Our long-term goal is to improve the clinical success of revision joint replacements. In our original application, we developed an experimental model of the revision implant setting. The model uses our established weight-loaded micromotion device, to engender a revision cavity with a tissue morphology representing an aseptically loosened human implant. At revision surgery, the pistoning PMMA implant is replaced with a prescribed implant/graft treatment. In our earlier work, we identified diminished osteogenic performance as a major deficit of revision implants, and we identified the relatively impermeable sclerotic bone (SB) rim that forms during the process of aseptic loosening as a major factor in this poorer fixation. We focus on this devitalized sclerotic bone rim since fixation in the sclerotic region is known to be critical clinically for achieving overall stability of a revision implant. We have successfully shown that cracking (perforating) the sclerotic bone rim improved revision fixation 5-7 fold. Addition of bone graft increased fixation up to 40 fold, and, with rim cracking, hydroxyapatite (HA) implants had superior fixation to their titanium (Ti) counterparts. Graft improved fixation in all settings investigated. We will study hypotheses addressing three Aims, based on promising results from the prior funding period.
Aim 1 : to provide greater access (of native growth factors, cells, marrow) to the revision interface by perforating (cracking) the sclerotic bone rim. We will compare rim cracking to the procedure of reaming to remove the SB rim.
Aim 2 : to improve utilization of native growth factors and cells by coatings encouraging bone growth directly on the revision implant surface.
Aim 3 : to augment the revision interface with local application of bone graft and bone graft substitutes, with and without bone marrow aspirate and platelet rich plasma (PRP) concentrates.
For Aim 1, the two access techniques studied are rim cracking and reaming.
For Aim 2, the three revision implant coatings studied are Ti, HA + RGD and Poly, D, Lactide (PLDDA) (with TGFb1 and IGF1).
For Aim 3, the four augmentations studied are allograft, coralline hydroxyapatite, with and without marrow aspirate and PRP. Sixteen paired groups of these treatments will determine effectiveness, interactions and synergies of treatments. Outcome measures are histomorphometric (% bone area and implant contact in zones, and connectivity) micro-CT (including bone volume, surface to volume ratio, anisotropy index), and mechanical (static pushout strength, stiffness, energy, and dynamic damping factor and damping odulus). Our active partnership of an accomplished clinician scientist and his team, and bioengineers and scientists bring a diverse set of competencies working towards our common goal. Our good collaborations and established and clinically verified experimental model is a strong base for future studies to improve the longevity of clinically vexing revision implants.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Skeletal Biology Structure and Regeneration Study Section (SBSR)
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Panagis, James S
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Minneapolis Medical Research Fdn, Inc.
United States
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Baas, Jorgen; Vestermark, Marianne; Jensen, Thomas et al. (2017) Topical bisphosphonate augments fixation of bone-grafted hydroxyapatite coated implants, BMP-2 causes resorption-based decrease in bone. Bone 97:76-82
Jakobsen, Thomas; Bechtold, Joan E; Søballe, Kjeld et al. (2017) Local delivery of zoledronate from a poly (d,l-lactide)-coating increases fixation of hydroxy-coated implants. J Orthop Res 35:974-979
Jakobsen, Thomas; Bechtold, Joan E; Søballe, Kjeld et al. (2016) Local delivery of zoledronate from a poly (D,L-lactide)-Coating increases fixation of press-fit implants. J Orthop Res 34:65-71
Bechtold, Joan E; Swider, Pascal; Goreham-Voss, Curtis et al. (2016) Experimental and Numerical Models of Complex Clinical Scenarios; Strategies to Improve Relevance and Reproducibility of Joint Replacement Research. J Biomech Eng 138:021008
Hermansen, Lars L; Sørensen, Mette; Barckman, Jeppe et al. (2015) Incorporation of raloxifene-impregnated allograft around orthopedic titanium implants impairs early fixation but improves new bone formation. Acta Orthop 86:127-33
Barckman, Jeppe; Baas, Jorgen; Sorensen, Mette et al. (2014) Does tobramycin impregnation of allograft bone affect implant fixation? - an experimental study in 12 dogs. J Biomed Mater Res B Appl Biomater 102:173-80
Barckman, Jeppe; Baas, Jorgen; Sørensen, Mette et al. (2013) Periosteal augmentation of allograft bone and its effect on implant fixation - an experimental study on 12 dogs(). Open Orthop J 7:18-24
Barckman, Jeppe; Baas, Jorgen; Sorensen, Mette et al. (2013) Rinsing of allograft bone does not improve implant fixation: a study in 12 dogs. Acta Orthop 84:307-13
Zainali, Kasra; Danscher, Gorm; Jakobsen, Thomas et al. (2013) Assessment of modified gold surfaced titanium implants on skeletal fixation. J Biomed Mater Res A 101:195-202
Sørensen, Mette; Barckman, Jeppe; Bechtold, Joan E et al. (2013) Preclinical evaluation of zoledronate to maintain bone allograft and improve implant fixation in revision joint replacement. J Bone Joint Surg Am 95:1862-8

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