Host bone microstructure for enhanced resistance to bacterial infections

[1] C. Cathleen, C. Bernard, Knee arthroplasty surgical site infection rates over a tenyear period at a community hospital, Am. J. Infect. Control 41 (2013) S112–S113,

https://doi.org/10.1016/j.ajic.2013.03.228.

[2] S.P. Nota, Y. Braun, D. Ring, J.H. Schwab, Incidence of surgical site infection after

spine surgery: what is the impact of the definition of infection? Clin. Orthop. Relat.

Res. 473 (2015) 1612–1619, https://doi.org/10.1007/s11999-014-3933-y.

[3] B. Zmistowski, J.A. Karam, J.B. Durinka, D.S. Casper, J. Parvizi, Periprosthetic

joint infection increases the risk of one-year mortality, J. Bone Joint Surg. Am. 95

(2013) 2177–2184, https://doi.org/10.2106/JBJS.L.00789.

[4] S.M. Kurtz, E. Lau, H. Watson, J.K. Schmier, J. Parvizi, Economic burden of

periprosthetic joint infection in the United States, J. Arthroplast. 27 (Supplement)

(2012), https://doi.org/10.1016/j.arth.2012.02.022 (61–5.e1).

[5] D.S. Casper, B. Zmistowski, D.A. Hollern, A.S. Hilibrand, A.R. Vaccaro, G.

D. Schroeder, C.K. Kepler, The effect of postoperative spinal infections on patient

mortality, Spine 43 (2018) 223–227, https://doi.org/10.1097/

BRS.0000000000002277.

[6] A.M. Schwartz, K.X. Farley, G.N. Guild, T.L. Bradbury Jr., Projections and

epidemiology of revision hip and knee arthroplasty in the United States to 2030,

J. Arthroplasty 35 (2020) S79–S85, https://doi.org/10.1016/j.arth.2020.02.030.

[7] S.S. Rajaee, H.W. Bae, L.E. Kanim, R.B. Delamarter, Spinal fusion in the United

States: analysis of trends from 1998 to 2008, Spine 37 (2012) 67–76, https://doi.

org/10.1097/BRS.0b013e31820cccfb.

[8] J.S. Smith, C.I. Shaffrey, C.A. Sansur, S.H. Berven, K.M. Fu, P.A. Broadstone, T.

J. Choma, M.J. Goytan, H.H. Noordeen, D.R. Knapp Jr., R.A. Hart, W.

F. Donaldson 3rd, D.W. Polly Jr., J.H. Perra, O. Boachie-Adjei, Scoliosis Research

Society Morbidity and Mortality Committee, Rates of infection after spine surgery

based on 108,419 procedures: a report from the Scoliosis Research Society

Morbidity and Mortality Committee, Spine 36 (2011) 556–563, https://doi.org/

10.1097/BRS.0b013e3181eadd41.

[9] J. Chahoud, Z. Kanafani, S.S. Kanj, Surgical site infections following spine surgery:

eliminating the controversies in the diagnosis, Front. Med. (Lausanne) 1 (2014) 7,

https://doi.org/10.3389/fmed.2014.00007.

[10] H. Segawa, D.T. Tsukayama, R.F. Kyle, D.A. Becker, R.B. Gustilo, Infection after

total knee arthroplasty. A retrospective study of the treatment of eighty-one

infections, J. Bone Joint Surg. Am. 81 (1999) 1434–1445, https://doi.org/

10.2106/00004623-199910000-00008.

[11] K. Huotari, M. Peltola, E. J¨

amsen, The incidence of late prosthetic joint infections:

a registry-based study of 112,708 primary hip and knee replacements, Acta Orthop.

86 (2015) 321–325, https://doi.org/10.3109/17453674.2015.1035173.

[12] K. Maruo, S.H. Berven, Outcome and treatment of postoperative spine surgical site

infections: predictors of treatment success and failure, J. Orthop. Sci. 19 (2014)

398–404, https://doi.org/10.1007/s00776-014-0545-z.

[13] B.R. Richards, K.M. Emara, Delayed infections after posterior TSRH spinal

instrumentation for idiopathic scoliosis: revisited, Spine 26 (2001) 1990–1996,

https://doi.org/10.1097/00007632-200109150-00009.

[14] T.J. Kowalski, E.F. Berbari, P.M. Huddleston, J.M. Steckelberg, J.N. Mandrekar, D.

R. Osmon, The management and outcome of spinal implant infections:

contemporary retrospective cohort study, Clin. Infect. Dis. 44 (2007) 913–920,

https://doi.org/10.1086/512194.

[15] T. Morimoto, H. Hirata, S. Eto, A. Hashimoto, S. Kii, T. Kobayashi, M. Tsukamoto,

T. Yoshihara, Y. Toda, M. Mawatari, Development of silver-containing

hydroxyapatite-coated antimicrobial implants for orthopaedic and spinal surgery,

Medicina (Kaunas) 58 (2022) 519, https://doi.org/10.3390/medicina58040519.

[16] O.D. Savvidou, A. Kaspiris, I. Trikoupis, G. Kakouratos, S. Goumenos,

D. Melissaridou, P.J. Papagelopoulos, Efficacy of antimicrobial coated orthopaedic

implants on the prevention of periprosthetic infections: a systematic review and

meta-analysis, J. Bone Jt. Infect. 5 (2020) 212–222, https://doi.org/10.7150/

jbji.44839.

[17] M. Fiore, A. Sambri, R. Zucchini, C. Giannini, D.M. Donati, M. De Paolis, Silvercoated megaprosthesis in prevention and treatment of peri-prosthetic infections: a

systematic review and meta-analysis about efficacy and toxicity in primary and

revision surgery, Eur. J. Orthop. Surg. Traumatol. 31 (2021) 201–220, https://doi.

org/10.1007/s00590-020-02779-z.

[18] I. Noda, F. Miyaji, Y. Ando, H. Miyamoto, T. Shimazaki, Y. Yonekura, M. Miyazaki,

M. Mawatari, T. Hotokebuchi, Development of novel thermal sprayed antibacterial

coating and evaluation of release properties of silver ions, J. Biomed. Mater. Res. B

Appl. Biomater. 89 (2009) 456–465, https://doi.org/10.1002/jbm.b.31235.

[19] B. Wang, A. Bian, F. Jia, J. Lan, H. Yang, K. Yan, L. Xie, H. Qiao, X. Chang, H. Lin,

H. Zhang, Y. Huang, “Dual-functional” strontium titanate nanotubes designed

based on fusion peptides simultaneously enhancing anti-infection and

osseointegration, Biomater. Adv. 133 (2022), 112650, https://doi.org/10.1016/j.

msec.2022.112650.

[20] B. Wang, Z. Wu, S. Wang, S. Wang, Q. Niu, Y. Wu, F. Jia, A. Bian, L. Xie, H. Qiao,

X. Chang, H. Lin, H. Zhang, Y. Huang, Mg/cu-doped TiO2 nanotube array: a novel

dual-function system with self-antibacterial activity and excellent cell

compatibility, Mater. Sci. Eng. C 128 (2021), 112322, https://doi.org/10.1016/j.

msec.2021.112322.

[21] B. Wang, Z. Wu, J. Lan, Y. Li, L. Xie, X. Huang, A. Zhang, H. Qiao, X. Chang, H. Lin,

H. Zhang, T. Li, Y. Huang, Surface modification of titanium implants by silk

fibroin/Ag co-functionalized strontium titanate nanotubes for inhibition of

[23]

[24]

[25]

[26]

[27]

[28]

[29]

[30]

[31]

[32]

[33]

[34]

[35]

[36]

[37]

[38]

[39]

[40]

[41]

bacterial-associated infection and enhancement of in vivo osseointegration, Surf.

Coat. Technol. 405 (2021), 126700, https://doi.org/10.1016/j.

surfcoat.2020.126700.

Y. Huang, Y. Zhang, M. Li, H. Yang, J. Liang, Y. Chen, Y. Zhang, X. Huang, L. Xie,

H. Lin, H. Qiao, J. Lan, Physicochemical, osteogenic and antimicrobial properties

of graphene oxide reinforced silver/strontium-doped hydroxyapatite on titanium

for potential orthopedic applications, Surf. Coat. Technol. 446 (2022), 128788,

https://doi.org/10.1016/j.surfcoat.2022.128788.

B. Wang, Y. Li, S. Wang, F. Jia, A. Bian, K. Wang, L. Xie, K. Yan, H. Qiao, H. Lin,

J. Lan, Y. Huang, Electrodeposited dopamine/strontium-doped hydroxyapatite

composite coating on pure zinc for anti-corrosion, antimicrobial and osteogenesis,

Mater. Sci. Eng. C 129 (2021), 112387, https://doi.org/10.1016/j.

msec.2021.112387.

A.G. Gristina, Biomaterial-centered infection: microbial adhesion versus tissue

integration, Science 237 (1987) 1588–1595, https://doi.org/10.1126/

science.3629258.

H.J. Busscher, H.C. van der Mei, G. Subbiahdoss, P.C. Jutte, J.J. van den Dungen, S.

A. Zaat, M.J. Schultz, D.W. Grainger, Biomaterial-associated infection: locating the

finish line in the race for the surface, Sci. Transl. Med. 4 (2012), 153rv10, https://

doi.org/10.1126/scitranslmed.3004528.

S. Zhang, L. Wang, L. Bao, H. Sun, F. Feng, J. Shan, H. Tang, Does rheumatoid

arthritis affect the infection and complications rates of spinal surgery? A systematic

review and meta-analysis, World Neurosurg. 145 (2021) 260–266, https://doi.org/

10.1016/j.wneu.2020.09.039.

B. Ravi, B. Escott, P.S. Shah, R. Jenkinson, J. Chahal, E. Bogoch, H. Kreder,

G. Hawker, A systematic review and meta-analysis comparing complications

following total joint arthroplasty for rheumatoid arthritis versus for osteoarthritis,

Arthritis Rheum. 64 (2012) 3839–3849, https://doi.org/10.1002/art.37690.

R. Ozasa, A. Matsugaki, T. Ishimoto, S. Kamura, H. Yoshida, M. Magi,

Y. Matsumoto, K. Sakuraba, K. Fujimura, H. Miyahara, T. Nakano, Bone fragility

via degradation of bone quality featured by collagen/apatite micro-arrangement in

human rheumatic arthritis, Bone 155 (2022), 116261, https://doi.org/10.1016/j.

bone.2021.116261.

T. Ishimoto, T. Nakano, Y. Umakoshi, M. Yamamoto, Y. Tabata, Degree of

biological apatite c-axis orientation rather than bone mineral density controls

mechanical function in bone regenerated using recombinant bone morphogenetic

protein-2, J. Bone Miner. Res. 28 (2013) 1170–1179, https://doi.org/10.1002/

jbmr.1825.

A. Matsugaki, S. Matsumoto, T. Nakano, A novel role of interleukin-6 as a

regulatory factor of inflammation-associated deterioration in osteoblast

arrangement, Int. J. Mol. Sci. 21 (2020) 1–11, https://doi.org/10.3390/

ijms21186659.

A. Matsugaki, Y. Isobe, T. Saku, T. Nakano, Quantitative regulation of bonemimetic, oriented collagen/apatite matrix structure depends on the degree of

osteoblast alignment on oriented collagen substrates, J. Biomed. Mater. Res. A 103

(2015) 489–499, https://doi.org/10.1002/jbm.a.35189.

S. Zaatreh, K. Wegner, M. Strauß, J. Pasold, W. Mittelmeier, A. Podbielski,

B. Kreikemeyer, R. Bader, Co-culture of S. epidermidis and human osteoblasts on

implant surfaces: an advanced in vitro model for implant-associated infections,

PLOS ONE 11 (2016), e0151534, https://doi.org/10.1371/journal.pone.0151534.

Y. Yang, H. Ao, Y. Wang, W. Lin, S. Yang, S. Zhang, Z. Yu, T. Tang,

Cytocompatibility with osteogenic cells and enhanced in vivo anti-infection

potential of quaternized chitosan-loaded titania nanotubes, Bone Res. 4 (2016)

16027, https://doi.org/10.1038/boneres.2016.27.

Y. Kanda, Investigation of the freely available easy-to-use software “EZR” for

medical statistics, Bone Marrow Transplant. 48 (2013) 452–458, https://doi.org/

10.1038/bmt.2012.244.

T. Ishimoto, K. Yamada, H. Takahashi, M. Takahata, M. Ito, T. Hanawa, T. Nakano,

Trabecular health of vertebrae based on anisotropy in trabecular architecture and

collagen/apatite micro-arrangement after implantation of intervertebral fusion

cages in the sheep spine, Bone. 108 (2018) 25–33, https://doi.org/10.1016/j.

bone.2017.12.012.

A. Sekita, A. Matsugaki, T. Nakano, Disruption of collagen/apatite alignment

impairs bone mechanical function in osteoblastic metastasis induced by prostate

cancer, Bone 97 (2017) 83–93, https://doi.org/10.1016/j.bone.2017.01.004.

R. Ozasa, T. Ishimoto, S. Miyabe, J. Hashimoto, M. Hirao, H. Yoshikawa,

T. Nakano, Osteoporosis changes collagen/apatite orientation and Young’s

modulus in vertebral cortical bone of rat, Calcif. Tissue Int. 104 (2019) 449–460,

https://doi.org/10.1007/s00223-018-0508-z.

G. Slyamova, A. Gusmanov, A. Batpenov, N. Kaliev, D. Viderman, Risk factors for

postoperative osteomyelitis among patients after bone fracture: a matched casecontrol study, J. Clin. Med. 11 (2022) 6072, https://doi.org/10.3390/

jcm11206072.

D. Franco, M. Klingauf, M. Bednarzik, M. Cecchini, V. Kurtcuoglu, J. Gobrecht,

D. Poulikakos, A. Ferrari, Control of initial endothelial spreading by topographic

activation of focal adhesion kinase, Soft Matter 7 (2011) 7313–7324, https://doi.

org/10.1039/c1sm05191a.

M. Schernthaner, G. Leitinger, H. Wolinski, S.D. Kohlwein, B. Reisinger, R.A. Barb,

W.F. Graier, J. Heitz, K. Groschner, Enhanced Ca2+ entry and tyrosine

phosphorylation mediate nanostructure-induced endothelial proliferation,

J. Nanomater. 2013 (2013), 251063, https://doi.org/10.1155/2013/251063.

S. Lee, A. Matsugaki, T. Kasuga, T. Nakano, Development of bifunctional oriented

bioactive glass/poly(lactic acid) composite scaffolds to control osteoblast

alignment and proliferation, J. Biomed. Mater. Res. A 107 (2019) 1031–1041,

https://doi.org/10.1002/jbm.a.36619.

R. Watanabe et al.

Biomaterials Advances 154 (2023) 213633

[42] T. Ishimoto, Y. Kobayashi, M. Takahata, M. Ito, A. Matsugaki, H. Takahashi,

R. Watanabe, T. Inoue, T. Matsuzaka, R. Ozasa, T. Hanawa, K. Yokota,

Y. Nakashima, T. Nakano, Outstanding in vivo mechanical integrity of additively

manufactured spinal cages with a novel “honeycomb tree structure” design via

guiding bone matrix orientation, Spine J. 22 (2022) 1742–1757, https://doi.org/

10.1016/j.spinee.2022.05.006.

[43] L. Chu, Y. Yang, S. Yang, Q. Fan, Z. Yu, X.L. Hu, T.D. James, X.P. He, T. Tang,

Preferential colonization of osteoblasts over co-cultured bacteria on a bifunctional

biomaterial surface, Front. Microbiol. 9 (2018) 2219, https://doi.org/10.3389/

fmicb.2018.02219.

[44] L. Cr´emet, A. Broquet, B. Brulin, C. Jacqueline, S. Dauvergne, R. Brion,

K. Asehnoune, S. Corvec, D. Heymann, N. Caroff, Pathogenic potential of

Escherichia coli clinical strains from orthopedic implant infections towards human

osteoblastic cells, Pathog. Dis. 73 (2015), ftv065, https://doi.org/10.1093/

femspd/ftv065.

[45] X. Pierrat, J.P.H. Wong, Z. Al-Mayyah, A. Persat, The Mammalian membrane

microenvironment regulates the sequential attachment of bacteria to host cells,

mBio 12 (2021), e0139221, https://doi.org/10.1128/mBio.01392-21.

[46] G.C. Reilly, T.R. Haut, C.E. Yellowley, H.J. Donahue, C.R. Jacobs, Fluid flow

induced PGE2 release by bone cells is reduced by glycocalyx degradation whereas

calcium signals are not, Biorheology 40 (2003) 591–603.

[47] Y. Yao, A. Rabodzey, C.F. Dewey Jr., Glycocalyx modulates the motility and

proliferative response of vascular endothelium to fluid shear stress, Am. J. Physiol.

Heart Circ. Physiol. 293 (2007) H1023–H1030, https://doi.org/10.1152/

ajpheart.00162.2007.

[48] Y. Zeng, J.M. Tarbell, The adaptive remodeling of endothelial glycocalyx in

response to fluid shear stress, PloS One 9 (2014), e86249, https://doi.org/

10.1371/journal.pone.0086249.

[49] W. Li, W. Wang, Structural alteration of the endothelial glycocalyx: contribution of

the actin cytoskeleton, Biomech. Model. Mechanobiol. 17 (2018) 147–158, https://

doi.org/10.1007/s10237-017-0950-2.

[50] G. Subbiahdoss, R. Kuijer, D.W. Grijpma, H.C. van der Mei, H.J. Busscher,

Microbial biofilm growth vs. tissue integration: “the race for the surface”

experimentally studied, Acta Biomater. 5 (2009) 1399–1404, https://doi.org/

10.1016/j.actbio.2008.12.011.

[51] U. Dapunt, T. Giese, S. Stegmaier, A. Moghaddam, G.M. H¨

ansch, The osteoblast as

an inflammatory cell: production of cytokines in response to bacteria and

components of bacterial biofilms, BMC Musculoskelet. Disord. 17 (2016) 243,

https://doi.org/10.1186/s12891-016-1091-y.

[52] I. Marriott, D.L. Gray, S.L. Tranguch, V.G. Fowler Jr., M. Stryjewski, L. Scott Levin,

M.C. Hudson, K.L. Bost, Osteoblasts express the inflammatory cytokine interleukin6 in a murine model of Staphylococcus aureus osteomyelitis and infected human

bone tissue, Am. J. Pathol. 164 (2004) 1399–1406, https://doi.org/10.1016/

S0002-9440(10)63226-9.

[53] H. Wang, L. Qin, J. Wang, W. Huang, Synovial fluid IL-1β appears useful for the

diagnosis of chronic periprosthetic joint infection, J. Orthop. Surg. Res. 16 (2021)

144, https://doi.org/10.1186/s13018-021-02296-7.

[54] L. Qin, C. Du, J. Yang, H. Wang, X. Su, L. Wei, C. Zhao, C. Chen, H. Chen, N. Hu,

W. Huang, Synovial fluid interleukin levels cannot distinguish between prosthetic

joint infection and active rheumatoid arthritis after hip or knee arthroplasty,

Diagnostics (Basel) 12 (2022) 1196, https://doi.org/10.3390/

diagnostics12051196.

[55] J.J. Cush, J.B. Splawski, R. Thomas, J.E. McFarlin, H. Schulze-Koops, L.S. Davis,

K. Fujita, P.E. Lipsky, Elevated interleukin-10 levels in patients with rheumatoid

arthritis, Arthritis Rheum. 38 (1995) 96–104, https://doi.org/10.1002/

art.1780380115.

[56] C. Fiehn, M. Wermann, A. Pezzutto, M. Hüfner, B. Heilig, Plasma GM-CSF

concentrations in rheumatoid arthritis, systemic lupus erythematosus and

spondyloarthropathy, Z. Rheumatol. 51 (1992) 121–126.

[57] F.S. Fr¨

oschen, S. Schell, F.A. Schildberg, A. Klausing, H. Kohlhof, S. Gravius, T.

M. Randau, Analysis of synovial biomarkers with a multiplex protein microarray in

patients with PJI undergoing revision arthroplasty of the hip or knee joint, Arch.

Orthop. Trauma Surg. 140 (2020) 1883–1890, https://doi.org/10.1007/s00402020-03388-5.

[58] R.V. Lokhande, J.G. Ambekar, K.G. Bhat, N.N. Dongre, Interleukin-21 and its

association with chronic periodontitis, J. Indian Soc. Periodontol. 23 (2019)

21–24, https://doi.org/10.4103/jisp.jisp_410_18.

[59] A. Jüngel, J.H. Distler, M. Kurowska-Stolarska, C.A. Seemayer, R. Seibl, A. Forster,

B.A. Michel, R.E. Gay, F. Emmrich, S. Gay, O. Distler, Expression of interleukin-21

[60]

[61]

[62]

[63]

[64]

[65]

[66]

[67]

[68]

[69]

[70]

[71]

[72]

[73]

[74]

[75]

receptor, but not interleukin-21, in synovial fibroblasts and synovial macrophages

of patients with rheumatoid arthritis, Arthritis Rheum. 50 (2004) 1468–1476,

https://doi.org/10.1002/art.20218.

Y. Okamatsu, D. Kim, R. Battaglino, H. Sasaki, U. Sp¨

ate, P. Stashenko, MIP-1

gamma promotes receptor-activator-of-NF-kappa-B-ligand-induced osteoclast

formation and survival, J. Immunol. 173 (2004) 2084–2090, https://doi.org/

10.4049/jimmunol.173.3.2084.

M. Yang, G. Mailhot, C.A. MacKay, A. Mason-Savas, J. Aubin, P.R. Odgren,

Chemokine and chemokine receptor expression during colony stimulating factor-1induced osteoclast differentiation in the toothless osteopetrotic rat: a key role for

CCL9 (MIP-1 gamma) in osteoclastogenesis in vivo and in vitro, Blood 107 (2006)

2262–2270, https://doi.org/10.1182/blood-2005-08-3365.

D. Varoga, M. Tohidnezhad, F. Paulsen, C.J. Wruck, L. Brandenburg, R. Mentlein,

S. Lippross, J. Hassenpflug, L. Besch, M. Müller, C. Jürgens, A. Seekamp,

L. Schmitt, T. Pufe, The role of human beta-defensin-2 in bone, J. Anat. 213 (2008)

749–757, https://doi.org/10.1111/j.1469-7580.2008.00992.x.

D. Varoga, C.J. Wruck, M. Tohidnezhad, L. Brandenburg, F. Paulsen, R. Mentlein,

A. Seekamp, L. Besch, T. Pufe, Osteoblasts participate in the innate immunity of the

bone by producing human beta defensin-3, Histochem. Cell Biol. 131 (2009)

207–218, https://doi.org/10.1007/s00418-008-0522-8.

F. Semple, J.R. Dorin, β-defensins: multifunctional modulators of infection,

inflammation and more? J. Innate Immun. 4 (2012) 337–348, https://doi.org/

10.1159/000336619.

F. Semple, S. Webb, H.N. Li, H.B. Patel, M. Perretti, I.J. Jackson, M. Gray, D.

J. Davidson, J.R. Dorin, Human beta-defensin 3 has immunosuppressive activity in

vitro and in vivo, Eur. J. Immunol. 40 (2010) 1073–1078, https://doi.org/

10.1002/eji.200940041.

K.R. Parducho, B. Beadell, T.K. Ybarra, M. Bush, E. Escalera, A.T. Trejos, A. Chieng,

M. Mendez, C. Anderson, H. Park, Y. Wang, W. Lu, E. Porter, The antimicrobial

peptide human beta-defensin 2 inhibits biofilm production of Pseudomonas

aeruginosa without compromising metabolic activity, Front. Immunol. 11 (2020)

805, https://doi.org/10.3389/fimmu.2020.00805.

A.G. Hanan, A.S. Ahmed, Effect of β-defensin 2 on biofilm formation in pathogenic

E. coli bacteria isolated from clinical samples, TJABS 4 (2022) 76–80.

J. Harder, J. Bartels, E. Christophers, J.M. Schroder, Isolation and characterization

of human beta -defensin-3, a novel human inducible peptide antibiotic, J. Biol.

Chem. 276 (2001) 5707–5713, https://doi.org/10.1074/jbc.M008557200.

D.M. Hoover, Z. Wu, K. Tucker, W. Lu, J. Lubkowski, Antimicrobial

characterization of human β-defensin 3 derivatives, Antimicrob. Agents

Chemother. 47 (2003) 2804–2809, https://doi.org/10.1128/AAC.47.9.28042809.2003.

A. Matsugaki, M. Ito, Y. Kobayashi, T. Matsuzaka, R. Ozasa, T. Ishimoto,

H. Takahashi, R. Watanabe, T. Inoue, K. Yokota, Y. Nakashima, T. Kaito, S. Okada,

T. Hanawa, Y. Matsuyama, M. Matsumoto, H. Taneichi, T. Nakano, Innovative

design of bone quality-targeted intervertebral spacer: accelerated functional fusion

guiding oriented collagen and apatite microstructure without autologous bone

graft, Spine J. 23 (2023) 609–620, https://doi.org/10.1016/j.spinee.2022.12.011.

T. Ishimoto, K. Kawahara, A. Matsugaki, H. Kamioka, T. Nakano, Quantitative

evaluation of osteocyte morphology and bone anisotropic extracellular matrix in

rat femur, Calcif. Tissue Int. 109 (2021) 434–444, https://doi.org/10.1007/

s00223-021-00852-1.

R. Watanabe, A. Matsugaki, T. Ishimoto, R. Ozasa, T. Matsumoto, T. Nakano,

A novel ex vivo bone culture model for regulation of collagen/apatite preferential

orientation by mechanical loading, Int. J. Mol. Sci. 23 (2022) 7423, https://doi.

org/10.3390/ijms23137423.

B. Mirzashahi, M. Chehrassan, S.M.J. Mortazavi, Intrawound application of

vancomycin changes the responsible germ in elective spine surgery without

significant effect on the rate of infection: a randomized prospective study,

Musculoskelet. Surg. 102 (2018) 35–39, https://doi.org/10.1007/s12306-0170490-z.

L. Pulido, E. Ghanem, A. Joshi, J.J. Purtill, J. Parvizi, Periprosthetic joint infection:

the incidence, timing, and predisposing factors, Clin. Orthop. Relat. Res. 466

(2008) 1710–1715, https://doi.org/10.1007/s11999-008-0209-4.

M.F. Chen, C.H. Chang, C.C. Hu, Y.Y. Wu, Y. Chang, S.W.N. Ueng, Periprosthetic

joint infection caused by gram-positive versus gram-negative bacteria:

lipopolysaccharide, but not lipoteichoic acid, exerts adverse osteoclast-mediated

effects on the bone, J. Clin. Med. 8 (2019) 1289, https://doi.org/10.3390/

jcm8091289.

...