, clinically transferable, and able to be printed and having a viable architecture [24][57].
