OBJECTIVE : Tissue engineering of heart valves (TEHV) has largely focused on developing a complete replacement valve out of engineered tissue or synthetic biomaterials. However, several widely prevalent heart valve lesions, such as mitral, aortic and tricuspid regurgitation, have relatively preserved native valve structure with regurgitation emanating from a small gap between the leaflets during valve closure. In this study, we sought to develop a biomaterial covered miniature implant that can be attached to the native valve leaflet at the site of the regurgitation, which enables tissue ingrowth from the surrounding native valve tissue, and permanently extends the native leaflet to restore valve competence.

METHODS: Implant: The implant was made from a thin nitinol skeleton with a curvilinear shape upon attachment to the native leaflet ( Fig 1A-B ). The extending part was covered in a biomaterial to allow in situ tissue ingrowth. In vitro experiments: In a bench-top pig mitral valve model (n=5) of mitral regurgitation (MR), the efficacy of correcting severe MR was investigated. Mobility of the posterior leaflet, transmitral gradient and diastolic geometric orifice area were measured before and after the implant. In vivo experiments: Three pigs (n=3) were induced with MR and the implant was surgically deployed. MR was assessed before and after implant with serial echocardiography for 4-6 months after the implant.

RESULTS: Systolic images in the in-vitro model, depict a wide regurgitant orifice before implanting the device ( Fig 1C1 ), and complete closure of the orifice after extending the posterior leaflet with the device ( Fig 1C2 ). Regurgitation severity reduced from 3+ to zero with the implant. Diastolic regurgitant orifice area was 186.1 82.6 sq-mm before repair, with slight reduction to 158.5 85.4 sq-mm after implant. In the chronic swine, MR was reduced immediately after implantation ( Fig 1D1-2 ), with the implant-attached leaflet mobile( Fig 1E1-2 ). At termination, tissue ingrowth/ in situ tissue formation was clear ( Fig 1F ).

CONCLUSIONS: The implant can correct regurgitation by allowing in situ tissue formation that extends the native leaflet and covers the regurgitation orifice. Transcatheter delivery is in development.


Figure 1: (A) The posterior leaflet extending implant with an atrial and ventricular arm that can recoil towards each other ; (B) Suture less attachment of the implant to the posterior mitral leaflet in an explanted pig hea11, with the GoreTex covered extender region projecting from the surface into the mitral orifice; (Cl) A large regurgitant orifice mitral va lve in the in vitro pig va lve setup created by annular dilatation and papillary muscle displacement ; (C2) Complete correction of the regurgitant orifice by the extending segment of the implant attached to the posterior leaflet at the site of regurgitation ; (D1) Moderate FMR in a pig at 8 weeks after inferior myocardial infarction; (D2) complete correction of FMR after implanting the posterior leaflet extender; (El) 3D echo image of the mitral va lve at 120 days after implantation in a pig ; (E2) 3D echo image in the same pig in diastole , depicting a preserved diastolic orifice; (F) Complete encapsu lation of the device into the mitral leaflet on terminal necropsy.