Safety and efficacy of nano lamellar TiN coatings on nitinol atrial septal defect occluders in vivo.

Atrial septal defect (ASD) occlusion devices made of nickel-titanium (NiTi) have a major shortcoming in that they release nickel into the body. We modified NiTi occluders using Arc Ion Plating technology. Nano lamellar titanium-nitrogen (TiN) coatings were formed on the surfaces of the occluders. The safety and efficacy of the modified NiTi occluders were evaluated in animal model. The results showed that 38 out of 39 rams (97%) survived at the end of the experiment. Fibrous capsules formed on the surfaces of the devices. Gradual endothelialization took place through the attachment of endothelial progenitor cells from the blood and the migration of endothelial cells from adjacent endocardium. The neo-endocardium formed more quickly in the coated group than in the uncoated group, as indicated by the evaluation of the six month study group. After TiN coating, there was no significant difference in endothelial cell cycle. TiN coating significantly reduced the release of nickel in both in vivo and in vitro indicating an improved biocompatibility of the nitinol ASD occluders. Superior and modified ASD occluders may provide a good choice for people with nickel allergies after sFDA registration, which is expected in one to two years.

Human peripheral nerve-derived scaffold for tissue-engineered nerve grafts: histology and biocompatibility analysis.

Human acellular nerve grafts (ANGs) have been rarely used to construct tissue-engineered nerves compared to the animal-derived ANGs, and their potential clinical applications were relatively unknown. In this study, it was aimed to investigate the structure and components of a scaffold derived from human peripheral nerve and evaluate its biocompatibility. The human peripheral nerves were processed to prepare the scaffolds by chemical extraction. Light and electron microscopy were carried out to analyze scaffold structure and components. The analysis of cytotoxicity, hemolysis, and skin sensitization were performed to evaluate their biocompatibility. It was shown that Schwann cells and axons, identified by S-100 and neurofilament (NF) expression, were absent, and the scaffolds were cell-free and rich in collagen-I and laminin whose microarchitecture was similar to the fibrous framework of human peripheral nerves. It was revealed from biocompatibility tests that the scaffolds had very mild cytotoxicity and hemolysis, whereas skin sensitization was not observed. The constructed human peripheral nerve-derived scaffolds with well biocompatibility for clinical practice, which were cell-free and possess the microstructure and extracellular matrix (ECM) of a human nerve, might be an optimal scaffold for tissue-engineered nerve grafts in human.

Repairing large radial nerve defects by acellular nerve allografts seeded with autologous bone marrow stromal cells in a monkey model.

In this study, we aimed to evaluate the potential of tissue-engineered nerve grafts created from acellular allogenic nerve tissues combined with autologous bone marrow stromal cells (BMSCs) for repairing large peripheral nerve lesions. In a rhesus monkey model, a 2.5-cm-long gap was created in the radial nerve, followed by implantation of either autografts or acellular allografts seeded with autologous BMSCs, Schwann cells (SCs), or no cells. Five months after surgery nerve regeneration was assessed functionally, electrophysiologically, and histomorphometrically. Compared to non-cell-laden allografts, BMSC-laden allografts remarkably facilitated the recovery of the grasping functions of the animals. This functional improvement was coupled with increased nerve conduction velocities and peak amplitudes of compound motor action potentials, and greater axon growth, as well as higher target muscle weight. Moreover, the intensities of nerve regeneration in the BMSC-laden group were comparable to those achieved with SC-laden allografts and autografts. Our data highlight the potential of BMSC-seed allografts for the repair of long peripheral nerve lesions, and reveal comparable regeneration intensities achieved by BMSC-, and SC-laden allografts, as well as autografts. Given their wide availability, BMSCs may represent a promising cell source for tissue-engineered nerve grafts.

In vitro study of endothelial cells lining vascular grafts grown within the recipient's peritoneal cavity.

A living-tissue conduit with strong mechanical properties was used to produce small-diameter vessels. To improve blood compatibility, a shear-resistant confluent monolayer endothelium was formed on the luminal surface of the conduit. Under mechanical stimulation induced by pulsatile flow in a bioreactor, abrupt high-flow shear stress of 15.3 +/- 4.6 dynes/cm2 was applied to endothelial cells (ECs) seeded onto the lumen of a living-tissue conduit after 2 days of static culture. Scanning electron microscopy images revealed that most of the ECs were washed off after 3 days of dynamic culture. When shear stress was increased stepwise from 1.5 +/- 0.8 to 15.3 +/- 4.6 dynes/cm2 and applied to the ECs, scanning electron microscopy images of the luminal surface revealed that the confluent monolayer ECs were highly elongated and oriented to the flow direction, similar to findings in natural arteries in vivo. The results indicated that in vitro flow conditions played a key role in determining the durability of the EC layer. Careful design of the bioreactor and careful selection of the culture conditions will greatly improve the chances of producing a useful anti-thrombogenic surface for tissue-engineered small-diameter vessels.

[Supervision, administration and standard research related to tissue engineered medical products].

Tissue engineering advance in supplying the reparative and reconstructive medicine with promising tissue engineered medical products(TEMPs) and the new therapy alternative. The related supervision and administration of TEMPs is being developed and the standard research of TEMPs is also in progress. The Food and Drug Administration(FDA) of the United States has treated TEMPs as combined products and supervised them according to the level of risk to patients. Lately, FDA has determined that the Center for Devices and Radiological Health (CDRH) should take charge of examination and approval of TEMPs, with the cooperation of the Center for Biological Evaluations and Research(CBER). The regulatory controls have been established respectively in European Union and Japan. In China, TEMPs are identified as medical devices combined with cells. The Department of Medical Device of the State Food and Drug Administration (SFDA) is responsible for the examination and approval of TEMPs, and National Institute for the Control of Pharmaceutical & Biological Products(NICPBP) is responsible for evaluation tests. The standards of TEMPs are formulated mainly by the American Society of Testing Materials(ASTM) and International Standardization Organization(ISO).