Cartilage regeneration by bone marrow cells‐seeded scaffolds

Wegener, Bernd; Schrimpf, Florian M.; Bergschmidt, Philipp; Pietschmann, Mathias F.; Utzschneider, Sandra; Milz, Stefan; Jansson, Volkmar; Müller, Peter E.

doi:10.1002/jbm.a.32885

Cited by 18 publications

(17 citation statements)

References 21 publications

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“…4 Previous evidence proved that bone marrow clots (MC) on the surface of the microfracture lesions provide an optimal environment for cartilaginous tissue repair. 5,6 However, this technique results in a repaired tissue with lower mechanical strength. This tissue is easily worn by daily activities, causing symptoms to recur and necessitating a second repair.…”

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confidence: 99%

Chondrogenic Regeneration Using Bone Marrow Clots and a Porous Polycaprolactone-Hydroxyapatite Scaffold by Three-Dimensional Printing

Yao

Wei

Liu

et al. 2015

Tissue Engineering Part A

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Scaffolds play an important role in directing three-dimensional (3D) cartilage regeneration. Our recent study reported the potential advantages of bone marrow clots (MC) in promoting extracellular matrix (ECM) scaffold chondrogenic regeneration. The aim of this study is to build a new scaffold for MC, with improved characteristics in mechanics, shaping, and biodegradability, compared to our previous study. To address this issue, this study prepared a 3D porous polycaprolactone (PCL)-hydroxyapatite (HA) scaffold combined with MC (Group A), while the control group (Group B) utilized a bone marrow stem cell seeded PCL-HA scaffold. The results of in vitro cultures and in vivo implantation demonstrated that although an initial obstruction of nutrient exchange caused by large amounts of fibrin and erythrocytes led to a decrease in the ratio of live cells in Group A, these scaffolds also showed significant improvements in cell adhesion, proliferation, and chondrogenic differentiation with porous recanalization in the later culture, compared to Group B. After 4 weeks of in vivo implantation, Group A scaffolds have a superior performance in DNA content, Sox9 and RunX2 expression, cartilage lacuna-like cell and ECM accumulation, when compared to Group B. Furthermore, Group A scaffold size and mechanics were stable during in vitro and in vivo experiments, unlike the scaffolds in our previous study. Our results suggest that the combination with MC proved to be a highly efficient, reliable, and simple new method that improves the biological performance of 3D PCL-HA scaffold. The MC-PCL-HA scaffold is a candidate for future cartilage regeneration studies.Introduction D ue to the poor regenerative capacity of cartilage in vivo, articular cartilage defect is a great challenge in the field of orthopedic surgery.1 There are several cartilage repair techniques, including microfracture, joint irrigation or debridement, osteochondral grafting, and autologous chondrocyte implantation.2,3 As it is a simple, convenient, and relatively inexpensive choice, microfracture has become the preferred clinical treatment. 4 Previous evidence proved that bone marrow clots (MC) on the surface of the microfracture lesions provide an optimal environment for cartilaginous tissue repair. 5,6 However, this technique results in a repaired tissue with lower mechanical strength. This tissue is easily worn by daily activities, causing symptoms to recur and necessitating a second repair. 7,8 The poor mechanical strength, the instability of MC, and the loss of bone marrowderived mesenchymal stem cell (BMSCs) may be the main barriers to fibrocartilage repair by microfracture. 9 Although the detailed mechanisms by which MC fibrocartilage forms are not clear, the combination of MC chondrogenic differentiation and high-strength biodegradable scaffolds may provide an advanced approach to the repair and functional reconstruction of cartilage defects. 10,11The fundamental concept underlying tissue engineering is the combination of a scaffold with living cells and/o...

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confidence: 99%

Chondrogenic Regeneration Using Bone Marrow Clots and a Porous Polycaprolactone-Hydroxyapatite Scaffold by Three-Dimensional Printing

Yao

Wei

Liu

et al. 2015

Tissue Engineering Part A

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“…Most studies have focused on the biological factors, whereas only a few have evaluated the material and mechanical factors. Furthermore, there have been few studies on the combined stimulation of the aforesaid factors . To the best of our knowledge, this study is the first report demonstrating that LIUS, a mechanical stimulation, cooperates with a potent biomaterial scaffold (i.e., the fibrin‐HA hydrogel used in this study) on the chondrogenesis of MSCs, whereas TGF‐β3, a well‐known chondrogenic inducer, does not.…”

Section: Discussionmentioning

confidence: 79%

“…The chondrogenic differentiation of MSCs is also influenced by scaffold biomaterials that provide the 3‐D culture environment . The scaffold biomaterials are thought to provide not only a physical platform in which the cells reside, but also a functional microenvironment that can affect the physiology and activity of the cells .…”

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confidence: 99%

Mechanical Stimulation by Ultrasound Enhances Chondrogenic Differentiation of Mesenchymal Stem Cells in a Fibrin-Hyaluronic Acid Hydrogel

Choi

Park

et al. 2013

Artificial Organs

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Chondrogenic differentiation and cartilage tissue formation derived from stem cells are highly dependent on both biological and mechanical factors. This study investigated whether or not fibrin-hyaluronic acid (HA) coupled with low-intensity ultrasound (LIUS), a mechanical stimulation, produces an additive or synergistic effect on the chondrogenesis of rabbit mesenchymal stem cells (MSCs) derived from bone marrow. For the purpose of comparison, rabbit MSCs were first cultured in fibrin-HA or alginate hydrogels, and then subjected to chondrogenic differentiation in chondrogenic-defined medium for 4 weeks in the presence of either transforming growth factor-beta3 (TGF-β3) (10 ng/mL) or LIUS treatment (1.0 MHz and 200 mW/cm(2) ). The resulting samples were evaluated at 1 and 4 weeks by histological observation, chemical assays, and mechanical analysis. The fibrin-HA hydrogel was found to be more efficient than alginate in promoting chondrogenesis of the MSCs by producing a larger amount of sulfated glycosaminoglycans (GAGs) and collagen, and engineered constructs made with the hydrogel demonstrated higher mechanical strength. At 4 weeks of tissue culture, the chondrogenesis of the MSCs in fibrin-HA were shown to be further enhanced by treatment with LIUS, as observed by analyses for the amounts of GAGs and collagen, and mechanical strength testing. In contrast, TGF-β3, a well-known chondrogenic inducer, showed a marginal additive effect in the amount of collagen only. These results revealed that LIUS further enhanced chondrogenesis of the MSCs cultured in fibrin-HA, in vitro, and suggested that the combination of fibrin-HA and LIUS is a useful tool in constructing high-quality cartilage tissues from MSCs.

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“…Eyrich et al demonstrated the capacity to form cartilage with chondrocyte-seeded stable fibrin gels (Eyrich et al, 2007). Wegener et al used polyester scaffolds filled with a fibrin gel (with or without chondrocytes) to repair cartilage defects in the femoral condyle in sheep (Wegener et al, 2010). This study confirmed cartilage formation and improved O'Driscoll scores in defects filled with these scaffolds.…”

Section: Fibrinmentioning

confidence: 77%