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Silica coated high performance oxide ceramics promote greater ossification than titanium implants: an in vivo study



This in vitro study investigated the osseointegration and implant integration of high performance oxide ceramics (HPOC) compared to titanium implants in rabbits.


Histomorphometry was conducted around the distal, proximal, medial, and lateral aspects of the HPOC to quantify the amount of mature and immature ossification within the bone interface. Histomorphometry was conducted by a trained musculoskeletal pathologist. The region of interest (ROI) represented the percentage of surrounding area of the implant. The percentage of ROI covered by osteoid implant contact (OIC) and mature bone implant contact (BIC) were assessed. The surrounding presence of bone resorption, necrosis, and/or inflammation were quantitatively investigated.


All 34 rabbits survived the 6- and 12-week experimental period. All HPOC implants remained in situ. The mean weight difference from baseline was + 647.7 mg (P < 0.0001). The overall OIC of the ceramic group was greater at 6 weeks compared to the titanium implants (P = 0.003). The other endpoints of interest were similar between the two implants at all follow-up points. No difference was found in BIC at 6- and 12-weeks follow-up. No bone necrosis, resorption, or inflammation were observed.


HPOC implants demonstrated a greater osteoid implant contact at 6 weeks compared to the titanium implants, with no difference found at 12 weeks. The percentage of bone implant contact of HPOC implants was similar to that promoted by titanium implants.


Alloy implants are commonly used in musculoskeletal medicine [1]. Bony osteointegration is pivotal to ensure implant survivorship. Osseointegration is a foreign body reaction to shield off the implant from the tissues [2]. Osteointegration is the capability of the implant to fuse with the surrounding bone, interacting and integrating with it [3, 4]. The rate of aseptic loosening and related consequences (stress-shielding, persistent pain, inflammation) are still a concern in musculoskeletal medicine following implantation of foreign materials [5, 6]. Given their optimal ossification, titanium and its alloys are commonly used [7,8,9]. High performance oxide ceramics (HPOC) has attracted much interest [10, 11]. HPOC have several advantages: high hardness and wear resistance, light weight, outstanding resistance to creep and compressive stress, and avoid imaging artefacts [12,13,14]. However, the biologically inactivity of ceramics, and consequently limited potential for integration, may limit their application. To overcome this limitation to clinical application, HPOC biologically functionalised with a silicate coating alumina AL2O3 have been developed [15, 16]. HPOC implants have been recently introduced in musculoskeletal medicine, and their application has been successfully supported by recently published clinical trials [17,18,19,20,21,22,23,24]. HPOC have been developed and investigated at our institution during the past years. The strength of the bonding between the functionalised ceramic and surrounding layer was evaluated by the application of polymethyl methacrylate (PMMA) to the surface, as per manufacturer instructions [25]. The contact guidance, adhesions, surrounding mesenchymal stromal cells osteogenic differentiation, and their cytotoxic potential has also been evaluated in previous studies conducted at our institution [25, 26]. An experimental study in rabbits was conducted to characterise osseointegration and implant integration of HPOC. The bone implant interface is responsible for the primary and secondary stability of the implant, and it is suggested to be the weakest domain in the bone implant system, where most failures occur [27, 28]. We hypothesised that HPOC implants promote ossification and transplant integration. To validate this hypothesis, osteointegration of HPOC were compared to that provided by commercial titanium implants. Histomorphometry was conducted around the distal, proximal, medial, and lateral aspect of the HPOC implants to quantify the amount of mature and immature ossification within the bone implant interface.

Materials and method

Type of implants

For the experimental group, HPOC were manufactured and functionalized at the RWTH University Aachen, Germany, Department of Dental Materials Science and Biomaterial Research in a previously published fashion [25, 26, 29, 30]. Briefly, standard 5.5 × 8 mm Al2O3 ceramic based cylinders were used. To facilitate the coupling of stable organosilane monolayers on the monolithic Al2O3 ceramic based cylinders, plasma-enhanced chemical vapor deposition (PE-CVD) was performed [31]. Silicon suboxide (SiOx) was deposited on the polished and cleaned Al2O3 ceramic based cylinders to activate the ceramics [32]. Functionalised ceramic cylinders were then air-dried, cured at 80° for 45 min, and stored in liquid nitrogen until use. For the control group, Sandblasted titanium Ti-6Al-4 V 5.5 × 8 mm implants (Zimmer Biomet GmbH, Neu-Ulm, Germany) were used.

Surgical procedure

The present investigation was conducted following the Animal Welfare Act of the Federal Republic of Germany in 2017, and approved by the Federal Office for Nature, Environment and Consumer Protection (Landesamt für Natur, Umwelt und Verbraucherschutz, LANU) of North Rhine-Westphalia, Federal Republic of Germany (Approval ID: 84–02.04.2016.A434). 34 New Zealand adult female white rabbits (weight > 3 kg) were used. Rabbits were allocated into four groups (Fig. 1).

Fig. 1
figure 1

Group allocation

0.1 ml/mg/kg bodyweight Medetomidin (Domitor) combined with a 0.2 ml Ketamin (Narketan) in a subcutaneous injection were used to induct the anaesthesia. The surgical site was shaved, disinfected with iodine and ethanol, and draped in a sterile fashion. 10 mg/kg bodyweight Enrofloxacin subcutaneous injection were injected before the incision. The skin incision was performed over the right lateral femoral condyle. After dissection through fascia and muscles, the condyle was exposed, and the lateral collateral ligament identified. With a 5.5 mm trephine, a unicortical drill hole was performed under irrigation to avoid thermal necrosis, making sure that the lateral collateral ligament was sparred. Once the bony cylinder was extracted, either a titanium or HPCO cylinder was inserted in a press fit fashion, without damaging the knee capsule. Tissues were closed in layers in a standard fashion. Finally, the skin was stapled and sprayed with chelated silver. For the first three days after surgery, 4 mg/kg bodyweight Carprofen were administered every 24 h. Six or 12 weeks postoperatively, the rabbits were euthanised using 2 ml/kg bodyweight Natriumpentobarbital (160 mg Natriumpentobarbital/ml). The femoral condyles were harvested and examined.

Sample preparation

The femoral condyles were harvested en bloc. Fixation was performed over 12 days with 4% paraformaldehyde followed by an alcohol series with ethanol of 50–100% and xylol. The specimens were embedded in Technovit® 9100 (Kulzer GmbH, Hanau, Germany). Using a diamond band saw Exakt 300CL (EXAKT Technologies Inc, Oklahoma City, US), 60–70 µm coplanar cuts of the specimens were performed. Grinding of titanium cylinders was conducted using sandpaper, while HPCO implants were ground with diamond paper. All specimens were stained with haematoxylin eosin, trichrome, and toluidine. Histomorphometry was conducted by a professional pathologist with OLYMPUS digital microscope DSX-1000 and stream desktop- Software (Olympus Hamburg, Germany).


At microscopy, specimens were divided as follows: lateral (K1), distal (K2), medial (K3), and proximal (K4). The surrounding area between the bone-implant interface (red zones) was the region of interest (ROI, Fig. 2).

Fig. 2
figure 2

Left: Microscopy evaluation strategy of the BIC: K2 and K4 (longer sides) accounted for 60% (30% each) and the K1 and K3 (shorter sides) for 40% (20% each). Right: Region of interest

The outcome of interest was to investigate the potential of osteointegration of HPCO in comparison to the standard titanium. Hence, the percentage immature, and unmineralized bone matrix (osteoid implant contact, OIC) within the ROI was assessed. The percentage of mature, mineralized bone (bone implant contact, BIC) within the ROI was also quantified. The surrounding presence of bone resorption, necrosis, and/or inflammation were quantitatively evaluated and classified as follows: 0 (none), 1 (minimal), 2 (low), 3 (moderate), 4 (severe).

Statistical analysis

The IBM SPSS (version 25) was used for statistical analyses. Mean and standard deviation were used for descriptive statistics. The mean difference effect measure was adopted for continuous variables, with standard error (SE) and 95% confidence interval (CI). Values of t-test < 0.05 were considered statistically significant.


Animal data

All 34 rabbits survived the 6- or 12-week experimental period. Four wounds dehiscence were further stapled without any signs of wound infection. No rabbit died during the experimental period. At euthanasia, no clinical signs of inflammation or adverse tissue reactions were observed. All implants remained in situ. At baseline, rabbits had a mean weight of 3254.2 ± 199.6 mg. At last follow-up, rabbits had a mean weight of 3901.9 ± 275.0 mg. The mean weight difference from baseline was + 647.7 mg (P < 0.0001).

Result syntheses

The overall OIC of the ceramic group was greater at 6 weeks compared to the titanium implants (P = 0.0001). The other endpoints of interest were similar between the two implants at both follow-up times (P ≥ 0.05). No difference was found in BIC at 6- and 12-weeks. The results of the quantitative analyses are shown in detail in Table 1. Figures 3 and 4 show an overview at 1 × magnification of the implants at six and 12 weeks, respectively. Figures 5, 6, 7 and 8 show respectively an overview at 42 × , 140 × , 300 × , 400 × magnification of the implants at 12 weeks.

Table 1 Comparison of HPOC versus titanium at 6- and 12-weeks follow-up (MD: mean difference)
Fig. 3
figure 3

Titanium (left) and ceramic (right) implants at 6 weeks (magnification: 1x). Toluidine blue staining

Fig. 4
figure 4

Titanium (left) and ceramic (right) implants at 12 weeks (magnification: 1x). Toluidine blue staining

Fig. 5
figure 5

Titanium (left) and ceramic (right) implants at 12 weeks (magnification: 42x). Toluidine blue staining

Fig. 6
figure 6

Titanium (left) and ceramic (right) implants at 12 weeks (magnification: 140x). Toluidine blue staining

Fig. 7
figure 7

Titanium (left) and ceramic (right) implants at 12 weeks (magnification: 300x). Toluidine blue staining

Fig. 8
figure 8

Titanium (left) and ceramic (right) implants at 12 weeks (magnification: 400x). Toluidine blue staining


The present study investigated the integration potential of HPOC implants, and then compared in vivo to titanium implants at 6 and 12 weeks. HPOC implants promote similar osteointegration to commercial titanium implants in rabbits. HPOC implants demonstrated greater osteoid implant contact at 6 weeks compared to the titanium implants, with no difference at 12 weeks. The percentage of bone implant contact of HPOC implants was similar to the titanium implants. No bone necrosis, resorption, nor inflammation was observed.

Bone is a dynamic tissue which undergoes continuous modifications and adaptations. For end stage degenerative or traumatic bony ailments, permanent or temporary implants are commonly used to restore bony function and quality of life. In the case of permanent implants (e.g. arthroplasty) the integration of the implant to the surrounding bone is crucial to ensure its longevity.

Recently, implants coating has attracted much interest. Titanium alloys may be responsible of hypersensitivity reactions, which may compromise implant longevity [33,34,35,36,37,38]. When low-grade infection and other mechanical problems have been excluded, symptoms such as pruritus, pain, effusion, erythema, hypersensitivity reactions should be taken into consideration [39]. Ions released by corrosion of metallic wear debris may impair ossification and metal particles can be found in the soft tissues surrounding the implant [40]. Particles and ions may become clinically relevant for sensitive patients. According to the 2016 Australian Arthroplasty Register, approximately 2% of revision TKAs are attributed to metal-related pathology [41]. In selected patients with hypersensitivity, non-metallic implant solution as possible savage revision is limited with unpredictable results [42].

Current researches to develop alternative to the metal alloys are ongoing. In this context, ceramics are attracting growing interest and broad researches. Implant coating aims to optimize the biological properties of the surface to improve ossification. Ceramics are biologically inert, and consequently do not promote implant ossification. However, ceramics have high hardness and wear resistance, light weight, outstanding resistance to creep and compressive stress, avoiding imaging artefacts [12,13,14]. The biological inactivity of ceramics also prevents to systemic reactions to ceramic wear debris and aseptic osteolysis. Therefore, following the development of novel coating methodologies, ceramic implants have triggered renewed interest [15, 16, 43, 44].

Several coating process to functionalise the surface of ceramics have been developed with promising pre-clinical and clinical results [45,46,47,48,49,50]. Previous studies conducted in rabbit models used heterogeneous coating methodologies, follow-up, analyses, and implantation sites (Table 2). The current evidence on the clinical applications of ceramics is still limited, and translational studies are required to clarify the best coating process.

Table 2 Previous studies conducted on rabbit models investigating ceramic coating methodologies

The current evidence on the clinical application of HPOC is limited. Alumina ceramic for talar replacement has been developed over the past 20 years as an alternative to ankle arthrodesis [59]. In 2015, Tanighuki et al. [17] published their results on 55 total talar replacements using customised HPOC, with improvement in range of motion and patient reported outcome measures [17]. Moreover, all patients returned to their activities of daily living with no complication [17]. Several studies investigated HPOC implants for total knee arthroplasty. Most studies used an alumina [18,19,20,21] or a mixed alumina/zirconia [22,23,24] femoral component and metal tibial component.

Few studies investigated the clinical outcomes of a fully alumina [60] or mixed alumina/zirconia [24] total knee implant. Clinical trials indicated that HPOC implants for total knee arthroplasty performed as well as conventional metallic components in improving patient reported outcome measures (PROMs) or inducing complications. In a recent systematic review investigating the efficacy and safety of HPOC implants for total knee arthroplasty in 14 clinical studies, wear and breakage of the prosthesis only occurred in three knees after following up for 18.1 years and in 3 patients after a minimum follow-up of 5 years, respectively [61]. The overall estimate of the rate of revision was 0.03% [61]. Despite the limited use of ceramic knee implants worldwide, and considering the advanced tribological features of the ceramic components, these components demonstrated a promising role in knee implant surgery.

This study has several limitations. The assessors (pathologist and surgeon) were not blinded to the nature of the implant, potentially increasing the risk of detection and performance biases and overestimating the results. A formal mechanical test to prove implant stability (e.g. pull-out torque test) was not conducted. However, previous reports demonstrated a definite association between pull-out torque test and histomorphometry [62,63,64,65]. The absence of physiological load on the prostheses also impairs the validity of the present conclusion, and clinical studies should be performed. Rabbits, being reproducible, low cost, and easy to handle, are commonly used as animal model. However, between species differences exist, and must be considered in clinical translation. Current evidence could benefit of longer follow-up investigation. The results of the present study should encourage further translational studies to verify the ossification potential of ceramics in a clinical setting. Biomaterial research underlined that is possible to design and develop new bone implants with geometry, and chemical characteristics able to improve bone in growth and prevent infection. Two time points (6 and 12 weeks) were used to evaluate osteointegration. In the current literature, heterogeneous time points for analysis of implant osteointegration are reported. Though bone can be already observed at one week after implantation, proper bone remodelling starts between 6 and 12 weeks with primary and secondary osteons forming compact bone [66, 67]. Though implant roughness is a key parameter for the in vivo performance of a bone integrating insert, this parameter was not analysed in the present investigation, and further studies are required to overcome this limitation. Future studies should improve antibiofilm and antibacterial strategies to the novel materials with complementarity between knowledge and expertise in biology, chemistry, engineering and physics, associating biological models with material sciences and other technologies.


HPOC implants demonstrated a greater osteoid implant contact at 6 weeks compared to the titanium implants, and no difference at 12 weeks. The percentage of osteoid production and bone implant contact of HPOC implants was similar to that observed in titanium implants. No bone necrosis, resorption, or inflammation were observed.

Availability of data materials

The data presented in this study are available on request from the corresponding author.



Risedronate calcium phosphate silicate cements


Mesoporous silica


Monocalcium phosphate


Polymerase chain reaction


Parathyroid hormone-related protein






Phosphate-buffered saline


TiO2 nanotube


Hydroxyapatite-TiO2 nanotube


Calcium phosphate ceramic




Tricalcium phosphate 70%


Standard error


95% Confidence interval


Plasma-enhanced chemical vapor deposition

SiOx :

Silicon suboxide


High performance oxide ceramics


Polymethyl methacrylate


  1. Andersen OZ, Offermanns V, Sillassen M, Almtoft KP, Andersen IH, Sorensen S, Jeppesen CS, Kraft DC, Bottiger J, Rasse M, Kloss F, Foss M. Accelerated bone ingrowth by local delivery of strontium from surface functionalized titanium implants. Biomaterials. 2013;34(24):5883–90.

    Article  CAS  Google Scholar 

  2. Albrektsson T, Chrcanovic B, Jacobsson M, Wennerberg A. Osseointegration of implants—a biological and clinical overview. JSM Dent Surg. 2017;2:1–6.

    Google Scholar 

  3. von Wilmowsky C, Moest T, Nkenke E, Stelzle F, Schlegel KA. Implants in bone: part II. Research on implant osseointegration: material testing, mechanical testing, imaging and histoanalytical methods. Oral Maxillofac Surg. 2014;18(4):355–72.

    Article  Google Scholar 

  4. Fernandez-Yague MA, Abbah SA, McNamara L, Zeugolis DI, Pandit A, Biggs MJ. Biomimetic approaches in bone tissue engineering: Integrating biological and physicomechanical strategies. Adv Drug Deliv Rev. 2015;84:1–29.

    Article  CAS  Google Scholar 

  5. Cordova LA, Stresing V, Gobin B, Rosset P, Passuti N, Gouin F, Trichet V, Layrolle P, Heymann D. Orthopaedic implant failure: aseptic implant loosening–the contribution and future challenges of mouse models in translational research. Clin Sci. 2014;127(5):277–93.

    Article  Google Scholar 

  6. Tang K, Deng Z, Wang T, Nie M. Aseptic Loosening after total hip arthroplasty secondary to the disappearing coating? Asian J Surg. 2022;45(1):535–6.

    Article  Google Scholar 

  7. Vladescu A, Mihai Cotrut C, Ak Azem F, Bramowicz M, Pana I, Braic V, Birlik I, Kiss A, Braic M, Abdulgader R, Booysen R, Kulesza S, Monsees TK. Sputtered Si and Mg doped hydroxyapatite for biomedical applications. Biomed Mater. 2018;13(2):025011.

    Article  Google Scholar 

  8. Zhang P, Wang X, Lin Z, Lin H, Zhang Z, Li W, Yang X, Cui J. Ti-based biomedical material modified with TiOx/TiNx duplex bioactivity film via micro-arc oxidation and nitrogen ion implantation. Nanomaterials. 2017.

    Article  Google Scholar 

  9. Duncan WJ, Lee MH, Bae TS, Lee SJ, Gay J, Loch C. Anodisation increases integration of unloaded titanium implants in sheep mandible. Biomed Res Int. 2015;2015:857969.

    Article  CAS  Google Scholar 

  10. Zarone F, Di Mauro MI, Ausiello P, Ruggiero G, Sorrentino R. Current status on lithium disilicate and zirconia: a narrative review. BMC Oral Health. 2019;19(1):134.

    Article  CAS  Google Scholar 

  11. Jung S, Moser MM, Kleinheinz J, Happe A. Biocompatibility of lithium disilicate and zirconium oxide ceramics with different surface topographies for dental implant abutments. Int J Mol Sci. 2021.

    Article  Google Scholar 

  12. Zhang L, Haddouti EM, Welle K, Burger C, Kabir K, Schildberg FA. Local cellular responses to metallic and ceramic nanoparticles from orthopedic joint arthroplasty implants. Int J Nanomedicine. 2020;15:6705–20.

    Article  CAS  Google Scholar 

  13. Trieb K, Glinz J, Reiter M, Kastner J, Senck S. Non-destructive testing of ceramic knee implants using micro-computed tomography. J Arthroplasty. 2019;34(9):2111–7.

    Article  Google Scholar 

  14. Li C, Ai F, Miao X, Liao H, Li F, Liu M, Yu F, Dong L, Li T, Wang X. “The return of ceramic implants”: Rose stem inspired dual layered modification of ceramic scaffolds with improved mechanical and anti-infective properties. Mater Sci Eng C Mater Biol Appl. 2018;93:873–9.

    Article  CAS  Google Scholar 

  15. Taniguchi A, Tanaka Y. An alumina ceramic total talar prosthesis for avascular necrosis of the talus. Foot Ankle Clin. 2019;24(1):163–71.

    Article  Google Scholar 

  16. Pobloth AM, Mersiowsky MJ, Kliemt L, Schell H, Dienelt A, Pfitzner BM, Burgkart R, Detsch R, Wulsten D, Boccaccini AR, Duda GN. Bioactive coating of zirconia toughened alumina ceramic implants improves cancellous osseointegration. Sci Rep. 2019;9(1):16692.

    Article  CAS  Google Scholar 

  17. Taniguchi A, Takakura Y, Tanaka Y, Kurokawa H, Tomiwa K, Matsuda T, Kumai T, Sugimoto K. An alumina ceramic total Talar prosthesis for osteonecrosis of the talus. J Bone Jt Surg Am. 2015;97(16):1348–53.

    Article  Google Scholar 

  18. Nakamura S, Ito H, Nakamura K, Kuriyama S, Furu M, Matsuda S. Long-term durability of ceramic tri-condylar knee implants: a minimum 15-year follow-up. J Arthroplasty. 2017;32(6):1874–9.

    Article  Google Scholar 

  19. Akagi M, Nakamura T, Matsusue Y, Ueo T, Nishijyo K, Ohnishi E. The Bisurface total knee replacement: a unique design for flexion. Four-to-nine-year follow-up study. J Bone Joint Surg Am. 2000;82(11):1626–33.

    Article  CAS  Google Scholar 

  20. Majima T, Yasuda K, Tago H, Aoki Y, Minami A. Clinical results of posterior cruciate ligament retaining TKA with alumina ceramic condylar prosthesis: comparison to Co-Cr alloy prosthesis. Knee Surg Sports Traumatol Arthrosc. 2008;16(2):152–6.

    Article  Google Scholar 

  21. Iida T, Minoda Y, Kadoya Y, Matsui Y, Kobayashi A, Iwaki H, Ikebuchi M, Yoshida T, Nakamura H. Mid-term clinical results of alumina medial pivot total knee arthroplasty. Knee Surg Sports Traumatol Arthrosc. 2012;20(8):1514–9.

    Article  Google Scholar 

  22. Bergschmidt P, Ellenrieder M, Bader R, Kluess D, Finze S, Schwemmer B, Mittelmeier W. Prospective comparative clinical study of ceramic and metallic femoral components for total knee arthroplasty over a five-year follow-up period. Knee. 2016;23(5):871–6.

    Article  Google Scholar 

  23. Bergschmidt P, Bader R, Ganzer D, Hauzeur C, Lohmann CH, Kruger A, Ruther W, Tigani D, Rani N, Esteve JL, Prats FL, Zorzi C, Madonna V, Rigotti S, Benazzo F, Rossi SM, Mittelmeier W. Prospective multi-centre study on a composite ceramic femoral component in total knee arthroplasty: five-year clinical and radiological outcomes. Knee. 2015;22(3):186–91.

    Article  Google Scholar 

  24. Meier E, Gelse K, Trieb K, Pachowsky M, Hennig FF, Mauerer A. First clinical study of a novel complete metal-free ceramic total knee replacement system. J Orthop Surg Res. 2016;11:21.

    Article  CAS  Google Scholar 

  25. Boke F, Giner I, Keller A, Grundmeier G, Fischer H. Plasma-enhanced chemical vapor deposition (PE-CVD) yields better hydrolytical stability of biocompatible SiOx thin films on implant alumina ceramics compared to rapid thermal evaporation physical vapor deposition (PVD). ACS Appl Mater Interfaces. 2016;8(28):17805–16.

    Article  CAS  Google Scholar 

  26. Lauria I, Kramer M, Schroder T, Kant S, Hausmann A, Boke F, Leube R, Telle R, Fischer H. Inkjet printed periodical micropatterns made of inert alumina ceramics induce contact guidance and stimulate osteogenic differentiation of mesenchymal stromal cells. Acta Biomater. 2016;44:85–96.

    Article  CAS  Google Scholar 

  27. Puleo DA, Nanci A. Understanding and controlling the bone-implant interface. Biomaterials. 1999;20:23–4.

    Article  Google Scholar 

  28. Gao X, Fraulob M, Haiat G. Biomechanical behaviours of the bone-implant interface: a review. J R Soc Interface. 2019;16(156):20190259.

    Article  CAS  Google Scholar 

  29. Boke F, Schickle K, Fischer H. Biological activation of inert ceramics: recent advances using tailored self-assembled monolayers on implant ceramic surfaces. Materials. 2014;7(6):4473–92.

    Article  Google Scholar 

  30. Böke F, Giner I, Keller A, Grundmeier G, Fischer H. Plasma-enhanced chemical vapor deposition (PE-CVD) yields better hydrolytical stability of biocompatible SiOx thin films on implant alumina ceramics compared to rapid thermal evaporation physical vapor deposition (PVD). ACS Appl Mater Interfaces. 2016;8:17805–16.

    Article  CAS  Google Scholar 

  31. Vasudev MC, Anderson KD, Bunning TJ, Tsukruk VV, Naik RR. Exploration of plasma-enhanced chemical vapor deposition as a method for thin-film fabrication with biological applications. ACS Appl Mater Interfaces. 2013;5(10):3983–94.

    Article  CAS  Google Scholar 

  32. Li Y, Ren J, Wang B, Lu W, Wang H, Hou W. Development of biobased multilayer films with improved compatibility between polylactic acid-chitosan as a function of transition coating of SiOx. Int J Biol Macromol. 2020;165(Pt A):1258–63.

    Article  CAS  Google Scholar 

  33. Singh R, Lehl G, Hussain AB, Abhang TN, Kulkarni MM, Elagib MFA, Tiwari RVC. Prevalence of titanium hypersensitivity in patients with titanium implants: a systematic review and meta-analysis. J Pharm Bioallied Sci. 2021;13(Suppl 2):S1345–9.

    Article  CAS  Google Scholar 

  34. Sivaraman K, Chopra A, Narayan AI, Balakrishnan D. Is zirconia a viable alternative to titanium for oral implant? A critical review. J Prosthodont Res. 2018;62(2):121–33.

    Article  Google Scholar 

  35. Heitmiller K, Innes M, Zollo V, Sansur C, Goldner R, Powell D, Gaspari AA. Diagnostic dilemmas of titanium hypersensitivity in patients with medical implants: a case series. Eur Ann Allergy Clin Immunol. 2021;53(1):43–6.

    Article  CAS  Google Scholar 

  36. Borgonovo AE, Censi R, Vavassori V, Savio M, Re D. A possible relationship between peri-implantitis, titanium hypersensitivity, and external tooth resorption: metal-free alternative to titanium implants. Case Rep Dent. 2021;2021:8879988.

    Article  Google Scholar 

  37. Wood MM, Warshaw EM. Hypersensitivity reactions to titanium: diagnosis and management. Dermatitis. 2015;26(1):7–25.

    Article  CAS  Google Scholar 

  38. Siddiqi A, Payne AGT, De Silva RK, Duncan WJ. Titanium allergy: could it affect dental implant integration? Clin Oral Implants Res. 2011;22(7):673–80.

    Article  Google Scholar 

  39. Teo WZW, Schalock PC. Metal hypersensitivity reactions to orthopedic implants. Dermatol Ther. 2017;7(1):53–64.

    Article  Google Scholar 

  40. Kretzer JP, Reinders J, Sonntag R, Hagmann S, Streit M, Jeager S, Moradi B. Wear in total knee arthroplasty–just a question of polyethylene?: Metal ion release in total knee arthroplasty. Int Orthop. 2014;38(2):335–40.

    Article  Google Scholar 

  41. Solarino G, Piconi C, De Santis V, Piazzolla A, Moretti B. Ceramic total knee arthroplasty: ready to go? Joints. 2017;5(4):224–8.

    Article  CAS  Google Scholar 

  42. Middleton S, Toms A. Allergy in total knee arthroplasty: a review of the facts. Bone Jt J. 2016;98-B(4):437–41.

    Article  CAS  Google Scholar 

  43. Palmero P, Kern F, Sommer F, Lombardi M, Gadow R, Montanaro L. Issues in nanocomposite ceramic engineering: focus on processing and properties of alumina-based composites. J Appl Biomater Funct Mater. 2014;12(3):113–28.

    Article  CAS  Google Scholar 

  44. Kaur K, Talibi M, Parmar H. Do you know your ceramics? Part 4: alumina. Br Dent J. 2022;232(4):221–3.

    Article  Google Scholar 

  45. Aro HT, Alm JJ, Moritz N, Makinen TJ, Lankinen P. Low BMD affects initial stability and delays stem osseointegration in cementless total hip arthroplasty in women: a 2-year RSA study of 39 patients. Acta Orthop. 2012;83(2):107–14.

    Article  Google Scholar 

  46. Lee YK, Ha YC, Chang BK, Kim KC, Kim TY, Koo KH. Cementless bipolar hemiarthroplasty using a hydroxyapatite-coated long stem for osteoporotic unstable intertrochanteric fractures. J Arthroplasty. 2011;26(4):626–32.

    Article  Google Scholar 

  47. Tao Z, Zhou W, Jiang Y, Wu X, Xu Z, Yang M, Xie J. Effects of strontium-modified calcium phosphate cement combined with bone morphogenetic protein-2 on osteoporotic bone defects healing in rats. J Biomater Appl. 2018;33(1):3–10.

    Article  CAS  Google Scholar 

  48. Tao ZS, Zhou WS, He XW, Liu W, Bai BL, Zhou Q, Huang ZL, Tu KK, Li H, Sun T, Lv YX, Cui W, Yang L. A comparative study of zinc, magnesium, strontium-incorporated hydroxyapatite-coated titanium implants for osseointegration of osteopenic rats. Mater Sci Eng C Mater Biol Appl. 2016;62:226–32.

    Article  CAS  Google Scholar 

  49. Migliorini F, Eschweiler J, Maffulli N, Hildebrand F, Schenker H. Functionalised high-performance oxide ceramics with bone morphogenic protein 2 (BMP-2) induced ossification: an in vivo study. Life. 2022.

    Article  Google Scholar 

  50. Migliorini F, Schenker H, Maffulli N, Hildebrand F, Eschweiler J. Histomorphometry of ossification in functionalised ceramics with tripeptide Arg-Gly-Asp (RGD): an in vivo study. Life. 2022.

    Article  Google Scholar 

  51. Gong T, Chen Y, Zhang Y, Zhang Y, Liu X, Troczynski T, Häfeli UO. Osteogenic and anti-osteoporotic effects of risedronate-added calcium phosphate silicate cement. Biomed Mater. 2016;11:045002.

    Article  Google Scholar 

  52. Lozano D, Trejo CG, Gomez-Barrena E, Manzano M, Doadrio JC, Salinas AJ, Vallet-Regi M, Garcia-Honduvilla N, Esbrit P, Bujan J. Osteostatin-loaded onto mesoporous ceramics improves the early phase of bone regeneration in a rabbit osteopenia model. Acta Biomater. 2012;8(6):2317–23.

    Article  CAS  Google Scholar 

  53. Luo E, Hu J, Bao C, Li Y, Tu Q, Murray D, Chen J. Sustained release of adiponectin improves osteogenesis around hydroxyapatite implants by suppressing osteoclast activity in ovariectomized rabbits. Acta Biomater. 2012;8(2):734–43.

    Article  CAS  Google Scholar 

  54. Plaza JQ, Garzón LB, Gimenez BB, Moraleda BF, Collía F, Rodríguez-Lorenzo LM. Application of calcium phosphates and fibronectin as complementary treatment for osteoporotic bone fractures. Injury. 2016;47:15–21.

    Article  Google Scholar 

  55. Shen X, Ma P, Hu Y, Xu G, Xu K, Chen W, Ran Q, Dai L, Yu Y, Mu C, et al. Alendronate-loaded hydroxyapatite-TiO2 nanotubes for improved bone formation in osteoporotic rabbits. J Mater Chem. 2016;4:1423–36.

    CAS  Google Scholar 

  56. Wu CC, Kuo CL, Fan FY, Yang KC. Strontium-impregnated bioabsorbable composite for osteoporotic fracture fixation. J Biomed Mater Res. 2015;103:3355–63.

    Article  CAS  Google Scholar 

  57. Yu J, Xu L, Li K, Xie N, Xi Y, Wang Y, Zheng X, Chen X, Wang M, Xe Y. Zinc-modified calcium silicate coatings promote osteogenic differentiation through TGF-β/Smad pathway and osseointegration in osteopenic rabbits. Sci Rep. 2017;7:3440.

    Article  Google Scholar 

  58. Gunnella F, Kunisch E, Bungartz M, Maenz S, Horbert V, Xin L, Mika J, Borowski J, Bischoff S, Schubert H, Hortschansky P, Sachse A, Illerhaus B, Gunster J, Bossert J, Jandt KD, Ploger F, Kinne RW, Brinkmann O. Low-dose BMP-2 is sufficient to enhance the bone formation induced by an injectable, PLGA fiber-reinforced, brushite-forming cement in a sheep defect model of lumbar osteopenia. Spine J. 2017;17(11):1699–711.

    Article  Google Scholar 

  59. Tanaka Y, Takakura Y, Kadono K. Alumina ceramic talar body prosthesis for idiopathic aseptic necrosis of the talus. Bioceramic. 2002;21:71–7.

    Google Scholar 

  60. Koshino T, Okamoto R, Takagi T, Yamamoto K, Saito T. Cemented ceramic YMCK total knee arthroplasty in patients with severe rheumatoid arthritis. J Arthroplasty. 2002;17(8):1009–15.

    Article  Google Scholar 

  61. Xiang S, Zhao Y, Li Z, Feng B, Weng X. Clinical outcomes of ceramic femoral prosthesis in total knee arthroplasty: a systematic review. J Orthop Surg Res. 2019;14(1):57.

    Article  Google Scholar 

  62. Ramaswamy Y, Wu C, Dunstan CR, Hewson B, Eindorf T, Anderson GI, Zreiqat H. Sphene ceramics for orthopedic coating applications: an in vitro and in vivo study. Acta Biomater. 2009;5(8):3192–204.

    Article  CAS  Google Scholar 

  63. Zhang W, Wang G, Liu Y, Zhao X, Zou D, Zhu C, Jin Y, Huang Q, Sun J, Liu X, Jiang X, Zreiqat H. The synergistic effect of hierarchical micro/nano-topography and bioactive ions for enhanced osseointegration. Biomaterials. 2013;34(13):3184–95.

    Article  CAS  Google Scholar 

  64. Newman SD, Lotfibakhshaiesh N, O’Donnell M, Walboomers XF, Horwood N, Jansen JA, Amis AA, Cobb JP, Stevens MM. Enhanced osseous implant fixation with strontium-substituted bioactive glass coating. Tissue Eng Part A. 2014;20(13–14):1850–7.

    Article  CAS  Google Scholar 

  65. van Oirschot BA, Alghamdi HS, Narhi TO, Anil S, Al Farraj Aldosari A, van den Beucken JJ, Jansen JA. In vivo evaluation of bioactive glass-based coatings on dental implants in a dog implantation model. Clin Oral Implants Res. 2014;25(1):21–8.

    Article  Google Scholar 

  66. Causey GC, Picha GJ, Price J, Pelletier MH, Wang T, Walsh WR. The effect of a novel pillar surface morphology and material composition demonstrates uniform osseointegration. J Mech Behav Biomed Mater. 2021;123:104775.

    Article  CAS  Google Scholar 

  67. Van Horn MR, Beard R, Wang W, Cunningham BW, Mullinix KP, Allall M, Bucklen BS. Comparison of 3D-printed titanium-alloy, standard titanium-alloy, and PEEK interbody spacers in an ovine model. Spine J. 2021;21(12):2097–103.

    Article  Google Scholar 

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Open Access funding enabled and organized by Projekt DEAL. This research was founded by the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung, BMBF) as part of the Validation of the Technological and Social Innovation Potential of Scientific Research (Validierung des Technologischen und Gesellschaftlichen Innovationspotenzials wissenschaftlicher Forschung) Funding (FZ: 03V0349).

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Conceptualization, MT, JE; investigation, HS, SL, MB; project administration, BR; supervision, FH; writing—original draft, FM and HS. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Filippo Migliorini or Nicola Maffulli.

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This study was conducted according to the Animal Welfare Act of the Federal Republic of Germany. This study was approved by the Federal Office for Nature, Environment and Consumer Protection (Landesamt für Natur, Umwelt und Verbraucherschutz, LANU) of North Rhine-Westphalia, Federal Republic of Germany (Approval ID: 84–02.04.2016.A434).

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Professor Maffulli is the Editor in Chief of the Journal of Orthopaedic Surgery and Research.

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Migliorini, F., Schenker, H., Betsch, M. et al. Silica coated high performance oxide ceramics promote greater ossification than titanium implants: an in vivo study. J Orthop Surg Res 18, 31 (2023).

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  • High performance oxide ceramics
  • Implantology
  • Ossification