Approximately 5 million coronary stents are implanted world-wide each year. Most clinical stents are made of anti-corrosion metals such as stainless steels. Life-long presence of these stents, however, often falls short in preventing complications including in-stent restenosis (i.e. re-narrowing of arteries) and late thrombosis (i.e. clotting). Alternatives (e.g. biodegradable materials) that could deliver the life-long treatment for coronary blockade have long been sought. Here, a novel bioresorbable zinc (Zn)-strontium (Sr) alloy is proposed as a promising candidate for stent. Strong preliminary results demonstrated the potential and feasibility of this proposed study. It is believed that the Zn-based stent implants will eliminate the need for secondary surgeries and avoid many complications associated with current permanent implants. In addition, compared with other degradable stent materials, i.e., polymers or magnesium (Mg), tailored Zn alloys with right configuration offer stronger strength and ductility, slower degradation matching the pace of tissue healing, non-hydrogen evolution and better biocompatibility. Zn itself is an essential element for health while alloying element Sr is a nutrition element as well and can significantly enhance the mechanical and corrosion properties. The goals of this project are to determine the most effective compositions of novel binary Zn-Sr alloys and test their effectiveness as a coronary stent material, both in vitro and in vivo, in three specific aims.
Aim 1 : Prepare surface modified Zn- Sr binary alloys to tailor the material properties to accepted values of tensile strength, elongation to failure, and corrosion rate as stent implants. Implants are prepared by melting, rolling and extruding, and their microstructure, physical and mechanical properties are studied using electron microscopy, X-ray diffractometory, atomic emission spectrometry, tensile and uniaxial compression tests, immersion tests, and electrochemical tests, etc.
Aim 2 : Evaluate the biocompatibility of implants in vitro systematically. Implants will be examined on protein absorption, hemocompatibility, primary vascular cell viability and growth, vascular stem cell growth and differentiation, and direct endothelialization using in vitro cellular models.
Aim 3 : Evaluate implants corrosion, safety and interactions with vascular tissues in vivo using a rat arterial implantation model. Wire samples will be used to mimic the stent struts and their in vivo performances will be examined in a rat vascular model. Doppler ultrasound and microCT will be used to monitor the in vivo corrosion process, and histological examination will be performed to assess the inflammation and immune response.
This study will identify a new generation of biodegradable Zn-based stent materials which exhibit sufficient mechanical strength, fully-biodegradability at a rate matching the healing process, and good biocompatibility and revascularization. In a long term, it will positively influence the field of stent design, surface engineering, controlled degradation pace, and systematic in vitro and in vivo methodologies for assessments of medical implants. This novel biodegradable Zn-based stent implant would also provide a better recovery experience for patients as well as the quality of their lives because it may eliminate second surgery and long-term complications.
