The potential of tissue engineering in orthopedics

Landis, William J.; Jacquet, Robin; Hillyer, Jennifer; Zhang, Jean; Siperko, Lorraine M.; Chubinskaya, Susan; Asamura, Shinichi; Isogai, Noritaka

doi:10.1016/j.ocl.2004.06.006

Cited by 27 publications

(21 citation statements)

References 15 publications

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“…8 Tissue engineering and gene therapy concepts may improve cartilage repair by introducing repair cells, scaffolds, growth factors and other potential modulators of the osteochondral wound bed. [9][10][11] Owing to the limited repair potential of mature differentiated chondrocytes, there has been a strong interest in using mesenchymal stem cells for cartilage tissue engineering. 1,[12][13][14] Bone marrow cells are routinely accessed clinically for cartilage repair and form the basis for the repair of osteochondral injuries.…”

Section: Introductionmentioning

confidence: 99%

Adeno-associated viral gene transfer of transforming growth factor-β1 to human mesenchymal stem cells improves cartilage repair

et al. 2007

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Bone marrow cells are routinely accessed clinically for cartilage repair. This study was performed to determine whether adeno-associated virus (AAV) effectively transduces human bone marrow-derived mesenchymal stem cells (hMSC) in vitro, whether AAV infection interferes with hMSC chondrogenesis and whether AAV-transforming growth factor-beta-1 (TGF-b1)-transduced hMSC can improve cartilage repair in vivo. Adult hMSC were transduced with AAVgreen fluorescent protein (GFP) or AAV-transforming growth factor b1 (TGFb1) and studied in pellet cultures. For in vivo studies, AAV-GFP and AAV-TGF-b1-transduced hMSCs were implanted into osteochondral defects of 21 athymic rats. GFP was detected using fluorescent microscopy.Cartilage repair was assessed using gross and histological analysis at 4, 8 and 12 weeks. In pellet culture, GFP expression was visualized in situ through 21 days in vitro. In vivo GFP transgene expression was observed by in situ fluorescent surface imaging in 100% of GFP implanted defects at 2 , 67% at 8 and 17% at 12 weeks. Improved cartilage repair was observed in osteochondral defects implanted with AAV-TGF-b1-transduced hMSC at 12 weeks (P ¼ 0.0047). These results show that AAV is a suitable vector for gene delivery to improve the cartilage repair potential of human mesenchymal stem cells.

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Section: Introductionmentioning

confidence: 99%

Adeno-associated viral gene transfer of transforming growth factor-β1 to human mesenchymal stem cells improves cartilage repair

et al. 2007

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“…A tissue-engineered bone replacement would address these problems. [2][3][4] Successful engineering of bone tissue in vitro requires a strategy capable of inducing and promoting matrix production and mineralization with respect to 3-dimensional (3D) structures. 5,6 When developing an engineered orthopedic device, great care must be taken when selecting a repair material with the required mechanical integrity of a loadbearing tissue.…”

Section: Introductionmentioning

confidence: 99%

Using Dihydropyridine-Release Strategies to Enhance Load Effects in Engineered Human Bone Constructs

et al. 2006

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We report on the development of a novel biodegradable scaffold capable of enhancing mechanical signals for tissue-engineering applications. It has been shown that mechanotransduction enhances bone formation in vitro and in vivo; in tissue-engineering applications, this phenomenon is exploited through the use of mechanical bioreactors to generate bone tissue. The dihydropyridine agonist Bay K8644 (Bay) acts to increase the opening time of mechanosensitive voltage-operated calcium channels (VOCCs), specifi- cally L-type VOCCs, which are known to play a fundamental role in the early mediation of mechanotransduction. We have produced porous 3-dimensional, Bay-encapsulated biodegradable poly(L-lactide) acid scaffolds using a solvent-casting and salt-leaching technique. The effects of the released Bay on osteoid production and mineralization in human bone cell-seeded constructs following incubation in a perfusion-compression bioreactor in vitro was investigated using Western blotting techniques and a calcium assay protocol developed in our lab. Our newly developed scaffolds act by slowly releasing the calcium channel agonist Bay K8644 as observed using ultraviolet spectroscopy, maintaining the open state of mechanosensitive VOCCs responding to load, which augments the load signal at sites of strain across the scaffold. Our results demonstrate that, in the presence of physiological loading regimes in vitro, release of Bay enhances collagen I protein production and osteoid calcification more than non-Bay control constructs do. Osteopontin and alpha2delta1 VOCC subunit protein levels were also higher as a result of perfusion-compression conditioning. These results indicate that Bay-encapsulated scaffolds can be used in the presence of load to enhance the production of load-bearing engineered tissue.

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“…For example, modified natural materials such as cross-linked type I collagen, human or bovine dura mater and small intestinal submucosa, and various biosynthetic polymers including polyglycolic acid, polylactic acid, and polypropylene have been used extensively for tissue engineering. 19,[55][56][57][58][59][60] These studies have been facilitated because these synthetic biodegradable polymers are biocompatible and commercially available. They can be fabricated into 3-dimensional scaffolds of variable structure and porosity with a correspondingly wide range of mechanical and degradation properties.…”

Section: Scaffoldsmentioning

confidence: 99%