This research review aims to focus attention on the effect of specific surgical and host factors on implant fixation, and the importance of accounting for them in experimental and numerical models. These factors affect (a) eventual clinical applicability and (b) reproducibility of findings across research groups. Proper function and longevity for orthopedic joint replacement implants relies on secure fixation to the surrounding bone. Technology and surgical technique has improved over the last 50 years, and robust ingrowth and decades of implant survival is now routinely achieved for healthy patients and first-time (primary) implantation. Second-time (revision) implantation presents with bone loss with interfacial bone gaps in areas vital for secure mechanical fixation. Patients with medical comorbidities such as infection, smoking, congestive heart failure, kidney disease, and diabetes have a diminished healing response, poorer implant fixation, and greater revision risk. It is these more difficult clinical scenarios that require research to evaluate more advanced treatment approaches. Such treatments can include osteogenic or antimicrobial implant coatings, allo- or autogenous cellular or tissue-based approaches, local and systemic drug delivery, surgical approaches. Regarding implant-related approaches, most experimental and numerical models do not generally impose conditions that represent mechanical instability at the implant interface, or recalcitrant healing. Many treatments will work well in forgiving settings, but fail in complex human settings with disease, bone loss, or previous surgery. Ethical considerations mandate that we justify and limit the number of animals tested, which restricts experimental permutations of treatments. Numerical models provide flexibility to evaluate multiple parameters and combinations, but generally need to employ simplifying assumptions. The objectives of this paper are to (a) to highlight the importance of mechanical, material, and surgical features to influence implant–bone healing, using a selection of results from two decades of coordinated experimental and numerical work and (b) discuss limitations of such models and the implications for research reproducibility. Focusing model conditions toward the clinical scenario to be studied, and limiting conclusions to the conditions of a particular model can increase clinical relevance and research reproducibility.

References

1.
Griffith
,
M. J.
,
Seidenstein
,
M. K.
,
Williams
,
D.
, and
Charnley
,
J.
,
1978
, “
Socket Wear in Charnley Low Friction Arthroplasty of the Hip
,”
Clin. Orthop. Relat. Res.
,
137
, pp.
37
47
.
2.
Charnley
,
J.
,
1961
, “
Arthroplasty of the Hip. A New Operation
,”
Lancet
,
277
(
7187
), pp.
1129
1132
.
3.
Lovald
,
S. T.
,
Ong
,
K. L.
,
Lau
,
E. C.
,
Schmier
,
J. K.
,
Bozic
,
K. J.
, and
Kurtz
,
S. M.
,
2014
, “
Mortality, Cost, and Downstream Disease of Total Hip Arthroplasty Patients in the Medicare Population
,”
J. Arthroplasty
,
29
(
1
), pp.
242
246
.
4.
Warth
,
L. C.
,
Callaghan
,
J. J.
,
Liu
,
S. S.
,
Klaassen
,
A. L.
,
Goetz
,
D. D.
, and
Johnston
,
R. C.
,
2014
, “
Thirty-Five-Year Results After Charnley Total Hip Arthroplasty in Patients Less Than Fifty Years Old. A Concise Follow-Up of Previous Reports
,”
J. Bone Joint Surg. Am.
,
96
(
21
), pp.
1814
1819
.
5.
Bozic
,
K. J.
,
Kamath
,
A. F.
,
Ong
,
K.
,
Lau
,
E.
,
Kurtz
,
S.
,
Chan
,
V.
,
Vail
,
T. P.
,
Rubash
,
H.
, and
Berry
,
D. J.
,
2015
, “
Comparative Epidemiology of Revision Arthroplasty: Failed THA Poses Greater Clinical and Economic Burdens Than Failed TKA
,”
Clin. Orthop. Relat. Res.
,
473
(
6
), pp.
2131
2138
.
6.
Bozic
,
K. J.
,
Kurtz
,
S. M.
,
Lau
,
E.
,
Ong
,
K.
,
Vail
,
T. P.
, and
Berry
,
D. J.
,
2009
, “
The Epidemiology of Revision Total Hip Arthroplasty in the United States
,”
J. Bone Joint Surg. Am.
,
91
(
1
), pp.
128
133
.
7.
Smith
,
M. A.
,
Deakin
,
A. H.
,
Allen
,
D.
, and
Baines
,
J.
, “
Midterm Outcomes of Revision Total Hip Arthroplasty Using a Modular Revision Hip System
,”
J. Arthroplasty
, epub.
8.
Bozic
,
K. J.
,
Lau
,
E.
,
Ong
,
K.
,
Chan
,
V.
,
Kurtz
,
S.
,
Vail
,
T. P.
,
Rubash
,
H. E.
, and
Berry
,
D. J.
,
2014
, “
Risk Factors for Early Revision After Primary Total Hip Arthroplasty in Medicare Patients
,”
Clin. Orthop. Relat. Res.
,
472
(
2
), pp.
449
454
.
9.
Ong
,
K. L.
,
Lau
,
E.
,
Suggs
,
J.
,
Kurtz
,
S. M.
, and
Manley
,
M. T.
,
2010
, “
Risk of Subsequent Revision After Primary and Revision Total Joint Arthroplasty
,”
Clin. Orthop. Relat. Res.
,
468
(
11
), pp.
3070
3076
.
10.
Syed
,
M. A.
,
Hutt
,
N. J.
,
Shah
,
N.
, and
Edge
,
A. J.
,
2015
, “
Hydroxyapatite Ceramic-Coated Femoral Components in Young Patients Followed Up for 17 to 25 Years: An Update of a Previous Report
,”
Bone Joint J.
,
97-B
(
6
), pp.
749
754
.
11.
Sandiford
,
N. A.
,
Skinner
,
J. A.
,
East
,
D. J.
,
Butler-Manuel
,
A.
,
Hinves
,
B. L.
, and
Shepperd
,
J. A.
,
2014
, “
Primary Total Hip Arthroplasty With Hydroxyapatite Coated Titanium Femoral Stems. Does Design Philosophy Influence Long Term Outcome?: Results of a Prospective Randomised Controlled Trial With Follow-Up of 10–15 Years
,”
Acta Orthop. Belg.
,
80
(
3
), pp.
372
379
.
12.
Parvizi
,
J.
,
Alijanipour
,
P.
,
Barberi
,
E. F.
,
Hickok
,
N. J.
,
Phillips
,
K. S.
,
Shapiro
,
I. M.
,
Schwarz
,
E. M.
,
Stevens
,
M. H.
,
Wang
,
Y.
, and
Shirtliff
,
M. E.
,
2015
, “
Novel Developments in the Prevention, Diagnosis, and Treatment of Periprosthetic Joint Infections
,”
J. Am. Acad. Orthop. Surg.
,
23
(
S
), pp.
S32
S43
.
13.
Solomon
,
L. B.
,
Costi
,
K.
,
Kosuge
,
D.
,
Cordier
,
T.
,
McGee
,
M. A.
, and
Howie
,
D. W.
,
2015
, “
Revision Total Hip Arthroplasty Using Cemented Collarless Double-Taper Femoral Components at a Mean Follow-Up of 13 Years (8 to 20): An Update
,”
Bone Joint J.
,
97B
(
8
), pp.
1038
1045
.
14.
Pijls
,
B. G.
,
Nieuwenhuijse
,
M. J.
,
Fiocco
,
M.
,
Plevier
,
J. W.
,
Middeldorp
,
S.
,
Nelissen
,
R. G.
, and
Valstar
,
E. R.
,
2012
, “
Early Proximal Migration of Cups is Associated With Late Revision in THA: A Systematic Review and Meta-Analysis of 26 RSA Studies and 49 Survival Studies
,”
Acta Orthop.
,
83
(
6
), pp.
583
591
.
15.
Klerken
,
T.
,
Mohaddes
,
M.
,
Nemes
,
S.
, and
Kärrholm
,
J.
,
2015
, “
High Early Migration of the Revised Acetabular Component is a Predictor of Late Cup Loosening: 312 Cup Revisions Followed With Radiostereometric Analysis for 2–20 Years
,”
Hip Int.
,
25
(
5
), pp.
471
476
.
16.
Søballe
,
K.
,
1993
, “
Hydroxyapatite Ceramic Coating for Bone Implant Fixation
,”
Acta Orthop. Scand.
,
64
(
Suppl. 255
), pp.
1
58
.
17.
Daugaard
,
H.
,
Elmengaard
,
B.
,
Andreassen
,
T.
,
Bechtold
,
J.
,
Lamberg
,
A.
, and
Soballe
,
K.
,
2011
, “
Parathyroid Hormone Treatment Increases Fixation of Orthopedic Implants With Gap Healing: A Biomechanical and Histomorphometric Canine Study of Porous Coated Titanium Alloy Implants in Cancellous Bone
,”
Calcif. Tissue Int.
,
88
(
4
), pp.
294
303
.
18.
Daugaard
,
H.
,
Elmengaard
,
B.
,
Andreassen
,
T. T.
,
Lamberg
,
A.
,
Bechtold
,
J. E.
, and
Soballe
,
K.
,
2012
, “
Systemic Intermittent Parathyroid Hormone Treatment Improves Osseointegration of Press-Fit Inserted Implants in Cancellous Bone
,”
Acta Orthop.
,
83
(
4
), pp.
411
419
.
19.
Søballe
,
K.
,
Chen
,
X.
,
Jensen
,
T. B.
,
Kidder
,
L.
, and
Bechtold
,
J. E.
,
2007
, “
Alendronate Treatment in the Revision Setting, With and Without Controlled Implant Motion: An Experimental Study in Dogs
,”
Acta Orthop.
,
78
(
6
), pp.
800
807
.
20.
Jensen
,
T. B.
,
Bechtold
,
J. E.
,
Chen
,
X.
, and
Søballe
,
K.
,
2007
, “
Systemic Alendronate Treatment Improves Fixation of Press-Fit Implants: A Canine Study Using Nonloaded Implants
,”
J. Orthop. Res.
,
25
(
6
), pp.
772
778
.
21.
Collins
,
F. S.
, and
Tabak
,
L. A.
,
2014
, “
Policy: NIH Plans to Enhance Reproducibility
,”
Nature
,
505
(
7485
), pp.
612
613
.
22.
Manolagas
,
S. C.
, and
Kronenberg
,
H. M.
,
2014
, “
Reproducibility of Results in Preclinical Studies: A Perspective From the Bone Field
,”
J. Bone Miner. Res.
,
29
(
10
), pp.
2131
2140
.
23.
Daugaard
,
H.
,
Elmengaard
,
B.
,
Bechtold
,
J. E.
,
Jensen
,
T.
, and
Soballe
,
K.
,
2010
, “
The Effect on Bone Growth Enhancement of Implant Coatings With Hydroxyapatite and Collagen Deposited Electrochemically and by Plasma Spray
,”
J. Biomed. Mater. Res. A.
,
92
(
3
), pp.
913
921
.
24.
Søballe
,
K.
,
Jensen
,
T. B.
,
Mouzin
,
O.
,
Kidder
,
L.
, and
Bechtold
,
J. E.
,
2004
, “
Differential Effect of a Bone Morphogenetic Protein-7 (OP-1) on Primary and Revision Loaded, Stable Implants With Allograft
,”
J. Biomed. Mater. Res. A.
,
71
(
4
), pp.
569
576
.
25.
Bechtold
,
J. E.
,
Mouzin
,
O.
,
Kidder
,
L.
, and
Søballe
,
K.
,
2001
, “
A Controlled Experimental Model of Revision Implants: Part II. Implementation With Loaded Titanium Implants and Bone Graft
,”
Acta Orthop. Scand.
,
72
(
6
), pp.
650
656
.
26.
Daugaard
,
H.
,
2011
, “
The Influence of Parathyroid Hormone Treatment on Implant Fixation
,”
Dan. Med. Bull.
,
58
(
9
), p.
B4317
.
27.
Daugaard
,
H.
,
Elmengaard
,
B.
,
Andreassen
,
T. T.
,
Baas
,
J.
,
Bechtold
,
J. E.
, and
Soballe
,
K.
,
2011
, “
The Combined Effect of Parathyroid Hormone and Bone Graft on Implant Fixation
,”
J. Bone Joint Surg. Br.
,
93
(
1
), pp.
131
139
.
28.
Elmengaard
,
B.
,
Bechtold
,
J. E.
,
Baas
,
J.
,
Jakobsen
,
T.
, and
Søballe
,
K.
,
2007
, “
Fixation of Revision Implants is Improved by the Surgical Technique of Cracking the Sclerotic Bone Rim Compared to Reaming
,”
53rd Annual Meeting of the Orthopaedic Research Society
, San Diego, CA, Feb. 11–14, p.
1727
.
29.
Pearce
,
A. I.
,
Richards
,
R. G.
,
Milz
,
S.
,
Schneider
,
E.
, and
Pearce
,
S. G.
,
2007
, “
Animal Models for Implant Biomaterial Research in Bone: A Review
,”
Eur. Cell Mater.
,
13
, pp.
1
10
.
30.
Virdi
,
A. S.
,
Irish
,
J.
,
Sena
,
K.
,
Liu
,
M.
,
Ke
,
H. Z.
,
McNulty
,
M. A.
, and
Sumner
,
D. R.
,
2015
, “
Sclerostin Antibody Treatment Improves Implant Fixation in a Model of Severe Osteoporosis
,”
J. Bone Joint Surg. Am.
,
97
(
2
), pp.
133
140
.
31.
Luangphakdy
,
V.
,
Walker
,
E.
,
Shinohara
,
K.
,
Pan
,
H.
,
Hefferan
,
T.
,
Bauer
,
T. W.
,
Stockdale
,
L.
,
Saini
,
S.
,
Dadsetan
,
M.
,
Runge
,
M. B.
,
Vasanji
,
A.
,
Griffith
,
L.
,
Yaszemski
,
M.
, and
Muschler
,
G. F.
,
2013
, “
Evaluation of Osteoconductive Scaffolds in the Canine Femoral Multi-Defect Model
,”
Tissue Eng., Part A.
,
19
(
5–6
), pp.
634
648
.
32.
Tsutsumi
,
R.
,
Hock
,
C.
,
Bechtold
,
C. D.
,
Proulx
,
S. T.
,
Bukata
,
S. V.
,
Ito
,
H.
,
Awad
,
H. A.
,
Nakamura
,
T.
,
O'Keefe
,
R. J.
, and
Schwarz
,
E. M.
,
2008
, “
Differential Effects of Biologic Versus Bisphosphonate Inhibition of Wear Debris-Induced Osteolysis Assessed by Longitudinal Micro-CT
,”
J. Orthop. Res.
,
26
(
10
), pp.
1340
1346
.
33.
Doube
,
M.
,
Kłosowski
,
M. M.
,
Arganda-Carreras
,
I.
,
Cordelières
,
F. P.
,
Dougherty
,
R. P.
,
Jackson
,
J. S.
,
Schmid
,
B.
,
Hutchinson
,
J. R.
, and
Shefelbine
,
S. J.
,
2010
, “
BoneJ: Free and Extensible Bone Image Analysis in ImageJ
,”
Bone
,
47
(
6
), pp.
1076
1079
.
34.
Kabel
,
J.
,
Odgaard
,
A.
,
van Rietbergen
,
B.
, and
Huiskes
,
R.
,
1999
, “
Connectivity and the Elastic Properties of Cancellous Bone
,”
Bone
,
24
(
2
), pp.
115
120
.
35.
Swider
,
P.
,
Pedrono
,
A.
,
Mouzin
,
O.
,
Søballe
,
K.
, and
Bechtold
,
J. E.
,
2006
, “
Biomechanical Analysis of the Shear Behaviour Adjacent to an Axially Loaded Implant
,”
J. Biomech.
,
39
(
10
), pp.
1873
1882
.
36.
Guérin
,
G.
,
Ambard
,
D.
, and
Swider
,
P.
,
2009
, “
Cells, Growth Factors and Bioactive Surface Properties in a Mechanobiological Model of Implant Healing
,”
J. Biomech.
,
42
(
15
), pp.
2555
2561
.
37.
Khalil
,
G.
,
Lorthois
,
S.
,
Marcoux
,
M.
,
Mansat
,
P.
, and
Swider
,
P.
,
2011
, “
Wave Front Migration of Endothelial Cells in a Bone–Implant Interface
,”
J. Biomech.
,
44
(
10
), pp.
1980
1986
.
38.
Khalil
,
G.
,
Mansat
,
P.
,
Søballe
,
K.
,
Bechtold
,
J. E.
, and
Swider
,
P.
,
2012
, “
A Reactive Model to Predict the Periprosthetic Healing
,”
Comput. Methods Biomech. Biomed. Eng.
,
15
(
Suppl. 1
), pp.
21
22
.
39.
Swider
,
P.
,
Ambard
,
D.
,
Guérin
,
G.
,
Søballe
,
K.
, and
Bechtold
,
J. E.
,
2011
, “
Sensitivity Analysis of Periprosthetic Healing to Cell Migration, Growth Factor and Post-Operative Gap Using a Mechanobiological Model
,”
Comput. Methods Biomech. Biomed. Eng.
,
14
(
9
), pp.
763
771
.
40.
Bailón-Plaza
,
A.
, and
van der Meulen
,
M. C.
,
2001
, “
A Mathematical Framework to Study the Effects of Growth Factor Influences on Fracture Healing
,”
J. Theor. Biol.
,
212
(
2
), pp.
191
209
.
41.
Anderson
,
A. R.
, and
Chaplain
,
M. A.
,
1998
, “
Continuous and Discrete Mathematical Models of Tumor-Induced Angiogenesis
,”
Bull. Math. Biol.
,
60
(
5
), pp.
857
899
.
42.
Yang
,
J.
,
Faverjon
,
B.
,
Dureisseix
,
D.
,
Swider
,
P.
, and
Kessissoglou
,
N.
,
2014
, “
Stochastic Porous Model of a Bone–Implant Healing Process Using Polynomial Chaos Expansion
,”
43rd International Congress on Noise Control Engineering
(
inter.noise 2014
), Melbourne, Australia, Nov. 16–19, p.
801
.
43.
Comadoll
,
J. L.
,
Bianco
,
P. T.
,
Bechtold
,
J. E.
, and
Gustilo
,
R. B.
,
1991
, “
Association Between Mechanical Stability, Cortical Strains and Histology of Femurs Retrieved With Uncemented Femoral Prostheses
,”
15th Annual Meeting of the American Society of Biomechanics
, Tempe, AZ, Oct. 16–18, p.
136
.
44.
Mouzin
,
O.
,
Søballe
,
K.
, and
Bechtold
,
J. E.
,
2001
, “
Loading Improves Anchorage of Hydroxyapatite Implants More Than Titanium Implants
,”
J. Biomed. Mater. Res.
,
58
(
1
), pp.
61
68
.
45.
Nieuwenhuijse
,
M. J.
,
Valstar
,
E. R.
,
Kaptein
,
B. L.
, and
Nelissen
,
R. G.
,
2012
, “
Good Diagnostic Performance of Early Migration as a Predictor of Late Aseptic Loosening of Acetabular Cups: Results From Ten Years of Follow-Up With Roentgen Stereophotogrammetric Analysis (RSA)
,”
J. Bone Joint Surg. Am.
,
94
(
10
), pp.
874
880
.
You do not currently have access to this content.