Recombinant human midkine stimulates proliferation and decreases dedifferentiation of auricular chondrocytes in vitro

Autologous chondrocyte implantation (ACI) is widely used for the repair of cartilage defects. However, due to the lack of chondrocyte growth factor and dedifferentiation of the cultured primary chondrocytes, cell source has limited the clinical potential of ACI. Auricular cartilage is an attractive potential source of cells for cartilage tissue engineering. Here we demonstrated that recombinant human midkine (rhMK) significantly promoted proliferation of rat primary auricular chondrocytes cultured and passaged in monolayer, which was mediated by the activation of mitogen-activated protein kinase and phosphoinositide 3-kinase pathways. Furthermore, rhMK attenuated the dedifferentiation of cultured chondrocytes by maintaining the expression of chondrocyte-specific matrix proteins during culture expansion and passage. Importantly, rhMK-expanded chondrocytes reserved their full chondrogenic potential and redifferentiated into elastic chondrocytes after being cultured in high density. The results suggest that rhMK may be used for the preparation of chondrocytes in cartilage tissue engineering.

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Cartilage tissue engineering for craniofacial reconstruction

Archives of Plastic Surgery ◽

10.5999/aps.2020.01095 ◽

2020 ◽

Vol 47 (5) ◽

pp. 392-403 ◽

Cited By ~ 1

Author(s):

Min-Sook Kim ◽

Hyung-Kyu Kim ◽

Deok-Woo Kim

Keyword(s):

Tissue Engineering ◽

Cartilage Tissue Engineering ◽

Cartilage Tissue ◽

Cartilage Defects ◽

Craniofacial Reconstruction ◽

Medical Expenses ◽

Basic Concepts ◽

Regenerate Tissue ◽

Made In

Severe cartilage defects and congenital anomalies affect millions of people and involve considerable medical expenses. Tissue engineering offers many advantages over conventional treatments, as therapy can be tailored to specific defects using abundant bioengineered resources. This article introduces the basic concepts of cartilage tissue engineering and reviews recent progress in the field, with a focus on craniofacial reconstruction and facial aesthetics. The basic concepts of tissue engineering consist of cells, scaffolds, and stimuli. Generally, the cartilage tissue engineering process includes the following steps: harvesting autologous chondrogenic cells, cell expansion, redifferentiation, <i>in vitro</i> incubation with a scaffold, and transfer to patients. Despite the promising prospects of cartilage tissue engineering, problems and challenges still exist due to certain limitations. The limited proliferation of chondrocytes and their tendency to dedifferentiate necessitate further developments in stem cell technology and chondrocyte molecular biology. Progress should be made in designing fully biocompatible scaffolds with a minimal immune response to regenerate tissue effectively.

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Research Progress of Tissue-Engineered Cartilage in Repairing Cartilage Defects

Science of Advanced Materials ◽

10.1166/sam.2020.3704 ◽

2020 ◽

Vol 12 (1) ◽

pp. 66-74

Author(s):

Yuan-Jia He ◽

Shuang Lin ◽

Qiang Ao

Keyword(s):

Tissue Engineering ◽

Cartilage Tissue Engineering ◽

Biomechanical Properties ◽

The Body ◽

Research Progress ◽

Cartilage Tissue ◽

Cartilage Defects ◽

Biomaterial Scaffolds ◽

Seed Cells

Due to the unsatisfactory outcome of current clinical treatment, tissue engineering technology has become a promising approach for the treatment of cartilage defects. Typical cartilage tissue engineering uses seed cells that have been expanded in vitro to implant into various biomaterial scaffolds that are biocompatible and are gradually degraded and absorbed in the body, with or without physical/chemical factors mimicking the cartilage microenvironment, to regenerate cartilage tissue with similar biochemical and biomechanical properties to natural cartilage tissue. Therefore, we summarise the three aspects of seed cells, biological scaffolds, and factors/signals.

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Novel Biologically Inspired Nanostructured Scaffolds for Directing Chondrogenic Differentiation of Mesenchymal Stem Cells

MRS Proceedings ◽

10.1557/opl.2013.181 ◽

2013 ◽

Vol 1498 ◽

pp. 59-66 ◽

Cited By ~ 1

Author(s):

Benjamin Holmes ◽

Nathan J. Castro ◽

Jian Li ◽

Lijie Grace Zhang

Keyword(s):

Carbon Nanotubes ◽

Tissue Engineering ◽

Stem Cells ◽

Cartilage Tissue Engineering ◽

Modern Medicine ◽

Cartilage Tissue ◽

Cartilage Defects ◽

Medical Problems ◽

Biologically Inspired

ABSTRACTCartilage defects, which are caused by a variety of reasons such as traumatic injuries, osteoarthritis, or osteoporosis, represent common and severe clinical problems. Each year, over 6 million people visit hospitals in the U.S. for various knee, wrist, and ankle problems. As modern medicine advances, new and novel methodologies have been explored and developed in order to solve and improve current medical problems. One of the areas of investigation is tissue engineering [1, 2]. Since cartilage matrix is nanocomposite, the goal of the current work is to use nanomaterials and nanofabrication methods to create novel biologically inspired tissue engineered cartilage scaffolds for facilitating human bone marrow mesenchymal stem cell (MSC) chondrogenesis. For this purpose, through electrospinning techniques, we designed a series of novel 3D biomimetic nanostructured scaffolds based on carbon nanotubes and biocompatible poly(L-lactic acid) (PLLA) polymers. Specifically, a series of electrospun fibrous PLLA scaffolds with controlled fiber dimension and surface nanoporosity were fabricated in this study. In vitro hMSC studies showed that stem cells prefer to attach in the scaffolds with smaller fiber diameter or suitable nanoporous structures. More importantly, our in vitro differentiation results demonstrated that incorporation of the biomimetic carbon nanotubes and poly L-lysine coating can induce GAG and collagen synthesis that is indicative of chondrogenic differentiations of MSCs. Our novel scaffolds also performed better than controls, which make them promising for cartilage tissue engineering applications.

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Neural Crest-Derived Chondrocytes Isolation for Tissue Engineering in Regenerative Medicine

Cells ◽

10.3390/cells9040962 ◽

2020 ◽

Vol 9 (4) ◽

pp. 962

Author(s):

Monica Salamone ◽

Salvatrice Rigogliuso ◽

Aldo Nicosia ◽

Marcello Tagliavia ◽

Simona Campora ◽

...

Keyword(s):

Tissue Engineering ◽

Cartilage Tissue Engineering ◽

Enzymatic Digestion ◽

Cartilage Tissue ◽

Cartilage Defects ◽

Nasal Cartilage ◽

Tissue Dissociation ◽

In Vitro Expansion ◽

First Time

Chondrocyte transplantation has been successfully tested and proposed as a clinical procedure aiming to repair articular cartilage defects. However, the isolation of chondrocytes and the optimization of the enzymatic digestion process, as well as their successful in vitro expansion, remain the main challenges in cartilage tissue engineering. In order to address these issues, we investigated the performance of recombinant collagenases in tissue dissociation assays with the aim of isolating chondrocytes from bovine nasal cartilage in order to establish the optimal enzyme blend to ensure the best outcomes of the overall procedure. We show, for the first time, that collagenase H activity alone is required for effective cartilage digestion, resulting in an improvement in the yield of viable cells. The extracted chondrocytes proved able to grow and activate differentiation/dedifferentiation programs, as assessed by morphological and gene expression analyses.

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Development of a Biomimetic Electrospun Microfibrous Scaffold With Multiwall Carbon Nanotubes for Cartilage Regeneration

ASME 2013 2nd Global Congress on NanoEngineering for Medicine and Biology ◽

10.1115/nemb2013-93202 ◽

2013 ◽

Cited By ~ 1

Author(s):

Benjamin Holmes ◽

Nathan J. Castro ◽

Jian Li ◽

Lijie Grace Zhang

Keyword(s):

Carbon Nanotubes ◽

Tissue Engineering ◽

Cartilage Tissue Engineering ◽

Multiwall Carbon Nanotubes ◽

Cartilage Regeneration ◽

Modern Medicine ◽

Cartilage Tissue ◽

Cartilage Defects ◽

Medical Problems

Cartilage defects, which are caused by a variety of reasons such as traumatic injuries, osteoarthritis, or osteoporosis, represent common and severe clinical problems. Each year, over 6 million people visit hospitals in the U.S. for various knee, wrist, and ankle problems. As modern medicine advances, new and novel methodologies have been explored and developed in order to solve and improve current medical problems. One of the areas of investigation that has thus far proven to be very promising is tissue engineering [1, 2]. Since cartilage matrix is nanocomposite, the goal of the current work is to use nanomaterials and nanofabrication methods to create novel biologically inspired tissue engineered cartilage scaffolds for facilitating human bone marrow mesenchymal stem cell (MSC) chondrogenesis. For this purpose, through electrospinning techniques, we designed a series of novel 3D biomimetic nanostructured scaffolds based on carbon nanotubes and biocompatible poly(L-lactic acid) (PLLA) polymers. Specifically, a series of electrospun fibrous PLLA scaffolds with controlled fiber dimension were fabricated in this study. In vitro hMSC studies showed that stem cells prefer to attach in the scaffolds with smaller fiber diameter. More importantly, our in vitro differentiation results demonstrated that incorporation of the biomimetic carbon nanotubes and poly L-lysine coating can induce more chondrogenic differentiations of MSCs than controls, which make them promising for cartilage tissue engineering applications.

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Potential of 3-D tissue constructs engineered from bovine chondrocytes/silk fibroin-chitosan for in vitro cartilage tissue engineering

Biomaterials ◽

10.1016/j.biomaterials.2011.04.061 ◽

2011 ◽

Vol 32 (25) ◽

pp. 5773-5781 ◽

Cited By ~ 134

Author(s):

Nandana Bhardwaj ◽

Quynhhoa T. Nguyen ◽

Albert C. Chen ◽

David L. Kaplan ◽

Robert L. Sah ◽

...

Keyword(s):

Tissue Engineering ◽

Silk Fibroin ◽

Cartilage Tissue Engineering ◽

Cartilage Tissue ◽

Tissue Constructs

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Calcium/Cobalt Alginate Beads as Functional Scaffolds for Cartilage Tissue Engineering

Stem Cells International ◽

10.1155/2016/2030478 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 22

Author(s):

Stefano Focaroli ◽

Gabriella Teti ◽

Viviana Salvatore ◽

Isabella Orienti ◽

Mirella Falconi

Keyword(s):

Tissue Engineering ◽

Bone Morphogenetic Proteins ◽

Transforming Growth Factor ◽

Cartilage Tissue Engineering ◽

Biomechanical Properties ◽

Alginate Beads ◽

Cartilage Tissue ◽

Self Healing ◽

Tissue Replacement

Articular cartilage is a highly organized tissue with complex biomechanical properties. However, injuries to the cartilage usually lead to numerous health concerns and often culminate in disabling symptoms, due to the poor intrinsic capacity of this tissue for self-healing. Although various approaches are proposed for the regeneration of cartilage, its repair still represents an enormous challenge for orthopedic surgeons. The field of tissue engineering currently offers some of the most promising strategies for cartilage restoration, in which assorted biomaterials and cell-based therapies are combined to develop new therapeutic regimens for tissue replacement. The current study describes thein vitrobehavior of human adipose-derived mesenchymal stem cells (hADSCs) encapsulated within calcium/cobalt (Ca/Co) alginate beads. These novel chondrogenesis-promoting scaffolds take advantage of the synergy between the alginate matrix and Co+2ions, without employing costly growth factors (e.g., transforming growth factor betas (TGF-βs) or bone morphogenetic proteins (BMPs)) to direct hADSC differentiation into cartilage-producing chondrocytes.

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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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