In situ tissue regeneration using a warp-knitted fabric in the canine aorta and inferior vena cava.

OBJECTIVES: Materials used in paediatric cardiac surgery have drawbacks of deterioration, calcification and pseudointimal proliferation resulting in haemodynamic disturbance. The aim of this study was to investigate whether these drawbacks can be overcome by in situ tissue regeneration using a newly developed synthetic hybrid fabric (SHF). METHODS: The SHF is an expandable, warp-knitted fabric composed of a combination of biodegradable [poly-l-lactic acid (PLLA)] and non-biodegradable (polyethylene terephthalate) yarns. The fabric is coated with cross-linked gelatin. Mechanical properties of the SHF were compared with those of 2 commercial products: expanded polytetrafluoroethylene sheet and glutaraldehyde-treated bovine pericardium. An oval-shaped defect created in the canine descending aorta or inferior vena cava was filled with the SHF patch. After 2 weeks and 1, 3, 6 and 12 (or 24 in the inferior vena cava) months, the patch was removed for histological examination and evaluation of the remaining PLLA. RESULTS: The SHF exhibited satisfactory tensile and suture retention strength for surgical implantation similar to or better than the 2 commercial products. Tissue regeneration was induced with multilayered smooth muscle cells and collagen fibres on both sides of the patch, along with a mature endothelial layer and tissue connections containing vasa vasorum across the patch in the aorta and inferior vena cava. Inflammatory reactions were minimal, and no calcium deposition occurred. The molecular weight of PLLA was reduced to half at 12 months after implantation. CONCLUSIONS: The SHF may solve the drawbacks of the existing products. Further studies of the expandability of the SHF patch after degradation of PLLA are warranted.

Essential role of Tip60-dependent recruitment of ribonucleotide reductase at DNA damage sites in DNA repair during G1 phase.

A balanced deoxyribonucleotide (dNTP) supply is essential for DNA repair. Here, we found that ribonucleotide reductase (RNR) subunits RRM1 and RRM2 accumulated very rapidly at damage sites. RRM1 bound physically to Tip60. Chromatin immunoprecipitation analyses of cells with an I-SceI cassette revealed that RRM1 bound to a damage site in a Tip60-dependent manner. Active RRM1 mutants lacking Tip60 binding failed to rescue an impaired DNA repair in RRM1-depleted G1-phase cells. Inhibition of RNR recruitment by an RRM1 C-terminal fragment sensitized cells to DNA damage. We propose that Tip60-dependent recruitment of RNR plays an essential role in dNTP supply for DNA repair.