Feasibility Study of a Novel Transapical Chordal Implantation System in a Porcine Model.

Transapical beating-heart mitral repair with chordal implantation system has been considered as an alternative treatment for degenerative mitral regurgitation. This study aimed to assess the feasibility and safety of the E-Chord system (Med-Zenith Medical, Beijing, China) for transapical beating-heart mitral valve repair in a porcine model. Artificial chordae were transapically implanted on the mitral valves of 12 anesthetized pigs under epicardial echocardiographic guidance and secured outside the left ventricular apex. The study endpoints included procedural success, device durability, and tissue response to the device. The procedural success rate was 100% (12/12). All animals were implanted with E-Chord in the anterior and posterior leaflets, respectively, and survived uneventfully until euthanized as planned. During the 180-day follow-up, no animal had significant mitral valve dysfunction. The gross observation showed no evidence of anchor detachment and chordal rupture, and there was no obvious damage or changes to mitral leaflets. Microscopic evaluation revealed that the endothelialization of anchor and chordae was completed 90 days after implantation and there was no evidence of chordal rupture, thrombosis, or infection during the 180-day follow-up. The E-Chord system was found to be feasible and safe for heart-beating mitral chordal implantation in a porcine model. The findings of this study suggest that the E-Chord system may be a potential alternative for the treatment of degenerative mitral regurgitation in humans.

In vitro and in vivo degradability and cytocompatibility of poly(l-lactic acid) scaffold fabricated by a gelatin particle leaching method.

Porous poly(l-lactic acid) (PLLA) scaffolds fabricated by a gelatin particle-leaching technique have good mechanical property and cytocompatibility, as demonstrated by a previous in vitro study. Here we investigate further the in vitro degradation of the scaffolds in terms of weight loss, water uptake, weight-average molecular weight, thermal behavior and morphology during a 39 week period in phosphate-buffered saline. The water uptake decreased dramatically during the initial stage due to release of the remaining gelatin, and then increased slightly with degradation time. The weight-average molecular weight decreased linearly as a function of time, while the crystallinity steadily increased with slightly decreased melting temperature. After degradation, many defects and big holes were seen in the scaffolds by scanning electron microscopy. Cartilage regeneration and scaffold disappearance in vivo were compared by implanting the construct into nude mice for 30-120 days. While the scaffolds maintained their intact pore structure after 23 weeks of degradation in vitro, they almost disappeared in vivo at the same time, implying a faster degradation rate in vivo. By 120 days after implantation, the scaffolds were hardly seen in the newly formed cartilage-like tissue. The regenerated cartilages could not maintain their predesigned shape after a long period of in vivo culture due to the weakening of the mechanical strength of the constructs as a result of PLLA degradation. The regions occupied initially by PLLA scaffold were filled later by collagen type II secreted by the chondrocytes, but with no evident basophilic proteoglycan.

Hydrogel-filled polylactide porous scaffolds for cartilage tissue engineering.

Polymer porous scaffolds and hydrogels have been separately employed as analogues of the native extra-cellular matrix (ECM). However, both of these two kinds of materials have their own advantages and shortcomings. In this work, an attempt to combine the advantages of these two kinds of materials is carried out. Poly-L-lactide (PLLA) scaffolds with good mechanical properties were prepared by thermally induced phase separation, which were then filled with hydrogel aiming at entrapment of cells within a support of predefined shape. Agar, which has a function to promote chondrogenesis, was selected to entrap chondrocytes, acting as analogues of native ECM. A straight forward merit of this construct is that both mechanical strength and macroscopic shape, and analogous ECM can be simultaneously achieved. The morphology and distribution of the chondrocytes were studied by confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). The cell growth behaviors were determined by MTT assay and collagen and glycosaminoglycan (GAG) secretion. After culture for 7 and 14 days, the cells in the construct were round and surrounded by the hydrogel. The MTT viability and the cell secretion in the chondrocytes/agar/scaffold construct were also higher than that of the chondrocytes/scaffold construct (control). Gelatin was further introduced into the construct, yielding improved GAG secretion and cytoviability. After implantation in the subcutaneous dorsum of nude mice for 4 weeks, cartilage-like specimens maintaining their original rectangular shapes were harvested. Histological examination showed that new cartilage was regenerated and a large quantity of collagen and GAG were secreted, while the cells in the control PLLA scaffold turned to be fibroblast-like with less secretion of extracellular matrices. The method provides a useful pathway of scaffold preparation and cell transplantation, which can achieve suitable mechanical properties and good cell performance simultaneously.

Poly(lactic acid) scaffold fabricated by gelatin particle leaching has good biocompatibility for chondrogenesis.

Three-dimensional poly(L-lactic acid) (PLLA) scaffolds with high porosity and an average pore size of 280-450 microm were fabricated using gelatin particles as porogen. The particles were bonded together by incubation in saturated water vapor at 70 degrees C for 3.5 h. After casting the PLLA/1,4-dioxane solution, freeze-drying and porogen leaching with 70 degrees C water, a porous scaffold with well-interconnected pores and some nano-fibers was obtained. The biological performance of the scaffold was evaluated by in vitro chondrocyte culture and in vivo implantation. In comparison with the control scaffold fabricated with NaCl particles as porogen under the same conditions, the experimental scaffold had better biological performance because the gelatin molecules were stably entrapped onto the pore surfaces. A larger number of cells in the experimental scaffold were observed by confocal laser scanning microscopy after the viable cells had been stained with fluorescein diacetate. The chondrocytes showed more spreading morphology. Higher cytoviability and secretion of glycosaminoglycan (GAG) were also determined in the experimental scaffold. After implantation of the chondrocytes/PLLA scaffold construct to the subcutaneous dorsum of nude mice for 30-120 days, cartilage-like specimens were harvested. Histological examination showed that the regenerated cartilages had a large quantity of collagen and GAG.