Surface modified metal implants using doped hydroxyapatite

描述(由申请人提供)：骨骼缺乏的肌肉骨骼疾病，以及髋关节和膝盖问题等情况是当今存在的常见的重要人类健康状况。在这些情况下，重建通常伴随着必须与周围骨结合的人造金属植入物。这项赠款申请的目标是在钛(Ti)衬底上使用选定的掺杂剂和小分子进行羟基磷灰石(HA)涂层，以通过增强组织材料的相互作用来提高生物活性。这项研究的长期目标是通过设计成分分级的、小分子/离子掺杂的纳米涂层来开发新型HA涂层金属植入物，用于年轻患者和髋关节、肩部或膝关节植入物的翻修手术，由于增强了骨整合，提高了体内寿命。我们的设计目标是：1)通过可控的化学和微观结构提高界面的力学性能；2)提高生物活性，并在HA涂层的金属植入物中引入骨诱导活性。我们的初步数据表明，激光和射频感应等离子体处理钛表面的HA和磷酸三钙(另一种常用的钙磷酸盐相)涂层可以消除金属-陶瓷界面的离散和薄弱，提高涂层的界面强度。我们假设，优化的激光和等离子体工艺参数以及掺杂化学可以获得成分梯度的、界面牢固的HA涂层，以提高金属植入体涂层的机械稳定性。在目标1中，我们将研究它们的梯度微结构、物理和力学性能。我们将测试并比较我们的植入物与Biomet Inc.的商用涂层植入物，请参阅所附的支持信。根据我们的初步数据，我们发现所选择的掺杂剂可以促进大鼠早期骨组织的整合，并在体外控制人成骨细胞(OB)和破骨细胞(OC)的活性。由于硅可以诱导血管生成，锶和镁降低OC活性，镁和锌增强OB活性，我们推测掺杂剂的存在将调节体外生物相容性和体内骨组织整合。在目标2中，我们将评估掺杂HA涂层的钛样品，其界面机械强度为15 Mpa，符合当前的ASTM标准，在大鼠和兔的股骨远端造成髓内缺损。我们的初步数据表明，HA和TCP可用于负载和释放小分子药物和蛋白质，如阿伦磷酸(AD，一种双膦酸盐，BP，药物)/模型蛋白牛血清白蛋白(BSA)，AD的存在可以增加局部骨密度。我们的假设是，掺杂剂将改善早期骨细胞附着和体内组织与涂层的整合，而小分子药物，如阿仑膦酸盐，将局部增加 植入后的骨密度，特别是在翻修手术中。在目标3中，我们将在体外测定这些涂层的生物活性、掺杂剂/药物释放动力学，然后在体内研究这些涂层在大鼠股骨远端髓内缺损处的骨组织整合情况。通过该项目的科学理解，将改进非骨水泥关节置换和其他金属植入物的长期固定。

DESCRIPTION (provided by applicant): Musculoskeletal disorders with bone deficiencies, and conditions such as hip and knee problems are common important human health conditions that exist today. In these situations, reconstruction is often accompanied by an artificial metallic implant that must integrate with the surrounding bone. The objective of this grant application is focused on hydroxyapatite (HA) coating with selected dopants and small molecules on Titanium (Ti) substrates to improve bioactivity with enhanced tissue material interactions. The long-term goal of this research is to develop novel HA-coated metal implants by designing compositionally graded, small molecule / ionically doped nanoscale coatings for younger patients and revision surgeries in hip, shoulder or knee implants, with improved in vivo lifetime due to enhanced osseointegration. Our design goals are to: 1) enhanced interfacial mechanical properties via controlled chemistry and microstructure and 2) improve bioactivity and introduce osteoinductivity in HA-coated metal implants. Our preliminary data show that laser and RF induction plasma processed HA and tricalcium phosphate (TCP, another commonly used calcium phosphate phase) coating on Ti can eliminate discrete and weak metal- ceramic interface to improve interfacial strength of coatings. We hypothesize that optimized laser and plasma processing parameters along with dopant chemistry can produce a compositionally graded HA coating with strong interface to improve mechanical stability of coatings in vivo in metal implants. In Aim 1, we will study their gradient microstructure, physical and mechanical properties. We will test and compare our implants with commercially available coated implants from Biomet Inc., please see the attached support letter. Based on our preliminary data, we show that selected dopants can promote early-stage bone tissue integration in rat and control human osteoblast (OB) and osteoclast (OC) activities in vitro. Since Si can induce angiogenesis, Sr and Mg reduce OC activities, Mg and Zn enhance OB activities, we hypothesize that the presence of dopants will regulate in vitro biocompatibility as well as in vivo bone tissue integration. In Aim 2, we will evaluate doped HA coated Ti samples, with interfacial mechanical strength >15 MPa per current ASTM standard, creating an intramedullary defect in the distal femur in rat and rabbit models. Our preliminary data shows that HA and TCP can be used in loading and releasing small molecule drug and protein, e.g. alendronate (AD, a bisphosphonate, BP, drug) / model protein bovine serum albumin (BSA) and presence of AD can increase local bone density. Our hypothesis is that the dopants will improve early stage bone cell attachment and in vivo tissue integration with the coating while the small molecule drug, e.g. Alendronate, will locally increase bone density after implantation, especially in revision surgeries. In Aim 3, we will determine the bioactivity, dopant / drug release kinetics in vitro, followed by in vivo studies to evaluate bone tissue integration of these coatings using intramedullary defects in rat distal femurs. The scientific understanding from this program will lead to improved long-term fixation of cementless joint replacements and other metal implants.