FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Biomaterials2020; 261; 120302; doi: 10.1016/j.biomaterials.2020.120302

Tough magnesium phosphate-based 3D-printed implants induce bone regeneration in an equine defect model.

Abstract: One of the important challenges in bone tissue engineering is the development of biodegradable bone substitutes with appropriate mechanical and biological properties for the treatment of larger defects and those with complex shapes. Recently, magnesium phosphate (MgP) doped with biologically active ions like strontium (Sr) have shown to significantly enhance bone formation when compared with the standard calcium phosphate-based ceramics. However, such materials can hardly be shaped into large and complex geometries and more importantly lack the adequate mechanical properties for the treatment of load-bearing bone defects. In this study, we have fabricated bone implants through extrusion assisted three-dimensional (3D) printing of MgP ceramics modified with Sr ions (MgPSr) and a medical-grade polycaprolactone (PCL) polymer phase. MgPSr with 30 wt% PCL (MgPSr-PCL30) allowed the printability of relevant size structures (>780 mm) at room temperature with an interconnected macroporosity of approximately 40%. The printing resulted in implants with a compressive strength of 4.3 MPa, which were able to support up to 50 cycles of loading without plastic deformation. Notably, MgPSr-PCL30 scaffolds were able to promote in vitro bone formation in medium without the supplementation with osteo-inducing components. In addition, long-term in vivo performance of the 3D printed scaffolds was investigated in an equine tuber coxae model over 6 months. The micro-CT and histological analysis showed that implantation of MgPSr-PCL30 induced bone regeneration, while no bone formation was observed in the empty defects. Overall, the novel polymer-modified MgP ceramic material and extrusion-based 3D printing process presented here greatly improved the shape ability and load-bearing properties of MgP-based ceramics with simultaneous induction of new bone formation.
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
Get Full Text
Publication Date: 2020-08-23 PubMed ID: 32932172PubMed Central: PMC7116184DOI: 10.1016/j.biomaterials.2020.120302Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article presents a study on magnesium phosphate-based 3D-printed implants, which have been modified with strontium and polycaprolactone, and their capacity to induce bone regeneration, thus showing promise for usage in the treatment of complex and large bone defects.

Research Details and Methodology

In their experiment, the researchers addressed a significant challenge in bone tissue engineering: the necessity for bone substitutes that degrade over time while retaining biological and mechanical functionality, especially in larger, load-bearing bone defects. To achieve this, a novel material was developed:

  • Magnesium phosphate (MgP) ceramics were modified with strontium (Sr) ions, which have been previously noted for their ability to promote bone growth. A biodegradable polymer called polycaprolactone (PCL) was also added to the mixture. The combination material with 30% PCL (referred to as MgPSr-PCL30) was then 3D printed into implant structures.

Results of the 3D Printing Process

The MgPSr-PCL30 material turned out promising due to several factors:

  • The material allowed for the production of large implant structures at room temperature, while maintaining internal macroporosity of about 40%.
  • The resulting implants showed impressive mechanical strength, enduring extensive loading without deformation.
  • This 3D printed scaffolds could promote bone formation in vitro, even without the input of osteo-inducing components typically required for bone growth.

In Vivo Performance

To assess the viability of these new implants, they were tested in a long-term in vivo model:

  • A 6-month study was performed in an equine model, specifically an equine tuber coxae, that is a part of a horse’s hip bone.
  • Micro-CT and histological analyses were utilized to monitor bone growth and reaction to the implant over time.
  • Results showed that these implants were not only compatible with the biological environment, but also successfully induced bone regeneration, unlike empty defects which didn’t cause any bone formation.

Overall Implications

The study has significant implications for bone tissue engineering:

  • The research presents a promising new direction for the production of bone substitutes, particularly those for larger, complex, and load-bearing bone defects, as the MgP-based ceramics significantly improved load-bearing and shaping properties.
  • This 3D printing process also represents a possible means of simplifying the production process for bone implants.
  • The successful in vivo study implies that strontium-modified, MgP-based implants may be viable for further investigation and potential human application in the future.

Cite This Article

APA
Golafshan N, Vorndran E, Zaharievski S, Brommer H, Kadumudi FB, Dolatshahi-Pirouz A, Gbureck U, van Weeren R, Castilho M, Malda J. (2020). Tough magnesium phosphate-based 3D-printed implants induce bone regeneration in an equine defect model. Biomaterials, 261, 120302. https://doi.org/10.1016/j.biomaterials.2020.120302

Publication

Biomaterials
ISSN: 1878-5905
NlmUniqueID: 8100316
Country: Netherlands
Language: English
Volume: 261
Pages: 120302
PII: S0142-9612(20)30548-2

Researcher Affiliations

Golafshan, Nasim
  • Department of Orthopedics, University Medical Center Utrecht, GA, Utrecht, the Netherlands; Regenerative Medicine Utrecht, Utrecht, the Netherlands.
Vorndran, Elke
  • Department for Functional Materials in Medicine and Dentistry, University of Wurzburg, Germany.
Zaharievski, Stefan
  • Department of Orthopedics, University Medical Center Utrecht, GA, Utrecht, the Netherlands; Regenerative Medicine Utrecht, Utrecht, the Netherlands.
Brommer, Harold
  • Department of Equine Sciences, Faculty of Veterinary Sciences, Utrecht University, the Netherlands.
Kadumudi, Firoz Babu
  • Technical University of Denmark, Department of Health Technology, 2800 Kgs, Lyngby, Denmark.
Dolatshahi-Pirouz, Alireza
  • Technical University of Denmark, Department of Health Technology, Center for Intestinal Absorption and Transport of Biopharmaceuticals, 2800 Kgs, Lyngby, Denmark; Department of Regenerative Biomaterials, Radboud University Medical Center, Philips van Leydenlaan 25, Nijmegen, 6525 EX, the Netherlands.
Gbureck, Uwe
  • Department for Functional Materials in Medicine and Dentistry, University of Wurzburg, Germany.
van Weeren, René
  • Department of Equine Sciences, Faculty of Veterinary Sciences, Utrecht University, the Netherlands.
Castilho, Miguel
  • Department of Orthopedics, University Medical Center Utrecht, GA, Utrecht, the Netherlands; Regenerative Medicine Utrecht, Utrecht, the Netherlands; Orthopedic Biomechanics, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, the Netherlands. Electronic address: M.DiasCastilho@umcutrecht.nl.
Malda, Jos
  • Department of Orthopedics, University Medical Center Utrecht, GA, Utrecht, the Netherlands; Regenerative Medicine Utrecht, Utrecht, the Netherlands; Department of Equine Sciences, Faculty of Veterinary Sciences, Utrecht University, the Netherlands.

MeSH Terms

  • Animals
  • Bone Regeneration
  • Horses
  • Magnesium Compounds
  • Phosphates
  • Porosity
  • Printing, Three-Dimensional
  • Tissue Engineering
  • Tissue Scaffolds

Grant Funding

  • 647426 / European Research Council

Conflict of Interest Statement

. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

References

This article includes 50 references
  1. Luo E, Liu H, Zhao Q, Shi B, Chen Q. Dental-craniofacial manifestation and treatment of rare diseases.. Int J Oral Sci 2019 Feb 20;11(1):9.
    doi: 10.1038/s41368-018-0041-ypmc: PMC6381182pubmed: 30783081google scholar: lookup
  2. Jensen T, Jakobsen T, Baas J, Nygaard JV, Dolatshahi-Pirouz A, Hovgaard MB, Foss M, Bünger C, Besenbacher F, Søballe K. Hydroxyapatite nanoparticles in poly-D,L-lactic acid coatings on porous titanium implants conducts bone formation.. J Biomed Mater Res A 2010 Dec 1;95(3):665-72.
    doi: 10.1002/jbm.a.32863pubmed: 20725972google scholar: lookup
  3. Fierz FC, Beckmann F, Huser M, Irsen SH, Leukers B, Witte F, Degistirici O, Andronache A, Thie M, Müller B. The morphology of anisotropic 3D-printed hydroxyapatite scaffolds.. Biomaterials 2008 Oct;29(28):3799-806.
    doi: 10.1016/j.biomaterials.2008.06.012pubmed: 18606446google scholar: lookup
  4. Ke D, Bose S. Effects of pore distribution and chemistry on physical, mechanical, and biological properties of tricalcium phosphate scaffolds by binder-jet 3D printing. Addit Manuf 2018;22:111–117.
    doi: 10.1016/j.addma.2018.04.020google scholar: lookup
  5. Ma Y, Dai H, Huang X, Long Y. 3D printing of bioglass-reinforced β-TCP porous bioceramic scaffolds. J Mater Sci 2019;54:10437–10446.
    doi: 10.1007/s10853-019-03632-3google scholar: lookup
  6. Wang J, Lin C, Gao X, Zheng Z, Lv M, Sun J, Zhang Z. The Enhanced Osteogenesis and Osteointegration of 3-DP PCL Scaffolds via Structural and Functional Optimization Using Collagen Networks. 2018.
    doi: 10.1039/c8ra05615cgoogle scholar: lookup
  7. Chen Y, Xu J, Huang Z, Yu M, Zhang Y, Chen H, Ma Z, Liao H, Hu J. An Innovative Approach for Enhancing Bone Defect Healing Using PLGA Scaffolds Seeded with Extracorporeal-shock-wave-treated Bone Marrow Mesenchymal Stem Cells (BMSCs).. Sci Rep 2017 Mar 8;7:44130.
    doi: 10.1038/srep44130pmc: PMC5341040pubmed: 28272494google scholar: lookup
  8. Jakus AE, Rutz AL, Jordan SW, Kannan A, Mitchell SM, Yun C, Koube KD, Yoo SC, Whiteley HE, Richter CP, Galiano RD, Hsu WK, Stock SR, Hsu EL, Shah RN. Hyperelastic "bone": A highly versatile, growth factor-free, osteoregenerative, scalable, and surgically friendly biomaterial.. Sci Transl Med 2016 Sep 28;8(358):358ra127.
    pubmed: 27683552doi: 10.1126/scitranslmed.aaf7704google scholar: lookup
  9. Rakovsky A, Gotman I, Rabkin E, Gutmanas EY. β-TCP-polylactide composite scaffolds with high strength and enhanced permeability prepared by a modified salt leaching method.. J Mech Behav Biomed Mater 2014 Apr;32:89-98.
    doi: 10.1016/j.jmbbm.2013.12.022pubmed: 24445005google scholar: lookup
  10. Sopyan I, Rahim TA. Porous magnesium-doped biphasic calcium phosphate ceramics prepared via polymeric sponge method. Mater Manuf Process 2012;27:702–706.
    doi: 10.1080/10426914.2011.602787google scholar: lookup
  11. Shazni ZA, Mariatti M, Nurazreena A, Razak KA. Properties of calcium phosphate scaffolds produced by freeze-casting. Procedia Chem 2016;19:174–180.
    doi: 10.1016/j.proche.2016.03.090google scholar: lookup
  12. Chen W, Zhou H, Tang M, Weir MD, Bao C, Xu HH. Gas-foaming calcium phosphate cement scaffold encapsulating human umbilical cord stem cells.. Tissue Eng Part A 2012 Apr;18(7-8):816-27.
    doi: 10.1089/ten.tea.2011.0267pmc: PMC3313611pubmed: 22011243google scholar: lookup
  13. Li T, Zhai D, Ma B, Xue J, Zhao P, Chang J, Gelinsky M, Wu C. 3D Printing of Hot Dog-Like Biomaterials with Hierarchical Architecture and Distinct Bioactivity.. Adv Sci (Weinh) 2019 Oct 2;6(19):1901146.
    doi: 10.1002/advs.201901146pmc: PMC6774059pubmed: 31592134google scholar: lookup
  14. Meininger S, Mandal S, Kumar A, Groll J, Basu B, Gbureck U. Strength reliability and in vitro degradation of three-dimensional powder printed strontium-substituted magnesium phosphate scaffolds.. Acta Biomater 2016 Feb;31:401-411.
    doi: 10.1016/j.actbio.2015.11.050pubmed: 26621692google scholar: lookup
  15. Castilho M, Moseke C, Ewald A, Gbureck U, Groll J, Pires I, Teßmar J, Vorndran E. Direct 3D powder printing of biphasic calcium phosphate scaffolds for substitution of complex bone defects.. Biofabrication 2014 Mar;6(1):015006.
    doi: 10.1088/1758-5082/6/1/015006pubmed: 24429776google scholar: lookup
  16. Castilho M, Rodrigues J, Pires I, Gouveia B, Pereira M, Moseke C, Groll J, Ewald A, Vorndran E. Fabrication of individual alginate-TCP scaffolds for bone tissue engineering by means of powder printing.. Biofabrication 2015 Jan 6;7(1):015004.
    doi: 10.1088/1758-5090/7/1/015004pubmed: 25562119google scholar: lookup
  17. Mohanty S, Alm M, Hemmingsen M, Dolatshahi-Pirouz A, Trifol J, Thomsen P, Dufva M, Wolff A, Emnéus J. 3D Printed Silicone-Hydrogel Scaffold with Enhanced Physicochemical Properties.. Biomacromolecules 2016 Apr 11;17(4):1321-9.
    doi: 10.1021/acs.biomac.5b01722pubmed: 26902925google scholar: lookup
  18. Castilho M, Dias M, Gbureck U, Groll J, Fernandes P, Pires I, Gouveia B, Rodrigues J, Vorndran E. Fabrication of computationally designed scaffolds by low temperature 3D printing.. Biofabrication 2013 Sep;5(3):035012.
    doi: 10.1088/1758-5082/5/3/035012pubmed: 23887064google scholar: lookup
  19. Castilho M, Dias M, Vorndran E, Gbureck U, Fernandes P, Pires I, Gouveia B, Armés H, Pires E, Rodrigues J. Application of a 3D printed customized implant for canine cruciate ligament treatment by tibial tuberosity advancement.. Biofabrication 2014 Jun;6(2):025005.
    doi: 10.1088/1758-5082/6/2/025005pubmed: 24658159google scholar: lookup
  20. Wu C, Fan W, Zhou Y, Luo Y, Gelinsky M, Chang J, Xiao Y. 3D-printing of highly uniform CaSiO 3 ceramic scaffolds: preparation, characterization and in vivo osteogenesis. J Mater Chem 2012;22:12288–12295.
    doi: 10.1039/c2jm30566fgoogle scholar: lookup
  21. Kanter B, Vikman A, Brückner T, Schamel M, Gbureck U, Ignatius A. Bone regeneration capacity of magnesium phosphate cements in a large animal model.. Acta Biomater 2018 Mar 15;69:352-361.
    pubmed: 29409867doi: 10.1016/j.actbio.2018.01.035google scholar: lookup
  22. Kim JA, Lim J, Naren R, Yun HS, Park EK. Effect of the biodegradation rate controlled by pore structures in magnesium phosphate ceramic scaffolds on bone tissue regeneration in vivo.. Acta Biomater 2016 Oct 15;44:155-67.
    doi: 10.1016/j.actbio.2016.08.039pubmed: 27554019google scholar: lookup
  23. Yang X, Xie B, Wang L, Qin Y, Henneman J, Nancollas GH. Influence of Magnesium Ions and Amino Acids on the Nucleation and Growth of Hydroxyapatite. CrystEngComm 2011:1153–1158.
    doi: 10.1039/c0ce00470ggoogle scholar: lookup
  24. Lode A, Heiss C, Knapp G, Thomas J, Nies B, Gelinsky M, Schumacher M. Strontium-modified premixed calcium phosphate cements for the therapy of osteoporotic bone defects.. Acta Biomater 2018 Jan;65:475-485.
    doi: 10.1016/j.actbio.2017.10.036pubmed: 29107056google scholar: lookup
  25. Choudhary S, Halbout P, Alander C, Raisz L, Pilbeam C. Strontium ranelate promotes osteoblastic differentiation and mineralization of murine bone marrow stromal cells: involvement of prostaglandins.. J Bone Miner Res 2007 Jul;22(7):1002-10.
    doi: 10.1359/JBMR.070321pubmed: 17371157google scholar: lookup
  26. Canalis E, Hott M, Deloffre P, Tsouderos Y, Marie PJ. The divalent strontium salt S12911 enhances bone cell replication and bone formation in vitro.. Bone 1996 Jun;18(6):517-23.
    pubmed: 8805991doi: 10.1016/8756-3282(96)00080-4google scholar: lookup
  27. Reichert JC, Wullschleger ME, Cipitria A, Lienau J, Cheng TK, Schütz MA, Duda GN, Nöth U, Eulert J, Hutmacher DW. Custom-made composite scaffolds for segmental defect repair in long bones.. Int Orthop 2011 Aug;35(8):1229-36.
    doi: 10.1007/s00264-010-1146-xpmc: PMC3167439pubmed: 21136053google scholar: lookup
  28. Meininger S, Moseke C, Spatz K, März E, Blum C, Ewald A, Vorndran E. Effect of strontium substitution on the material properties and osteogenic potential of 3D powder printed magnesium phosphate scaffolds.. Mater Sci Eng C Mater Biol Appl 2019 May;98:1145-1158.
    pubmed: 30812998doi: 10.1016/j.msec.2019.01.053google scholar: lookup
  29. Ribeiro A, Blokzijl MM, Levato R, Visser CW, Castilho M, Hennink WE, Vermonden T, Malda J. Assessing bioink shape fidelity to aid material development in 3D bioprinting.. Biofabrication 2017 Nov 30;10(1):014102.
    doi: 10.1088/1758-5090/aa90e2pmc: PMC7116103pubmed: 28976364google scholar: lookup
  30. Doube M, Kłosowski MM, Arganda-Carreras I, Cordelières FP, Dougherty RP, Jackson JS, Schmid B, Hutchinson JR, Shefelbine SJ. BoneJ: Free and extensible bone image analysis in ImageJ.. Bone 2010 Dec;47(6):1076-9.
    doi: 10.1016/j.bone.2010.08.023pmc: PMC3193171pubmed: 20817052google scholar: lookup
  31. Gawlitta D, Benders KE, Visser J, van der Sar AS, Kempen DH, Theyse LF, Malda J, Dhert WJ. Decellularized cartilage-derived matrix as substrate for endochondral bone regeneration.. Tissue Eng Part A 2015 Feb;21(3-4):694-703.
    doi: 10.1089/ten.tea.2014.0117pubmed: 25316202google scholar: lookup
  32. Kimura A, Abe H, Tsuruta S, Chiba S, Fujii-Kuriyama Y, Sekiya T, Morita R, Yoshimura A. Aryl hydrocarbon receptor protects against bacterial infection by promoting macrophage survival and reactive oxygen species production.. Int Immunol 2014 Apr;26(4):209-20.
    doi: 10.1093/intimm/dxt067pubmed: 24343818google scholar: lookup
  33. Dolatshahi-Pirouz A, Nikkhah M, Gaharwar AK, Hashmi B, Guermani E, Aliabadi H, Camci-Unal G, Ferrante T, Foss M, Ingber DE, Khademhosseini A. A combinatorial cell-laden gel microarray for inducing osteogenic differentiation of human mesenchymal stem cells.. Sci Rep 2014 Jan 29;4:3896.
    doi: 10.1038/srep03896pmc: PMC3905276pubmed: 24473466google scholar: lookup
  34. Aparicio SR, Marsden P. A rapid methylene blue-basic fuchsin stain for semi-thin sections of peripheral nerve and other tissues.. J Microsc 1969;89(1):139-41.
    doi: 10.1111/j.1365-2818.1969.tb00659.xpubmed: 4184698google scholar: lookup
  35. Eshraghi S, Das S. Mechanical and microstructural properties of polycaprolactone scaffolds with one-dimensional, two-dimensional, and three-dimensional orthogonally oriented porous architectures produced by selective laser sintering.. Acta Biomater 2010 Jul;6(7):2467-76.
    doi: 10.1016/j.actbio.2010.02.002pmc: PMC2874084pubmed: 20144914google scholar: lookup
  36. Jones AC, Arns CH, Sheppard AP, Hutmacher DW, Milthorpe BK, Knackstedt MA. Assessment of bone ingrowth into porous biomaterials using MICRO-CT.. Biomaterials 2007 May;28(15):2491-504.
    doi: 10.1016/j.biomaterials.2007.01.046pubmed: 17335896google scholar: lookup
  37. Røhl L, Larsen E, Linde F, Odgaard A, Jørgensen J. Tensile and compressive properties of cancellous bone.. J Biomech 1991;24(12):1143-9.
    doi: 10.1016/0021-9290(91)90006-9pubmed: 1769979google scholar: lookup
  38. Kopperdahl DL, Keaveny TM. Yield strain behavior of trabecular bone.. J Biomech 1998 Jul;31(7):601-8.
    doi: 10.1016/S0021-92909800057-8pubmed: 9796682google scholar: lookup
  39. Kim JW, Shin KH, Koh YH, Hah MJ, Moon J, Kim HE. Production of Poly(ε-Caprolactone)/Hydroxyapatite Composite Scaffolds with a Tailored Macro/Micro-Porous Structure, High Mechanical Properties, and Excellent Bioactivity.. Materials (Basel) 2017 Sep 22;10(10).
    doi: 10.3390/ma10101123pmc: PMC5666929pubmed: 28937605google scholar: lookup
  40. Lewis KJ, Frikha-Benayed D, Louie J, Stephen S, Spray DC, Thi MM, Seref-Ferlengez Z, Majeska RJ, Weinbaum S, Schaffler MB. Osteocyte calcium signals encode strain magnitude and loading frequency in vivo.. Proc Natl Acad Sci U S A 2017 Oct 31;114(44):11775-11780.
    doi: 10.1073/pnas.1707863114pmc: PMC5676898pubmed: 29078317google scholar: lookup
  41. Huang B, Caetano G, Vyas C, Blaker JJ, Diver C, Bártolo P. Polymer-Ceramic Composite Scaffolds: The Effect of Hydroxyapatite and β-tri-Calcium Phosphate.. Materials (Basel) 2018 Jan 14;11(1).
    doi: 10.3390/mal1010129pmc: PMC5793627pubmed: 29342890google scholar: lookup
  42. Spencer C, Jonathan P, Janice M, Ralph S. Solvent based 3D printing of hydroxyapatite laden scaffolds for bone tissue engineering. Front Bioeng Biotechnol 2016;4.
    doi: 10.3389/conf.fbioe.2016.01.00145google scholar: lookup
  43. Boanini E, Torricelli P, Fini M, Bigi A. Osteopenic bone cell response to strontium-substituted hydroxyapatite.. J Mater Sci Mater Med 2011 Sep;22(9):2079-88.
    doi: 10.1007/s10856-011-4379-3pubmed: 21691830google scholar: lookup
  44. No YJ, Roohaniesfahani S, Lu Z, Shi J, Zreiqat H. Strontium-doped calcium silicate bioceramic with enhanced in vitro osteogenic properties.. Biomed Mater 2017 Jun 5;12(3):035003.
    doi: 10.1088/1748-605X/aa6987pubmed: 28348275google scholar: lookup
  45. Deng Y, Liu M, Chen X, Wang M, Li X, Xiao Y, Zhang X. Enhanced osteoinductivity of porous biphasic calcium phosphate ceramic beads with high content of strontium-incorporated calcium-deficient hydroxyapatite.. J Mater Chem B 2018 Nov 7;6(41):6572-6584.
    doi: 10.1039/c8tb01637bpubmed: 32254865google scholar: lookup
  46. Ducheyne P, Beight J, Cuckler J, Evans B, Radin S. Effect of calcium phosphate coating characteristics on early post-operative bone tissue ingrowth.. Biomaterials 1990 Oct;11(8):531-40.
    doi: 10.1016/0142-9612(90)90073-ypubmed: 2279054google scholar: lookup
  47. Bioactive ceramic prosthetic coatings. - PubMed - NCBI. [Accessed 8 December 2019].
  48. Sila-Asna M, Bunyaratvej A, Maeda S, Kitaguchi H, Bunyaratavej N. Osteoblast differentiation and bone formation gene expression in strontium-inducing bone marrow mesenchymal stem cell.. Kobe J Med Sci 2007;53(1-2):25-35.
    doi: 10.1016/j.reumae.2011.04.002pubmed: 17579299google scholar: lookup
  49. Akar B, Tatara AM, Sutradhar A, Hsiao HY, Miller M, Cheng MH, Mikos AG, Brey EM. Large Animal Models of an In Vivo Bioreactor for Engineering Vascularized Bone.. Tissue Eng Part B Rev 2018 Aug;24(4):317-325.
    doi: 10.1089/ten.teb.2018.0005pmc: PMC6080121pubmed: 29471732google scholar: lookup
  50. Bohner M, Miron RJ. A proposed mechanism for material-induced heterotopic ossification. Mater Today 2019;22:132–141.
    doi: 10.1016/j.mattod.2018.10.036google scholar: lookup

Citations

This article has been cited 40 times.
  1. Sheng X, Li C, Wang Z, Xu Y, Sun Y, Zhang W, Liu H, Wang J. Advanced applications of strontium-containing biomaterials in bone tissue engineering. Mater Today Bio 2023 Jun;20:100636.
    doi: 10.1016/j.mtbio.2023.100636pubmed: 37441138google scholar: lookup
  2. Bian Y, Hu T, Lv Z, Xu Y, Wang Y, Wang H, Zhu W, Feng B, Liang R, Tan C, Weng X. Bone tissue engineering for treating osteonecrosis of the femoral head. Exploration (Beijing) 2023 Apr;3(2):20210105.
    doi: 10.1002/EXP.20210105pubmed: 37324030google scholar: lookup
  3. Keshavarz M, Alizadeh P, Kadumudi FB, Orive G, Gaharwar AK, Castilho M, Golafshan N, Dolatshahi-Pirouz A. Multi-leveled Nanosilicate Implants Can Facilitate Near-Perfect Bone Healing. ACS Appl Mater Interfaces 2023 May 3;15(17):21476-21495.
    doi: 10.1021/acsami.3c01717pubmed: 37073785google scholar: lookup
  4. Wu Y, Li M, Su H, Chen H, Zhu Y. Up-to-date progress in bioprinting of bone tissue. Int J Bioprint 2023;9(1):628.
    doi: 10.18063/ijb.v9i1.628pubmed: 36636136google scholar: lookup
  5. Wang Z, Liu B, Yin B, Zheng Y, Tian Y, Wen P. Comprehensive review of additively manufactured biodegradable magnesium implants for repairing bone defects from biomechanical and biodegradable perspectives. Front Chem 2022;10:1066103.
    doi: 10.3389/fchem.2022.1066103pubmed: 36523749google scholar: lookup
  6. Tao J, Zhu S, Liao X, Wang Y, Zhou N, Li Z, Wan H, Tang Y, Yang S, Du T, Yang Y, Song J, Liu R. DLP-based bioprinting of void-forming hydrogels for enhanced stem-cell-mediated bone regeneration. Mater Today Bio 2022 Dec 15;17:100487.
    doi: 10.1016/j.mtbio.2022.100487pubmed: 36388461google scholar: lookup
  7. Florea DA, Grumezescu V, Bîrcă AC, Vasile BȘ, Iosif A, Chircov C, Stan MS, Grumezescu AM, Andronescu E, Chifiriuc MC. Bioactive Hydroxyapatite-Magnesium Phosphate Coatings Deposited by MAPLE for Preventing Infection and Promoting Orthopedic Implants Osteointegration. Materials (Basel) 2022 Oct 20;15(20).
    doi: 10.3390/ma15207337pubmed: 36295401google scholar: lookup
  8. Florea DA, Grumezescu V, Bîrcă AC, Vasile BȘ, Mușat M, Chircov C, Stan MS, Grumezescu AM, Andronescu E, Chifiriuc MC. Design, Characterization, and Antibacterial Performance of MAPLE-Deposited Coatings of Magnesium Phosphate-Containing Silver Nanoparticles in Biocompatible Concentrations. Int J Mol Sci 2022 Jul 18;23(14).
    doi: 10.3390/ijms23147910pubmed: 35887261google scholar: lookup
  9. Aytac Z, Dubey N, Daghrery A, Ferreira JA, de Souza Araújo IJ, Castilho M, Malda J, Bottino MC. Innovations in Craniofacial Bone and Periodontal Tissue Engineering - From Electrospinning to Converged Biofabrication. Int Mater Rev 2022;67(4):347-384.
    doi: 10.1080/09506608.2021.1946236pubmed: 35754978google scholar: lookup
  10. Lukin I, Erezuma I, Maeso L, Zarate J, Desimone MF, Al-Tel TH, Dolatshahi-Pirouz A, Orive G. Progress in Gelatin as Biomaterial for Tissue Engineering. Pharmaceutics 2022 May 31;14(6).
    doi: 10.3390/pharmaceutics14061177pubmed: 35745750google scholar: lookup
  11. Wu M, Zhang Y, Wu P, Chen F, Yang Z, Zhang S, Xiao L, Cai L, Zhang C, Chen Y, Deng Z. Mussel-inspired multifunctional surface through promoting osteogenesis and inhibiting osteoclastogenesis to facilitate bone regeneration. NPJ Regen Med 2022 May 13;7(1):29.
    doi: 10.1038/s41536-022-00224-9pubmed: 35562356google scholar: lookup
  12. Carvalho JRG, Conde G, Antonioli ML, Santana CH, Littiere TO, Dias PP, Chinelatto MA, Canola PA, Zara FJ, Ferraz GC. Long-Term Evaluation of Poly(lactic acid) (PLA) Implants in a Horse: An Experimental Pilot Study. Molecules 2021 Nov 29;26(23).
    doi: 10.3390/molecules26237224pubmed: 34885807google scholar: lookup
  13. Zhao Y, Tian C, Wu K, Zhou X, Feng K, Li Z, Wang Z, Han X. Vancomycin-Loaded Polycaprolactone Electrospinning Nanofibers Modulate the Airway Interfaces to Restrain Tracheal Stenosis. Front Bioeng Biotechnol 2021;9:760395.
    doi: 10.3389/fbioe.2021.760395pubmed: 34869271google scholar: lookup
  14. Fuchs A, Kreczy D, Brückner T, Gbureck U, Stahlhut P, Bengel M, Hoess A, Nies B, Bator J, Klammert U, Linz C, Ewald A. Bone regeneration capacity of newly developed spherical magnesium phosphate cement granules. Clin Oral Investig 2022 Mar;26(3):2619-2633.
    doi: 10.1007/s00784-021-04231-wpubmed: 34686919google scholar: lookup
  15. Götz LM, Holeczek K, Groll J, Jüngst T, Gbureck U. Extrusion-Based 3D Printing of Calcium Magnesium Phosphate Cement Pastes for Degradable Bone Implants. Materials (Basel) 2021 Sep 10;14(18).
    doi: 10.3390/ma14185197pubmed: 34576421google scholar: lookup
  16. Kazakova G, Safronova T, Golubchikov D, Shevtsova O, Rau JV. Resorbable Mg(2+)-Containing Phosphates for Bone Tissue Repair. Materials (Basel) 2021 Aug 26;14(17).
    doi: 10.3390/ma14174857pubmed: 34500951google scholar: lookup
  17. Mehrotra D, Kumar S, Mehrotra P, Khanna R, Khanna V, Eggbeer D, Evans P. Patient specific total temporomandibular joint reconstruction: A review of biomaterial, designs, fabrication and outcomes. J Oral Biol Craniofac Res 2021 Apr-Jun;11(2):334-343.
    doi: 10.1016/j.jobcr.2021.02.014pubmed: 33786297google scholar: lookup
  18. Kowalewicz K, Vorndran E, Feichtner F, Waselau AC, Brueckner M, Meyer-Lindenberg A. In-Vivo Degradation Behavior and Osseointegration of 3D Powder-Printed Calcium Magnesium Phosphate Cement Scaffolds. Materials (Basel) 2021 Feb 17;14(4).
    doi: 10.3390/ma14040946pubmed: 33671265google scholar: lookup
  19. Arkin VH, Narendrakumar U, Madhyastha H, Manjubala I. Characterization and In Vitro Evaluations of Injectable Calcium Phosphate Cement Doped with Magnesium and Strontium. ACS Omega 2021 Feb 2;6(4):2477-2486.
    doi: 10.1021/acsomega.0c03927pubmed: 33553866google scholar: lookup
  20. Ribitsch I, Oreff GL, Jenner F. Regenerative Medicine for Equine Musculoskeletal Diseases. Animals (Basel) 2021 Jan 19;11(1).
    doi: 10.3390/ani11010234pubmed: 33477808google scholar: lookup
  21. Han X, Sun M, Chen B, Saiding Q, Zhang J, Song H, Deng L, Wang P, Gong W, Cui W. Lotus seedpod-inspired internal vascularized 3D printed scaffold for bone tissue repair. Bioact Mater 2021 Jun;6(6):1639-1652.
    doi: 10.1016/j.bioactmat.2020.11.019pubmed: 33313444google scholar: lookup
  22. Wang Z, Lv Z, Cai X, Wang Y, Peng B, Xu H, Pang H, Yang X, Xu J, Bian Y, Feng B, Wen P, Zheng Y, Weng X. Sculpting the Future of Bone: The Evolution of Absorbable Materials in Orthopedics. Adv Mater 2026 Feb;38(9):e10848.
    doi: 10.1002/adma.202510848pubmed: 41498178google scholar: lookup
  23. Gałek-Aldridge MS, Willemsen K, Nelissen SH, van der Wal BCH, Malda J, van den Bekerom MPJ, van Noort A. A comparison between a patient-specific bone regenerative implant and the osteochondral allograft procedure in a Hill-Sachs lesion, a cadaveric study. JSES Rev Rep Tech 2026 Feb;6(1):100591.
    doi: 10.1016/j.xrrt.2025.100591pubmed: 41323637google scholar: lookup
  24. Xie C, Li W, Yao X, Wu B, Fang J, Mao R, Yan Y, Meng H, Wu Y, Zhang X, Li R, Zhang J, Duan W, Dai X, Wang X, Ouyang H. Physical and chemical niche of human growth plate for polarized bone development. Nat Commun 2025 Aug 8;16(1):7328.
    doi: 10.1038/s41467-025-62711-zpubmed: 40781081google scholar: lookup
  25. Luo Y, Zhang H, Wang Z, Jiao J, Wang Y, Jiang W, Yu T, Liu H, Guan L, Li M, Wu M. Strategic incorporation of metal ions in bone regenerative scaffolds: multifunctional platforms for advancing osteogenesis. Regen Biomater 2025;12:rbaf068.
    doi: 10.1093/rb/rbaf068pubmed: 40755870google scholar: lookup
  26. Zhang H, Zhang Y, Sheng L, Cao X, Wu C, Song B, Shen Y, Xu Z, Song G, Sun H, Liu Q, Ji X, Jiang M, Li M, Zheng Y. Mechanically robust neuroprotective stent by sequential Mg ions release for ischemic stroke therapy. Nat Commun 2025 Jul 16;16(1):6557.
    doi: 10.1038/s41467-025-61199-xpubmed: 40670341google scholar: lookup
  27. Spauwen L, Pueyo Moliner A, van Veenendaal P, Custers R, Malda J, de Ruijter M. Engineering Anisotropic Mechanical Properties in Large-Scale Fabricated Cartilage Constructs Using Microfiber Reinforcement. Adv Healthc Mater 2025 Jul;14(19):e2501014.
    doi: 10.1002/adhm.202501014pubmed: 40484806google scholar: lookup
  28. Zhu W, Wang W, Yang X, Ran C, Zhang T, Huang S, Yang J, Wang F, Wang H, Wan P, Piao F, Lu F, Shi S, Li Y, Zhang X, Zhao D. Research progress on osteoclast regulation by biodegradable magnesium and its mechanism. Regen Biomater 2025;12:rbaf026.
    doi: 10.1093/rb/rbaf026pubmed: 40395819google scholar: lookup
  29. Joseph A, Uthirapathy V. A Systematic Review of the Contribution of Additive Manufacturing toward Orthopedic Applications. ACS Omega 2024 Nov 5;9(44):44042-44075.
    doi: 10.1021/acsomega.4c04870pubmed: 39524636google scholar: lookup
  30. de Carvalho ABG, Rahimnejad M, Oliveira RLMS, Sikder P, Saavedra GSFA, Bhaduri SB, Gawlitta D, Malda J, Kaigler D, Trichês ES, Bottino MC. Personalized bioceramic grafts for craniomaxillofacial bone regeneration. Int J Oral Sci 2024 Oct 31;16(1):62.
    doi: 10.1038/s41368-024-00327-7pubmed: 39482290google scholar: lookup
  31. Mirzavandi Z, Poursamar SA, Amiri F, Bigham A, Rafienia M. 3D printed polycaprolactone/gelatin/ordered mesoporous calcium magnesium silicate nanocomposite scaffold for bone tissue regeneration. J Mater Sci Mater Med 2024 Sep 30;35(1):58.
    doi: 10.1007/s10856-024-06828-5pubmed: 39348082google scholar: lookup
  32. Malekmohammadi S, Jamshidi R, Sadowska JM, Meng C, Abeykoon C, Akbari M, Gong RH. Stimuli-Responsive Codelivery System-Embedded Polymeric Nanofibers with Synergistic Effects of Growth Factors and Low-Intensity Pulsed Ultrasound to Enhance Osteogenesis Properties. ACS Appl Bio Mater 2024 Jul 15;7(7):4293-4306.
    doi: 10.1021/acsabm.4c00111pubmed: 38917363google scholar: lookup
  33. Martínková M, Zárybnická L, Viani A, Killinger M, Mácová P, Sedláček T, Oralová V, Klepárník K, Humpolíček P. Polyetheretherketone bioactivity induced by farringtonite. Sci Rep 2024 May 28;14(1):12186.
    doi: 10.1038/s41598-024-61941-3pubmed: 38806564google scholar: lookup
  34. Liu Y, Yu L, Chen J, Li S, Wei Z, Guo W. Exploring the Osteogenic Potential of Zinc-Doped Magnesium Phosphate Cement (ZMPC): A Novel Material for Orthopedic Bone Defect Repair. Biomedicines 2024 Feb 1;12(2).
    doi: 10.3390/biomedicines12020344pubmed: 38397946google scholar: lookup
  35. Katebifar S, Arul M, Abdulmalik S, Yu X, Alderete JF, Kumbar SG. NOVEL HIGH-STRENGTH POLYESTER COMPOSITE SCAFFOLDS FOR BONE REGENERATION. Polym Adv Technol 2023 Dec;34(12):3770-3791.
    doi: 10.1002/pat.6178pubmed: 38312483google scholar: lookup
  36. Zhang X, Li Z, Xu X, Liu Z, Hao Y, Yang F, Li X, Zhang N, Hou Y, Zhang X. Huogu injection protects against SONFH by promoting osteogenic differentiation of BMSCs and preventing osteoblast apoptosis. Cell Tissue Res 2024 Jan;395(1):63-79.
    doi: 10.1007/s00441-023-03846-7pubmed: 38040999google scholar: lookup
  37. Volova LT, Kotelnikov GP, Shishkovsky I, Volov DB, Ossina N, Ryabov NA, Komyagin AV, Kim YH, Alekseev DG. 3D Bioprinting of Hyaline Articular Cartilage: Biopolymers, Hydrogels, and Bioinks. Polymers (Basel) 2023 Jun 15;15(12).
    doi: 10.3390/polym15122695pubmed: 37376340google scholar: lookup
  38. Schröter L, Kaiser F, Preißler AL, Wohlfahrt P, Küppers O, Gbureck U, Ignatius A. Ready-To-Use and Rapidly Biodegradable Magnesium Phosphate Bone Cement: In Vivo Evaluation in Sheep. Adv Healthc Mater 2023 Oct;12(26):e2300914.
    doi: 10.1002/adhm.202300914pubmed: 37224104google scholar: lookup
  39. Golafshan N, Castilho M, Daghrery A, Alehosseini M, van de Kemp T, Krikonis K, de Ruijter M, Dal-Fabbro R, Dolatshahi-Pirouz A, Bhaduri SB, Bottino MC, Malda J. Composite Graded Melt Electrowritten Scaffolds for Regeneration of the Periodontal Ligament-to-Bone Interface. ACS Appl Mater Interfaces 2023 Mar 15;15(10):12735-12749.
    doi: 10.1021/acsami.2c21256pubmed: 36854044google scholar: lookup
  40. Golafshan N, Willemsen K, Kadumudi FB, Vorndran E, Dolatshahi-Pirouz A, Weinans H, van der Wal BCH, Malda J, Castilho M. 3D-Printed Regenerative Magnesium Phosphate Implant Ensures Stability and Restoration of Hip Dysplasia. Adv Healthc Mater 2021 Nov;10(21):e2101051.
    doi: 10.1002/adhm.202101051pubmed: 34561956google scholar: lookup
Subscribe to our newsletter
Join 100,129 horse owners like you who receive our email updates on horse health and nutrition.