Y L Cao

University of Massachusetts Medical School, Worcester, Massachusetts, United States

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Publications (4)10.61 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: In the repair of cartilage defects, autologous tissue offers the advantage of lasting biocompatibility. The ability of bovine chondrocytes isolated from hyaline cartilage to generate tissue-engineered cartilage in a predetermined shape, such as a human ear, has been demonstrated; however, the potential of chondrocytes isolated from human elastic cartilage remains unknown. In this study, the authors examined the multiplication characteristics of human auricular chondrocytes and the ability of these cells to generate new elastic cartilage as a function of the length of time they are maintained in vitro. Human auricular cartilage, harvested from patients 5 to 17 years of age, was digested in collagenase, and the chondrocytes were isolated and cultured in vitro for up to 12 weeks. Cells were trypsinized, counted, and passaged every 2 weeks. Chondrocyte-polymer (polyglycolic acid) constructs were created at each passage and then implanted into athymic mice for 8 weeks. The ability of the cells to multiply in vitro and their ability to generate new cartilage as a function of the time they had been maintained in vitro were studied. A total of 31 experimental constructs from 12 patients were implanted and compared with a control group of constructs without chondrocytes. In parallel, a representative sample of cells was evaluated to determine the presence of collagen. The doubling rate of human auricular chondrocytes in vitro remained constant within the population studied. New tissue developed in 22 of 31 experimental implants. This tissue demonstrated the physical characteristics of auricular cartilage on gross inspection. Histologically, specimens exhibited dense cellularity and lacunae-containing cells embedded in a basophilic matrix. The specimens resembled immature cartilage and were partially devoid of the synthetic material of which the construct had been composed. Analyses for collagen, proteoglycans, and elastin were consistent with elastic cartilage. No cartilage was detected in the control implants. Human auricular chondrocytes multiply well in vitro and possess the ability to form new cartilage when seeded onto a three-dimensional scaffold. These growth characteristics might some day enable chondrocytes isolated from a small auricular biopsy to be expanded in vitro to generate a large, custom-shaped, autologous graft for clinical reconstruction of a cartilage defect, such as for congenital microtia.
    Plastic &amp Reconstructive Surgery 05/1999; 103(4):1111-9. · 3.54 Impact Factor
  • Y L Cao, C Ibarra, C Vacanti
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    ABSTRACT: Restoration of organ structure and function, utilizing tissue engineering technologies, often requires the use of a temporary porous scaffold. The function of the scaffold is to direct the growth of cells migrating from the surrounding tissue (tissue conduction), or of cells seeded within the porous structure of the scaffold. The scaffold must therefore provide a suitable substrate for cell attachment, differentiated function, and, in certain cases, cell proliferation (1-3). These critical requirements may be met by the choice of an appropriate material from which to construct the scaffold, although the suitability of the scaffold may also be affected by the processing technique. There are many biocompatible materials that could potentially be used to construct scaffolds, however, a biodegradable material is normally desirable, since the role of the scaffold is usually only a temporary one. Many natural and synthetic biodegradable polymers, such as collagen, poly(α-hydroxyesters), and poly(anhydrides), have been widely and successfully used as scaffolding materials because of their versatility and ease of processing. Many researchers have used poly(α-hydroxyesters) as starting materials from which to fabricate scaffolds, using a wide variety of processing techniques. These polymers have proven successful as temporary substrates for a number of cell types, allowing cell attachment, proliferation, and maintenance of differentiated function (10). Poly(α-hydroxyesters) such as the polyoxamers are a family of more than 30 different nontoxic, nonionic surface active agents. These compounds are made at elevated temperature and pressure by the sequential additi on of propylene oxide and then ethylene oxide to neutralize the salt that is generally retained in the final product.
    Methods in molecular medicine 01/1999; 18:75-83.
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    ABSTRACT: We describe a simple, effective approach to the creation of autologous tissue-engineered cartilage in the shape of a human nipple by injecting a reverse thermosensitive polymer seeded with autologous chondrocytes in an immunocompetent porcine animal model. A biodegradable, biocompatible copolymer of polyethylene oxide and polypropylene oxide (Pluronic F-127), which exists as a liquid below 4 degrees C and polymerizes to a thick gel when it is exposed to physiologic temperatures (body temperatures), was used as a vehicle for chondrocyte delivery and as a scaffold to guide growth. Autologous chondrocytes isolated from porcine auricular elastic cartilage and suspended in 30% (weight/volume) Pluronic F-127 were injected on the ventral surface of the pigs from which the cells had been isolated. A circumferential subdermal suture was used to support the contour of the implant and assist in its projection in the form of a human nipple. After 3 weeks, the skin over and surrounding the implant was tattooed to create the appearance of a human nipple-areolar complex. As controls, an equal number of injections were made using either cells alone (not suspended in hydrogel), or hydrogel alone. After 10 weeks, all specimens were excised and examined both grossly and histologically. Before harvesting, visual inspection of the tattooed chondrocyte-Pluronic F-127 hydrogel implant sites revealed that they closely resembled a human female nipple-areolar complex. Nodules were similar in size, shape, and texture to a human nipple at each injection site. Glistening opalescent tissue was surgically isolated from each implant site. Hematoxylin and eosin, safranine o, trichrome blue, and Verhoeff's stains of the experimental implants showed nodules with the characteristic histologic signs of elastic cartilage. Control injections of copolymer hydrogel alone exhibited no evidence of cartilage formation. Control injections of chondrocytes alone showed evidence of dissociated microscopic nodules of elastic cartilage.
    Plastic &amp Reconstructive Surgery 01/1999; 102(7):2293-8. · 3.54 Impact Factor
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    ABSTRACT: This study demonstrates that fibrin monomers can be polymerized into moldable gels and used for the encapsulation of isolated chondrocytes. This biologically derived scaffold will maintain three-dimensional spatial support, allowing new tissue development in a subcutaneous space. Chondrocytes isolated from the glenohumeral and humeroradioulnar joints of a calf were combined with cyroprecipitate and polymerized with bovine thrombin to create a fibrin glue gel with a final cell density of 12.5 x 10(6) cells/ml. The polymer-chondrocyte constructs were implanted subcutaneously in 12 nude mice and incubated for 6 and 12 weeks in vivo. Histologic and biochemical analysis including deoxyribonucleic acid (DNA) and glycosaminoglycan quantitation confirmed the presence of actively proliferating chondrocytes with production of a well-formed cartilaginous matrix in the transplanted samples. Control specimens from 12 implantation sites consisting of chondrocytes alone or fibrin glue substrates did not demonstrate any gross or histologic evidence of neocartilage formation. Moldable autogenous fibrin glue polymer systems have a potential to serve as alternatives to current proprietary polymer systems used for tissue engineering cartilage as well as autogenous grafts and alloplastic materials used for facial skeletal and soft-tissue augmentation.
    Plastic &amp Reconstructive Surgery 06/1998; 101(6):1580-5. · 3.54 Impact Factor

Publication Stats

240 Citations
10.61 Total Impact Points

Institutions

  • 1999
    • University of Massachusetts Medical School
      • Department of Anesthesiology
      Worcester, Massachusetts, United States