This proposal is directed at enhancing and maintaining fixation of total knee replacement (TKR) implants to the skeleton through a process known as bone ingrowth. In 1992, 199,000 primary total knee replacements were performed in the U.S. Of these, it has been estimated that 47% are """"""""cementless,"""""""" a type of implant in which fixation depends upon bone ingrowth into a porous surface. Two conditions known to inhibit initial fixation by bone ingrowth, lack of uniform contact between the implant and supporting bone and motion at the bone-implant interface, are inevitably present to some degree in cementless TKR. Recently, we have found (i) that transforming growth factor-beta/1 (TGF-beta/1), a known stimulator of bone repair, enhances bone ingrowth in a non-weight-bearing model and (ii) that bone morphogenetic protein-2 (BMP-2) retains its osteoinductive properties when applied to a porous-coated implant. TGF-beta enhances ongoing processes such as woven bone formation when delivered locally at freshly created sites of skeletal injury, whereas BMP works by inducing bone to form through a cartilaginous precursor. Thus, it is likely that TGF-beta will work well in situations where there is rigid fixation but gaps at the interface. However, the ability of TGF-beta to promote bone ingrowth in the presence of motion may be problematic. It seems likely that BMP would be a better means of promoting bone ingrowth in the presence of interface motion because of its different mechanism of action. Thus, the two hypotheses are directed at determining if treatment of the implant with either TGF-beta/1 or BMP-2 can enhance bone ingrowth and implant fixation in the presence of interface gaps and interface motion in a canine model of cementless TKR. Specifically, the dose-response curve for implants treated with each growth factor will be determined, followed by tests to assess the enhancing potential of these growth factors, using quantitative measures of implant fixation stability and bone ingrowth as the endpoints. The studies will help to determine in which situations application of growth factors to implants will be helpful for establishing fixation to the skeleton.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR042862-04
Application #
2517481
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Project Start
1994-09-30
Project End
1999-02-28
Budget Start
1997-09-01
Budget End
1999-02-28
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Rush University Medical Center
Department
Type
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60612
Sena, Kotaro; Sumner, Dale R; Virdi, Amarjit S (2010) Effect of recombinant human transforming growth factor-beta2 dose on bone formation in rat femur titanium implant model. J Biomed Mater Res A 92:1210-7
Barber, Thomas A; Ho, James E; De Ranieri, Aladino et al. (2007) Peri-implant bone formation and implant integration strength of peptide-modified p(AAM-co-EG/AAC) interpenetrating polymer network-coated titanium implants. J Biomed Mater Res A 80:306-20
Sumner, D R; Turner, T M; Urban, R M et al. (2006) Additive enhancement of implant fixation following combined treatment with rhTGF-beta2 and rhBMP-2 in a canine model. J Bone Joint Surg Am 88:806-17
De Ranieri, Aladino; Virdi, Amarjit S; Kuroda, Shinji et al. (2005) Local application of rhTGF-beta2 enhances peri-implant bone volume and bone-implant contact in a rat model. Bone 37:55-62
De Ranieri, Aladino; Virdi, Amarjit S; Kuroda, Shinji et al. (2005) Local application of rhTGF-beta2 modulates dynamic gene expression in a rat implant model. Bone 36:931-40
Kuroda, Shinji; Virdi, Amarjit S; Dai, Yang et al. (2005) Patterns and localization of gene expression during intramembranous bone regeneration in the rat femoral marrow ablation model. Calcif Tissue Int 77:212-25
De Ranieri, A; Virdi, A S; Kuroda, S et al. (2005) Saline irrigation does not affect bone formation or fixation strength of hydroxyapatite/tricalcium phosphate-coated implants in a rat model. J Biomed Mater Res B Appl Biomater 74:712-7
Broderick, E; Infanger, S; Turner, T M et al. (2005) Depressed bone mineralization following high dose TGF-beta1 application in an orthopedic implant model. Calcif Tissue Int 76:379-84
Kuroda, S; Virdi, A S; Li, P et al. (2004) A low-temperature biomimetic calcium phosphate surface enhances early implant fixation in a rat model. J Biomed Mater Res A 70:66-73
Sumner, D R; Turner, T M; Urban, R M et al. (2004) Locally delivered rhBMP-2 enhances bone ingrowth and gap healing in a canine model. J Orthop Res 22:58-65

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