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

2013 ◽  
Vol 1498 ◽  
pp. 59-66 ◽  
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.

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

2013 ◽  
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.

TRENDS AND CHALLENGES OF CARTILAGE TISSUE ENGINEERING

2009 ◽  
Vol 21 (03) ◽  
pp. 149-155 ◽  
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.

scholarly journals Silencing Smad7 Potentiates BMP2-induced Chondrogenic Differentiation and Inhibits Endochondral Ossification in Human Synovial Derived Mesenchymal Stem Cells

2020 ◽  
Author(s):  
pengcheng xiao ◽  
Zhenglin Zhu ◽  
Chengcheng Du ◽  
Yongsheng Zeng ◽  
junyi Liao ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Chondrogenic Differentiation ◽  
Endochondral Ossification ◽  
Cartilage Tissue Engineering ◽  
Cartilage Tissue ◽  
Blue Staining ◽  
Alcian Blue Staining ◽  
Cartilage Injuries

Abstract Background: Cartilage injuries pose formidable challenges for effective clinical management. Autologous stem cell-based therapies and transgene-enhanced cartilage tissue engineering may open new avenues for the treatment of cartilage injuries. Bone morphogenetic protein 2 (BMP2) is a promising chondrogenic growth factors for transgene-enhanced cartilage tissue engineering. However the BMP2 is failed to maintain a stable chondrogenic phenotype as it also induces robust endochondral ossification. Recently, human synovial derived mesenchymal stem cells (hSMSCs) arouse interested through the poor differentiation potential into osteogenic lineage. Smad7, a protein to antagonizes TGF-β/BMP signaling pathway has been discovered significant in the endochondral ossification. In the present study ,we further explore the effect of downregulate Smad7 in BMP2-induced chondrogenic differentiation of hSMSCs. Methods: hSMSCs were isolated from synovium of human knee joint through adhesion growth. In vitro and in vivo chondrogenic differentiation models of hSMSCs were constructed . Transgenes of BMP2, silencing Smad7 and Smad7 were expressed by adenoviral vectors. The osteogenic differentiation was detected by alkaline phosphatase staining, alizarin red staining. The chondrogenic differentiation was detected by alcian blue staining. Gene expression was determined by reverse transcription and quantitative real-time PCR (RT-qPCR), Immunofluorescence and immunohistochemistry. The subcutaneous stem cell implantation model was established and evaluated by micro-CT , h＆e staining, alcian blue staining and immunohistochemistry assay.Results: Compared to other MSCs, hSMSCs performed less of capability to osteogenic differentiation. But the occurrence of endochondral ossification is still inevasible during BMP2 induced cartilage formation. We found that silencing Smad7 enhanced the BMP2-induced chondrogenic differentiation of hSMSCs in vitro. Also, it leading to much less of hypertrophic differentiation. The subcutaneous stem cells implantation assays demonstrated silencing Smad7 potentiates BMP2-induced cartilage formation and inhibits endochondral ossification. Conclusion: This study strongly suggests that application of hSMSCs , cell scaffolds and silencing Smad7 can potentiate BMP2-induced chondrogenic differentiation and inhibit endochondral ossification. Thus, inhibit the expression of Smad7 in BMP2-induced hSMSCs differentiation may be a new strategy for cartilage tissue engineering.

scholarly journals In vitro study of cartilage tissue engineering using human adipose-derived stem cells induced by platelet-rich plasma and cultured on silk fibroin scaffold

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Imam Rosadi ◽  
Karina Karina ◽  
Iis Rosliana ◽  
Siti Sobariah ◽  
Irsyah Afini ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mrna Expression ◽  
Silk Fibroin ◽  
Platelet Rich Plasma ◽  
Cartilage Tissue Engineering ◽  
Cartilage Tissue ◽  
Silk Fibroin Scaffold

Abstract Background Cartilage tissue engineering is a promising technique for repairing cartilage defect. Due to the limitation of cell number and proliferation, mesenchymal stem cells (MSCs) have been developed as a substitute to chondrocytes as a cartilage cell-source. This study aimed to develop cartilage tissue from human adipose-derived stem cells (ADSCs) cultured on a Bombyx mori silk fibroin scaffold and supplemented with 10% platelet-rich plasma (PRP). Methods Human ADSCs and PRP were characterized. A silk fibroin scaffold with 500 μm pore size was fabricated through salt leaching. ADSCs were then cultured on the scaffold (ADSC-SS) and supplemented with 10% PRP for 21 days to examine cell proliferation, chondrogenesis, osteogenesis, and surface marker expression. The messenger ribonucleic acid (mRNA) expression of type 2 collagen, aggrecan, and type 1 collagen was analysed. The presence of type 2 collagen confirming chondrogenesis was validated using immunocytochemistry. The negative and positive controls were ADSC-SS supplemented with 10% foetal bovine serum (FBS) and ADSC-SS supplemented with commercial chondrogenesis medium, respectively. Results Cells isolated from adipose tissue were characterized as ADSCs. Proliferation of the ADSC-SS PRP was significantly increased (p < 0.05) compared to that of controls. Chondrogenesis was observed in ADSC-SS PRP and was confirmed through the increase in glycosaminoglycans (GAG) and transforming growth factor-β1 (TGF-β1) secretion, the absence of mineral deposition, and increased surface marker proteins on chondrogenic progenitors. The mRNA expression of type 2 collagen in ADSC-SS PRP was significantly increased (p < 0.05) compared to that in the negative control on days 7 and 21; however, aggrecan was significantly increased on day 14 compared to the controls. ADSC-SS PRP showed stable mRNA expression of type 1 collagen up to 14 days and it was significantly decreased on day 21. Confocal analysis showed the presence of type 2 collagen in the ADSC-SS PRP and positive control groups, with high distribution outside the cells forming the extracellular matrix (ECM) on day 21. Conclusion Our study showed that ADSC-SS with supplemented 10% PRP medium can effectively support chondrogenesis of ADSCs in vitro and promising for further development as an alternative for cartilage tissue engineering in vivo.

Influence of Chondrocyte Zone on Co-Cultures With Mesenchymal Stem Cells in HA Hydrogels for Cartilage Tissue Engineering

2012 ◽  
Author(s):  
Minwook Kim ◽  
Jason A. Burdick ◽  
Robert L. Mauck
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hyaluronic Acid ◽  
Articular Chondrocytes ◽  
Cartilage Tissue Engineering ◽  
3D Culture ◽  
Cartilage Tissue ◽  
Cell Type

Mesenchymal stem cells (MSCs) are an attractive cell type for cartilage tissue engineering in that they can undergo chondrogenesis in a variety of 3D contexts [1]. Focused efforts in MSC-based cartilage tissue engineering have recently culminated in the formation of biologic materials possessing biochemical and functional mechanical properties that match that of the native tissue [2]. These approaches generally involve the continuous or intermittent application of pro-chondrogenic growth factors during in vitro culture. For example, in one recent study, we showed robust construct maturation in MSC-seeded hyaluronic acid (HA) hydrogels transiently exposed to high levels of TGF-β3 [3]. Despite the promise of this approach, MSCs are a multipotent cell type and retain a predilection towards hypertrophic phenotypic conversion (i.e., bone formation) when removed from a pro-chondrogenic environment (e.g., in vivo implantation). Indeed, even in a chondrogenic environment, many MSC-based cultures express pre-hypertrophic markers, including type X collagen, MMP13, and alkaline phosphatase [4]. To address this issue, recent studies have investigated co-culture of human articular chondrocytes and MSCs in both pellet and hydrogel environments. Chondrocytes appear to enhance the initial efficiency of MSC chondrogenic conversion, as well as limit hypertrophic changes in some instances (potentially via secretion of PTHrP and/or other factors) [5–7]. While these findings are intriguing, articular cartilage has a unique depth-dependent morphology including zonal differences in chondrocyte identity. Ng et al. showed that zonal chondrocytes seeded in a bi-layered agarose hydrogel construct can recreate depth-dependent cellular and mechanical heterogeneity, suggesting that these identities are retained with transfer to 3D culture systems [8]. Further, Cheng et al. showed that differences in matrix accumulation and hypertrophy in zonal chondrocytes was controlled by bone morphogenic protein [9]. To determine whether differences in zonal chondrocyte identity influences MSC fate decisions, we evaluated functional properties and phenotypic stability in photocrosslinked hyaluronic acid (HA) hydrogels using distinct, zonal chondrocyte cell fractions co-cultured with bone marrow derived MSCs.

scholarly journals Articular cartilage tissue engineering with stem cells implanted onto nanoscaffolds and platelet-rich plasma

2017 ◽  
Vol 3 (3) ◽  
pp. 322
Author(s):  
Hadeer A. Abbassy ◽  
Laila M. Montaser ◽  
Sherin M. Fawzy
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Articular Cartilage ◽  
Soft Tissues ◽  
Platelet Rich Plasma ◽  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Cartilage Defects ◽  
Great Promise

<p class="abstract">Musculoskeletal medicine targets both cartilage regeneration and healing of soft tissues. Articular cartilage repair and regeneration is primarily considered to be due to its poor regenerative properties. Cartilage defects due to joint injury, aging, or osteoarthritis have low self-repair ability thus they are most often irreversible as well as being a major cause of joint pain and chronic disability. Unfortunately, current methods do not seamlessly restore hyaline cartilage and may lead to the formation of fibro- or continue hypertrophic cartilage. Deficiency of efficient modalities of therapy has invited research to combine stem cells, scaffold materials and environmental factors through tissue engineering. Articular cartilage tissue engineering aims to repair, regenerate, and hence improve the function of injured or diseased cartilage. This holds great potential and has evoked intense interest in improving cartilage therapy. Platelet-rich plasma (PRP) and/or stem cells may be influential for tissue repair as well as cartilage regenerative processes.  A great promise to advance current cartilage therapies toward achieving a consistently successful modality has been held for addressing cartilage afflictions. The use of stem cells, novel biologically inspired scaffolds and, emerging nanotechnology may be the best way to reach this objective via tissue engineering. A current and emergent approach in the field of cartilage tissue engineering is explained in this review for specific application. In the future, the development of new strategies using stem cells seeded in scaffolds and the culture medium supplemented with growth factors could improve the quality of the newly formed cartilage<span lang="EN-IN">.</span></p>

scholarly journals Cartilage tissue engineering for craniofacial reconstruction

2020 ◽  
Vol 47 (5) ◽  
pp. 392-403 ◽  
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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