Cartilage Tissue Engineering Approaches Need to Assess Fibrocartilage When Hydrogel Constructs Are Mechanically Loaded

Chondrocytes that are impregnated within hydrogel constructs sense applied mechanical force and can respond by expressing collagens, which are deposited into the extracellular matrix (ECM). The intention of most cartilage tissue engineering is to form hyaline cartilage, but if mechanical stimulation pushes the ratio of collagen type I (Col1) to collagen type II (Col2) in the ECM too high, then fibrocartilage can form instead. With a focus on Col1 and Col2 expression, the first part of this article reviews the latest studies on hyaline cartilage regeneration within hydrogel constructs that are subjected to compression forces (one of the major types of the forces within joints) in vitro. Since the mechanical loading conditions involving compression and other forces in joints are difficult to reproduce in vitro, implantation of hydrogel constructs in vivo is also reviewed, again with a focus on Col1 and Col2 production within the newly formed cartilage. Furthermore, mechanotransduction pathways that may be related to the expression of Col1 and Col2 within chondrocytes are reviewed and examined. Also, two recently-emerged, novel approaches of load-shielding and synchrotron radiation (SR)–based imaging techniques are discussed and highlighted for future applications to the regeneration of hyaline cartilage. Going forward, all cartilage tissue engineering experiments should assess thoroughly whether fibrocartilage or hyaline cartilage is formed.

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In vitro and in vivo imaging techniques for cartilage tissue engineering

Journal of Biomechanics ◽

10.1016/s0021-9290(06)84829-3 ◽

2006 ◽

Vol 39 ◽

pp. S447

Author(s):

S. Tiwari ◽

S. Pollok ◽

H. Notbohm ◽

R. Reis ◽

B. Vollmar ◽

...

Keyword(s):

Tissue Engineering ◽

In Vivo Imaging ◽

Imaging Techniques ◽

Cartilage Tissue Engineering ◽

Cartilage Tissue

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Chondrogenic Potential of Dental-Derived Mesenchymal Stromal Cells

Osteology ◽

10.3390/osteology1030016 ◽

2021 ◽

Vol 1 (3) ◽

pp. 149-174

Author(s):

Naveen Jeyaraman ◽

Gollahalli Shivashankar Prajwal ◽

Madhan Jeyaraman ◽

Sathish Muthu ◽

Manish Khanna

Keyword(s):

Tissue Engineering ◽

Mesenchymal Stromal Cells ◽

Tissue Regeneration ◽

Stromal Cells ◽

Cartilage Tissue Engineering ◽

Cartilage Regeneration ◽

Cartilage Tissue ◽

Dentin Matrix

The field of tissue engineering has revolutionized the world in organ and tissue regeneration. With the robust research among regenerative medicine experts and researchers, the plausibility of regenerating cartilage has come into the limelight. For cartilage tissue engineering, orthopedic surgeons and orthobiologists use the mesenchymal stromal cells (MSCs) of various origins along with the cytokines, growth factors, and scaffolds. The least utilized MSCs are of dental origin, which are the richest sources of stromal and progenitor cells. There is a paradigm shift towards the utilization of dental source MSCs in chondrogenesis and cartilage regeneration. Dental-derived MSCs possess similar phenotypes and genotypes like other sources of MSCs along with specific markers such as dentin matrix acidic phosphoprotein (DMP) -1, dentin sialophosphoprotein (DSPP), alkaline phosphatase (ALP), osteopontin (OPN), bone sialoprotein (BSP), and STRO-1. Concerning chondrogenicity, there is literature with marginal use of dental-derived MSCs. Various studies provide evidence for in-vitro and in-vivo chondrogenesis by dental-derived MSCs. With such evidence, clinical trials must be taken up to support or refute the evidence for regenerating cartilage tissues by dental-derived MSCs. This article highlights the significance of dental-derived MSCs for cartilage tissue regeneration.

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Adipose-Derived Mesenchymal Stem Cell Chondrospheroids Cultured in Hypoxia and a 3D Porous Chitosan/Chitin Nanocrystal Scaffold as a Platform for Cartilage Tissue Engineering

International Journal of Molecular Sciences ◽

10.3390/ijms21031004 ◽

2020 ◽

Vol 21 (3) ◽

pp. 1004 ◽

Cited By ~ 8

Author(s):

Veronica Zubillaga ◽

Ana Alonso-Varona ◽

Susana C. M. Fernandes ◽

Asier M. Salaberria ◽

Teodoro Palomares

Keyword(s):

Tissue Engineering ◽

Articular Cartilage ◽

Collagen Type ◽

Porous Scaffold ◽

Cartilage Tissue Engineering ◽

Cartilage Regeneration ◽

Cartilage Tissue ◽

Type I ◽

Low Oxygen ◽

Porous Chitosan

Articular cartilage degeneration is one of the most common causes of pain and disability in middle-aged and older people. Tissue engineering (TE) has shown great therapeutic promise for this condition. The design of cartilage regeneration constructs must take into account the specific characteristics of the cartilaginous matrix, as well as the avascular nature of cartilage and its cells’ peculiar arrangement in isogenic groups. Keeping these factors in mind, we have designed a 3D porous scaffold based on genipin-crosslinked chitosan/chitin nanocrystals for spheroid chondral differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) induced in hypoxic conditions. First, we demonstrated that, under low oxygen conditions, the chondrospheroids obtained express cartilage-specific markers including collagen type II (COL2A1) and aggrecan, lacking expression of osteogenic differentiation marker collagen type I (COL1A2). These results were associated with an increased expression of hypoxia-inducible factor 1α, which positively directs COL2A1 and aggrecan expression. Finally, we determined the most suitable chondrogenic differentiation pattern when hASC spheroids were seeded in the 3D porous scaffold under hypoxia and obtained a chondral extracellular matrix with a high sulphated glycosaminoglycan content, which is characteristic of articular cartilage. These findings highlight the potential use of such templates in cartilage tissue engineering.

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Cartilage Tissue Engineering Using Mesenchymal Stem Cells and 3D Chitosan Scaffolds – In vitro and in vivo Assays

Biomaterials Science and Engineering ◽

10.5772/25085 ◽

2011 ◽

Author(s):

Natalia Martins ◽

Alessandra Arcoverde ◽

Juliana Lott ◽

Viviane Silva ◽

Dawidson Gomes ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cartilage Tissue Engineering ◽

Cartilage Tissue ◽

In Vivo Assays ◽

Chitosan Scaffolds

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TRENDS AND CHALLENGES OF CARTILAGE TISSUE ENGINEERING

Biomedical Engineering Applications Basis and Communications ◽

10.4015/s1016237209001209 ◽

2009 ◽

Vol 21 (03) ◽

pp. 149-155 ◽

Cited By ~ 2

Author(s):

Hsu-Wei Fang

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Growth Factors ◽

Bone Cells ◽

Cartilage Tissue Engineering ◽

Bioactive Molecules ◽

In Vivo Studies ◽

Cartilage Tissue

Cartilage injuries may be caused by trauma, biomechanical imbalance, or degenerative changes of joint. Unfortunately, cartilage has limited capability to spontaneous repair once damaged and may lead to progressive damage and degeneration. Cartilage tissue-engineering techniques have emerged as the potential clinical strategies. An ideal tissue-engineering approach to cartilage repair should offer good integration into both the host cartilage and the subchondral bone. Cells, scaffolds, and growth factors make up the tissue engineering triad. One of the major challenges for cartilage tissue engineering is cell source and cell numbers. Due to the limitations of proliferation for mature chondrocytes, current studies have alternated to use stem cells as a potential source. In the recent years, a lot of novel biomaterials has been continuously developed and investigated in various in vitro and in vivo studies for cartilage tissue engineering. Moreover, stimulatory factors such as bioactive molecules have been explored to induce or enhance cartilage formation. Growth factors and other additives could be added into culture media in vitro, transferred into cells, or incorporated into scaffolds for in vivo delivery to promote cellular differentiation and tissue regeneration.Based on the current development of cartilage tissue engineering, there exist challenges to overcome. How to manipulate the interactions between cells, scaffold, and signals to achieve the moderation of implanted composite differentiate into moderate stem cells to differentiate into hyaline cartilage to perform the optimum physiological and biomechanical functions without negative side effects remains the target to pursue.

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Advanced Hydrogels for Cartilage Tissue Engineering: Recent Progress and Future Directions

Polymers ◽

10.3390/polym13234199 ◽

2021 ◽

Vol 13 (23) ◽

pp. 4199

Author(s):

Mahshid Hafezi ◽

Saied Nouri Khorasani ◽

Mohadeseh Zare ◽

Rasoul Esmaeely Neisiany ◽

Pooya Davoodi

Keyword(s):

Tissue Engineering ◽

Cartilage Tissue Engineering ◽

Cartilage Regeneration ◽

Biomechanical Properties ◽

Tissue Growth ◽

Cartilage Tissue ◽

Self Healing ◽

Advantages And Disadvantages ◽

Wide Range

Cartilage is a tension- and load-bearing tissue and has a limited capacity for intrinsic self-healing. While microfracture and arthroplasty are the conventional methods for cartilage repair, these methods are unable to completely heal the damaged tissue. The need to overcome the restrictions of these therapies for cartilage regeneration has expanded the field of cartilage tissue engineering (CTE), in which novel engineering and biological approaches are introduced to accelerate the development of new biomimetic cartilage to replace the injured tissue. Until now, a wide range of hydrogels and cell sources have been employed for CTE to either recapitulate microenvironmental cues during a new tissue growth or to compel the recovery of cartilaginous structures via manipulating biochemical and biomechanical properties of the original tissue. Towards modifying current cartilage treatments, advanced hydrogels have been designed and synthesized in recent years to improve network crosslinking and self-recovery of implanted scaffolds after damage in vivo. This review focused on the recent advances in CTE, especially self-healing hydrogels. The article firstly presents the cartilage tissue, its defects, and treatments. Subsequently, introduces CTE and summarizes the polymeric hydrogels and their advances. Furthermore, characterizations, the advantages, and disadvantages of advanced hydrogels such as multi-materials, IPNs, nanomaterials, and supramolecular are discussed. Afterward, the self-healing hydrogels in CTE, mechanisms, and the physical and chemical methods for the synthesis of such hydrogels for improving the reformation of CTE are introduced. The article then briefly describes the fabrication methods in CTE. Finally, this review presents a conclusion of prevalent challenges and future outlooks for self-healing hydrogels in CTE applications.

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Mechano-Active Cartilage Tissue Engineering

Advances in Science and Technology ◽

10.4028/www.scientific.net/ast.49.189 ◽

2006 ◽

Vol 49 ◽

pp. 189-196

Author(s):

Soo Hyun Kim ◽

Young Mee Jung ◽

Sang Heon Kim ◽

Young Ha Kim ◽

Jun Xie ◽

...

Keyword(s):

Tissue Engineering ◽

Dynamic Compression ◽

Cartilage Tissue Engineering ◽

Compressive Deformation ◽

Cartilage Tissue ◽

Cartilaginous Tissue ◽

Pressing Method ◽

Safranin O

To engineer cartilaginous constructs with a mechano-active scaffold and dynamic compression was performed for effective cartilage tissue engineering. Mechano-active scaffolds were fabricated from very elastic poly(L-lactide-co-ε-carprolactone)(5:5). The scaffolds with 85 % porosity and 300~500 μm pore size were prepared by a gel-pressing method. The scaffolds were seeded with chondrocytes and the continuous compressive deformation of 5% strain was applied to cell-polymer constructs with 0.1Hz to evaluate for the effect of dynamic compression for regeneration of cartilage. Also, the chondrocytes-seeded constructs stimulated by the continuous compressive deformation of 5% strain with 0.1Hz for 10 days and 24 days respectively were implanted in nude mice subcutaneously to investigate their biocompatibility and cartilage formation. From biochemical analyses, chondrogenic differentiation was sustained and enhanced significantly and chondrial extracellular matrix was increased through mechanical stimulation. Histological analysis showed that implants stimulated mechanically formed mature and well-developed cartilaginous tissue, as evidenced by chondrocytes within lacunae. Masson’s trichrome and Safranin O staining indicated an abundant accumulation of collagens and GAGs. Also, ECM in constructs was strongly immuno-stained with anti-rabbit collagen type II antibody. Consequently, the periodic application of dynamic compression can improve the quality of cartilaginous tissue formed in vitro and in vivo.

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Gellan Gum Injectable Hydrogels for Cartilage Tissue Engineering Applications: In Vitro Studies and Preliminary In Vivo Evaluation

Tissue Engineering Part A ◽

10.1089/ten.tea.2009.0117 ◽

2010 ◽

Vol 16 (1) ◽

pp. 343-353 ◽

Cited By ~ 104

Author(s):

João T. Oliveira ◽

Tírcia C. Santos ◽

Luís Martins ◽

Ricardo Picciochi ◽

Alexandra P. Marques ◽

...

Keyword(s):

Tissue Engineering ◽

Cartilage Tissue Engineering ◽

Gellan Gum ◽

In Vitro Studies ◽

Cartilage Tissue ◽

Engineering Applications ◽

In Vivo Evaluation ◽

Injectable Hydrogels

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Spatiotemporal regulation of endogenous MSCs using a functional injectable hydrogel system for cartilage regeneration

NPG Asia Materials ◽

10.1038/s41427-021-00339-3 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Yunsheng Dong ◽

Yufei Liu ◽

Yuehua Chen ◽

Xun Sun ◽

Lin Zhang ◽

...

Keyword(s):

Cartilage Tissue Engineering ◽

Cartilage Regeneration ◽

Cartilage Tissue ◽

Cartilage Defects ◽

In Vivo Experiments ◽

Spatiotemporal Regulation ◽

Stromal Cell Derived Factor ◽

Hydrogel System

AbstractHydrogels have been extensively favored as drug and cell carriers for the repair of knee cartilage defects. Recruiting mesenchymal stem cells (MSCs) in situ to the defect region could reduce the risk of contamination during cell delivery, which is a highly promising strategy to enhance cartilage repair. Here, a cell-free cartilage tissue engineering (TE) system was developed by applying an injectable chitosan/silk fibroin hydrogel. The hydrogel system could release first stromal cell-derived factor-1 (SDF-1) and then kartogenin (KGN) in a unique sequential drug release mode, which could spatiotemporally promote the recruitment and chondrogenic differentiation of MSCs. This system showed good performance when formulated with SDF-1 (200 ng/mL) and PLGA microspheres loaded with KGN (10 μΜ). The results showed that the hydrogel had good injectability and a reticular porous structure. The microspheres were distributed uniformly in the hydrogel and permitted the sequential release of SDF-1 and KGN. The results of in vitro experiments showed that the hydrogel system had good cytocompatibility and promoted the migration and differentiation of MSCs into chondrocytes. In vivo experiments on articular cartilage defects in rabbits showed that the cell-free hydrogel system was beneficial for cartilage regeneration. Therefore, the composite hydrogel system shows potential for application in cell-free cartilage TE.

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