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    Review of cartilage regeneration through injectable microgels

  • Hossein Javid,1,* Fahimeh Taheri,2 Fateme Kooshki,3 Mohammadjavad Amini noghondar,4 Zahra Javadi,5 ZahraSadat Malekjafarian,6
    1. Department of Medical Laboratory Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran
    2. Department of Medical Laboratory Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran
    3. Department of Medical Laboratory Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran
    4. Department of Medical Laboratory Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran
    5. Department of Medical Laboratory Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran
    6. Department of Medical Laboratory Sciences, Varastegan Institute for Medical Sciences, Mashhad, Iran


  • Introduction: One of the tissues in the body that is faced with regeneration difficulties is cartilage [1-7]. Common approaches used for treating cartilage abnormalities are stem cell injection and cartilage tissue engineering. Stem cell injections result in poor cell survival, whereas cartilage tissue engineering leaves a large wound and fails to fill uneven flaws after implantation. However, because of their customizable structure and capacity to accommodate bioactive substances, and their ability to be locally supplied to fill irregular defects, injectable hydrogels have been employed for cartilage regeneration [1, 7]. Natural materials such as collagen, alginate, hyaluronic acid, chitosan, and gelatin or synthetic materials such as polyethylene glycol can be utilized to make hydrogels [5]. Microfluidic technology and photopolymerization processes are used to create microgels, which are growth factor-loaded methacrylated hyaluronic acid and heparin blend MGs that can recruit endogenous mesenchymal stem cells and promote chondrogenic differentiation [8]. Microfluidic microgel is an appropriate cell carrier for preventing injection-induced shear stress damage to encapsulated stem cells [5, 8]. As a result, we believe that the microgel-based strategy that has emerged as one of the most promising types of cartilage regeneration has a bright future in novel methods of articular cartilage repair.
  • Methods: We used PubMed, Medline, Google scholar, science direct, and Embassy databases to conduct a systematic literature search using cartilage, Mesenchyme stem cell, Biologist, PRP, ACI as keywords in our search terms. We considered a language limitation as English and a time limit for 2019-2022 due to the increase and advances made in the subject in this period. The criteria for including studies in our review encompassed clinical studies on ASC injection conducted on humans for cartilage regeneration. We screened 320 articles using the PRISMA checklist to exclude duplicates and improper studies. We discovered clinical investigations on ASC therapies for cartilage abnormalities in 17 articles. Also, a scoping evaluation of the existing scientific literature for hip biologics was conducted, with evidence for hyaluronic acid available (HA), platelet-rich plasma (PRP), stem/stromal cells, microfracture, mosaicplasty, osteochondral allograft, and cell-based therapies investigated.
  • Results: As mentioned, there are several different methods for engineering cartilage, and each has its advantages and disadvantages. Since articular cartilage is engaged in weight-bearing and has a relatively low intrinsic healing potential, there are various barriers to regenerative therapies [9]. As a result, it is critical to employ proper tissue engineering materials and cell types in cartilage regeneration [9]. There are two possible prevention techniques for hyaline cartilage fibrosis: 1) Reshape the injury's microenvironment. 2) Increase the migration of endogenous skeletal or mesenchymal stem cells to the articular cartilage [6]. The response of endogenous cells is one of the sources of cell-laden microgel. In addition to the influence on encapsulated cell types, the microgels may affect endogenous cells, which substantially impacts the entire healing process [7]. Three main strategies used for tissue-engineering articular cartilage are: 1) Cell-scaffold construct. 2) Scaffold-free 3) Cell-free. The last method utilizes endogenous stem cells indirectly [4]. The scaffold-based strategy has limitations, including unavailable cell sources, morbidity at the donor location, and chondrocyte phenotypic instability in culture [10]. The risks of morbidity associated with arthroplasty are significant. Another challenge of surgery is the painful repercussions and short lifespan of implanted prostheses [11] [12].
  • Conclusion: Mesenchymal stem cell-based therapies offer a great way to revolutionize the treatment of cartilage defects, and it has been shown that the mechanisms of mesenchymal stem cell cartilage regeneration are related to nutritional factors and direct grafting. Exosomes are very important as extracellular vesicles among nutritional factors [12] [9]. There are several difficulties related to isolating and growing, differentiating, and preparing mesenchymal stem cells for placement in degenerated joints, and it can be dangerous if these cells are exposed to abnormal physical loads on anatomical structures. Therefore, future reconstructive medical strategies must address these remaining concerns [9]. More investigations need to be done into this area. Better-designed studies are required to elucidate the precise mechanism of action of the treatment and the general application of these stem cells to treat OA with cartilage regeneration. [12].
  • Keywords: Cartilage regeneration, Cell-laden injectable microgels, Articular repair, Challenges for Cartilage