Current Advances in Regenerative Medicine for Articular Cartilage Injury: Progress and Market Trends

Special Article: Osteoarthritis

Foot Ankle Stud. 2023; 5(1): 1030.

Current Advances in Regenerative Medicine for Articular Cartilage Injury: Progress and Market Trends

Zohreh Arabpour1#; Farzad Parvizpour6#; Maryam Moradi2; Nikan Zargarzadeh3; Mahnaz Nazari4; Heewa Rashnavadi3; Sanaz Dehghani1,5; Marzieh Latifi5; Arefeh Jafarian1*

1Iranian Tissue Bank and Research Center, Tehran University of Medical Sciences, Tehran, Iran

2School of Medicine, Iran University of Medical Sciences, Tehran, Iran

3School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

4Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

5Organ Procurement Unit, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran

6Department of Molecular Medicine, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

*Corresponding author: Arefeh Jafarian Iranian tissue bank and research center, Tehran University of Medical Sciences, Tehran, Iran. Email: f-parvizpour@razi.tums.ac.ir

#These authors have been contributed equally to this article.

Received: September 14, 2023 Accepted: November 03, 2023 Published: N0vember 10, 2023

Abstract

Today, treatments of cartilage and osteochondral lesions are routine clinical procedures. Treatment of large Articular Cartilage (AC) defects is technically difficult and complex, often accompanied by failure. Articular cartilage is a highly specialized connective tissue with limited ability to repair itself after injury due to a lack of blood vessels, lymph, and nerves. Therefore, without sufficient and potent intervention, cartilage lesions can easily lead to progressive tissue degeneration, disabling joint pain, and eventually the degenerative disease, Osteoarthritis (OA). Various treatments for cartilage regeneration have shown encouraging results, but unfortunately, none of them have been the perfect solution. New minimally invasive and effective techniques are being developed. The development of tissue engineering technology has created strong promise to engineer or regenerate functional and healthy articular cartilage. In this technology, potential stem cell sources are mainly supplied with pluripotent stem cells and mesenchymal stem cells from various sources. In the meantime, some such as BioSeed®-C and NOVOCART® have been marketed. In this review, the common techniques of articular cartilage reconstruction and the clinical application of articular cartilage tissue engineering are described in detail.

Keywords: Articular cartilage; Cartilage gene therapy; Cartilage product; Regenerative medicine; Tissue engineering; Transplantation methods

Introduction

Articular cartilage is a complex organ with connective tissue that has a limited repair capacity [1]. Usually, small lesions that penetrate the subcutaneous bone layer are repaired by creating a fibrous scar, but extensive injuries require medical intervention. In recent years, a variety of surgical and non-surgical treatments have been developed to repair cartilage, but the complete treatment of lesions larger than 2-4 mm of the articular cartilage remains a therapeutic challenge [2].

Recently, tissue engineering and regenerative medicine using stem cells and biomaterials were able to revolutionize tissue and organ regeneration [3]. This method allows custom design for tissue regeneration and offers tissue replacement that mimics native tissue without adverse effects such as suppression of the immune system or contamination of the donor disease [4]. One of the major challenges in this method is designing appropriate scaffolds with the structure of native tissues [5]. Tissue-engineered cartilage must be highly compatible to prevent acute immune response after transplantation, also it must have special properties such as the ability to combine with subcutaneous bone and adjacent cartilage, mimic the mechanical properties of natural cartilage to maintain function, and withstand long-term loads [6].

In this study, new methods of repairing extensive joint cartilage injuries using different cellular sources and synthesis techniques are reviewed and a list of commercial products used in the treatment of cartilage injuries is presented.

Tissue Engineering Strategies for Articular Cartilage Regeneration

Current strategies for repairing articular cartilage, including surgical and non-surgical treatments, have not yet provided long-term solutions for repairing large articular cartilage lesions [2]. Tissue engineering and regenerative medicine can provide alternative treatment strategies using appropriate scaffolding, cells, and biochemical and biomechanical stimuli [3]. This method allows a custom design to regenerate native tissue without side effects such as infection transmission or the use of immunosuppressive drugs [5]. Tissue-engineered cartilage must be biocompatible and can connect with the subcutaneous bone and adjacent cartilage. In addition, it should be able to mimic the physical and mechanical properties of native tissue [6].

Scaffold for Articular Cartilage Tissue Engineering

In recent years, various scaffolds including synthetic or natural materials such as polylactides, polyglycolide, hyaluronic acid, collagen, and silk have been studied for articular cartilage tissue engineering [7]. In previous studies, a matrix derived from decellularized cartilage was used as a natural source for scaffolding in cartilage regeneration. This substrate was able to synthesize the extracellular matrix of cartilage by inhibiting the hypertrophic differentiation of embedded Mesenchymal Stem Cells (MSCs). The results also showed that the synthesized extracellular matrix could support the differentiation of mesenchymal stem cells into fibroblast and fibrochondrocyte phenotypes [8]. Hydrogels are another class of materials used as scaffolds in articular cartilage tissue engineering. These materials have received a lot of attention due to their injectability and ductility compatible with irregular defects of articular cartilage. On the other hand, due to the advent of 3D printing technology, achieving the right hydrogel can be a big step in the design and customization of graft implants in the repair of cartilage defects. In addition, in this technology, cells and growth factors can be included in the scaffold structure during synthesis [9]. In previous research has used synthetic polymers such as polycaprolactone and polylactic acid, as well as natural sources such as alginate and hyaluronan to create custom anatomical scaffolds for articular cartilage in 3D printers [10]. Stimuli-responsive hydrogels or smart hydrogels are a group of hydrogels in which a specific transition occurs due to small changes in the environment [11]. This group of hydrogels in response to various external physicochemical factors such as chemical stimuli [12], temperature changes [13], solvent type [14], pH [15], ionic strength [16], wavelength or light intensity [17] or electric fields and magnetically are sensitive [18].

The use of smart hydrogels in actuators, sensors, scaffolds, and drug delivery has received considerable attention because of their rapid response to environmental stimuli, which can cause significant changes. Designing scaffolds based on intelligent injection hydrogels with nanostructured properties and rapid response to stimuli can be an appropriate option to meet all the essential needs of cartilage regeneration [11]. One of the necessities of transferring the functional properties of native tissue to the product of tissue engineering is the design and production of scaffolds that can mimic the mechanical properties of native tissue. For example, studies have shown that polyethylene glycol and chondroitin sulfate-derived hydrogels produce structures with stiffness gradients (0.005-0.06 MPa) that can mimic the glycosaminoglycan gradient in articular cartilage [19].

Current Cell Sources for Articular Cartilage Damage

The ultimate goal of cartilage repair is to find an ideal cell source that can be easily isolated, expanded, and cultured to express and synthesize cartilage-specific Extracellular Matrices (ECM), such as type II collagen and aggrecan. Stem cells and chondrocytes have been investigated for their potential as viable cell sources for cartilage tissue engineering and validated in animal models (Figure 1) [20].

Citation: Arabpour Z, Parvizpour F, Moradi M, Zargarzadeh N, Nazari M, et al. Current Advances in Regenerative Medicine for Articular Cartilage Injury: Progress and Market Trends. Foot Ankle Stud. 2023; 5(1): 1030.