In Vitro Generation of Cartilage-Carrier-Constructs on Hydroxylapatite Ceramics with Different Surface Structures

Tissue engineering approaches for healing cartilage defects are partly limited by the inability to fix cartilage to bone during implantation. To overcome this problem, cartilage can be - already in vitro - generated on a ceramic carrier which serves as bone substitute. In this study, the influence of a hydroxylapatite carrier and its surface structure on the quality of tissue engineered cartilage was investigated. Application of the carrier reduced significantly biomechanical and biochemical properties of the generated tissue. In addition, slight changes in the quality of the formed matrix, in the adhesive strength between cartilage and biomaterial and in attachment and proliferation of a chondrocyte monolayer could be observed for commercial grade carriers, with respect to modified topographies obtained by smooth grinding/polishing. These first results demonstrated an influence of the carrier and its surface structure, but further research is needed for explaining the described effects and for optimization of cartilage-carrier-constructs

Improving In Vitro Generated Cartilage-Carrier-Constructs by Optimizing Growth Factor Combination

The presented study is focused on the generation of osteochondral implants for cartilage repair, which consist of bone substitutes covered with in vitro engineered cartilage. Re-differentiation of expanded porcine cells was performed in alginate gel followed by cartilage formation in high-density cell cultures. In this work, different combinations of growth factors for the stimulation of re-differentiation and cartilage formation have been tested to improve the quality of osteochondral implants. It has been demonstrated that supplementation of the medium with growth factors has significant effects on the properties of the matrix. The addition of the growth factors IGF-I (100 ng/mL) and TGF-β1 (10 ng/mL) during the alginate culture and the absence of any growth factors during the high-density cell culture led to significantly higher GAG to DNA ratios and Young’s Moduli of the constructs compared to other combinations. The histological sections showed homogenous tissue and intensive staining for collagen type II

Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques

HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Thus, some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses

The development of the collagen fibre network in tissue-engineered cartilage constructs in vivo : engineered cartilage reorganises fibre network

For long term durability of tissue-engineered cartilage implanted in vivo, the development of the collagen fibre network orientation is essential as well as the distribution of collagen, since expanded chondrocytes are known to synthesise collagen type I. Typically, these properties differ strongly between native and tissue-engineered cartilage. Nonetheless, the clinical results of a pilot study with implanted tissue-engineered cartilage in pigs were surprisingly good. The purpose of this study was therefore to analyse if the structure and composition of the artificial cartilage tissue changes in the first 52 weeks after implantation. Thus, collagen network orientation and collagen type distribution in tissue-engineered cartilage-carrier-constructs implanted in the knee joints of Göttinger minipigs for 2, 26 or 52 weeks have been further investigated by processing digitised microscopy images of histological sections. The comparison to native cartilage demonstrated that fibre orientation over the cartilage depth has a clear tendency towards native cartilage with increasing time of implantation. After 2 weeks, the collagen fibres of the superficial zone were oriented parallel to the articular surface with little anisotropy present in the middle and deep zones. Overall, fibre orientation and collagen distribution within the implants were less homogenous than in native cartilage tissue. Despite a relatively low number of specimens, the consistent observation of a continuous approximation to native tissue is very promising and suggests that it may not be necessary to engineer the perfect tissue for implantation but rather to provide an intermediate solution to help the body to heal itself