Design and evaluation of a prosthetic anterior cruciate ligament replacement medical device

Rupture of the anterior cruciate ligament (ACL) is a relatively common sports-related injury for which the current treatment is reconstruction with an autograft or allograft. Drawbacks associated with each of the current options would make a prosthetic alternative advantageous, however, artificial ligaments are not widely used, having failed due to lack of biocompatibility and mechanical insufficiencies. To develop the next-generation prosthetic ACL, design control principles were applied including specification of comprehensive design inputs, risk analysis, and verification testing. A design was proposed utilizing polyvinyl alcohol and ultrahigh molecular weight polyethylene, selected for good biocompatibility and mechanical strength and stiffness suitable for ACL replacement. A biomimetic fibrous rope pattern was designed for the intra-articular ligament section of the prosthetic that produced a close match the static tensile behavior of the native ACL and which also demonstrated good resistance to fatigue and creep. A calcium phosphate coating was recommended for the sections of the device lying within the bone tunnel to increase the rate of osseointegration. The proposed design was then evaluated in a computational simulation to assess functional restoration and the effects of installation parameters such as tension and tunnel orientation on knee kinematics. The encouraging results of preclinical verification testing support further in vivo evaluation of the proposed design.PhDCommittee Chair: Ku, David; Committee Co-Chair: Cherkaoui, Mohammed; Committee Member: Cort, Laurent; Committee Member: Gleason, Rudolph; Committee Member: Guldberg, Rober

Design, analysis, testing, and evaluation of a prosthetic venous valve

Chronic Venous Insufficiency (CVI) is characterized by chronic venous hypertension from blood pooling in the lower limbs. The resulting symptoms include leg pain, varicose veins, fatigue, venous edema, skin pigmentation, inflammation, induration, and ulceration. Reflux from incompetent venous valves is a factor in up to 94% of individuals with CVI. Current treatments of CVI include compression stockings, drug therapy, vein disabling, venous stenting, and surgical correction with varying rates of success. However, a minimally invasive correction of deep venous reflux does not currently exist. A transcatheter prosthetic venous valve has the potential to be an effective, minimally invasive treatment for deep venous reflux which could treat up to 1.4 million individuals in the United States suffering from venous ulceration and make more than 1.7 billion dollars each year. Previously developed prosthetic venous valves have had problems with competency, patency, thrombogenicity, biocompatibility, and incorrect sizing. To meet the clinical need a prosthetic valve needs to be developed which succeeds where previous valves have failed. This thesis describes the design, analysis, pre-clinical testing, and evaluation of a novel prosthetic venous valve. Design specifications for an effective prosthetic venous valve were created. Verification tests were developed and performed which demonstrated that the valve met every design specification. Finite element and computational fluid dynamics simulations were performed to analyze the valve and calculated a maximum shear rate of 2300 s-1 in the valve during the high forward flow after a Valsalva maneuver. The valve is made of a biocompatible material that has low thrombogenicity, Poly(vinyl-alcohol) cryogel. On the average, the valve allows less than 0.5 mL/min of reflux at low and high retrograde pressures even after 500,000 cycles, indicating that it will reduce the reflux of individuals with venous reflux by more than 99.4%. The valve closes in less than 0.07 seconds and allows the distal pressure to rise to an average of 7% of the equilibrium pressure 30 seconds after a simulated ankle flexion. The valve increases the outflow resistance an average of 2.3 mmHg*min/L which is much less than obstruction levels,≥ 5 mmHg*min/L. The valve can fit in a 16 French catheter and is capable of percutaneous delivery. The base of the valve is 1.5 times the diameter of the vein in which it is to be implanted to help correct orientation upon deployment. Fluid behind the valve’s leaflets is ejected with a forward flow rate of 400 mL/min, suggesting that thrombus formation will not occur at this location. A stented valve remained patent in a porcine blood flow loop for 3 hours. The valve remains competent without buckling in a constricted vein at rest. The valve can expand to fit a vein with a maximum diameter 1.4 times the valve's initial diameter with low risk of tearing or leaflet prolapse. An IACUC protocol for a 12 week study to test the valve in sheep was prepared and approved. A study to evaluate the valve in humans is proposed with endpoints that can be tested for statistical significance and compared with other treatments for CVI. A set of valves which will correct reflux in the majority of common femoral, femoral, and popliteal deep veins is proposed and a sizing guide for surgeons is provided. The minimum distance between prosthetic valves placed in the same vein segment is 13 cm. A comparison of this valve with previously developed prosthetic venous valves and recommendations for work to be performed in the future are given. The valve proposed in this work is the only valve to meet all design specification for an effective prosthetic venous valve, and therefore shows great potential to be a minimally invasive treatment for deep venous reflux.M.S