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.

Public Health Relevance

In many clinical situations reconstruction is often accompanied by an artificial metallic implant that must integrate with the surrounding bone. Bone loss due to trauma, aging, deep infection, tumor, irradiation, wear particles associated with periprosthetic osteolysis and other causes are challenging clinical scenarios. 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 scientific understanding from this program will lead to improved long-term fixation of cementless joint replacements, especially in revision surgeries where bone volume is compromised and for other metal implants.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
1R01AR066361-01A1
Application #
8789143
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Panagis, James S
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Washington State University
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
City
Pullman
State
WA
Country
United States
Zip Code
99164