AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.8595
RESEARCH ARTICLE

A novel tantalum scaffold promoting osteoporotic osseointegration by controlled immune regulation

Aiguo Liu1,2,3,4 Haoran Liao1 Xu Zhang3 Shuang Deng3 Chenxu Wang2,3 Ziwen Zhao3 Guanyin Jiang1,4 Dejian Li3* Jian Hu3* Zhenming Hu1,4*
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1 Department of Orthopedics, The University-Town Hospital of Chongqing Medical University, Chongqing, China
2 Department of Orthopedics, The First Affiliated Hospital of Henan University, Kaifeng, Henan, China
3 Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China
4 Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Submitted: 18 January 2025 | Accepted: 24 February 2025 | Published: 4 March 2025
© 2025 by the Author(s).. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Implant failure due to osteoporosis remains a significant clinical challenge that requires further investigation and resolution. The immunomodulatory properties of bone implant materials are of great significance for the regulation of bone immune microenvironment to promote osteogenesis. This study aims to utilize 3D printing technology to develop a personalized porous tantalum-based MZIF-8-PDA@PTa scaffold and to achieve uniform control of melatonin (MT) and ZIF-8 nano-drug controlled delivery system through polydopamine coating, as well as investigate the effects of osteoporosis on bone regeneration and osseointegration. The MZIF-8-PDA@ PTa scaffold displayed favorable biocompatibility, biodegradability, and mechanical properties, thereby providing an optimal microenvironment for new bone formation. Additionally, the findings indicated that the MZIF-8-PDA@PTa scaffold was capable of recruiting and stimulating M2 macrophage polarization, inhibiting inflammation, and promoting the proliferation and differentiation of bone marrow mesenchymal stem cells. Scaffolds were implanted into the distal femurs of ovariectomized (OVX) rats to ultimately promote bone regeneration and osseointegration in an osteoporotic environment. Moreover, transcriptome sequencing revealed that the MZIF-8-PDA@PTa scaffold was able to promote osteogenic differentiation and mineralization via the P38-MAPK signaling pathway in BMSC cells. Taken together, the MZIF-8-PDA@PTa scaffold enhances bone regeneration and osseointegration in osteoporotic environments through the modulation of macrophage M2 polarization. Consequently, this study offers an alternative approach to creating biomaterials suitable for individuals with osteoporosis.

Graphical abstract
Keywords
Immunomodulation
Macrophage polarization
Melatonin
Osteogenesis
Tantalum
Funding
This work was supported by the Health Industry Clinical Research Project of Shanghai Health Commission (Grant No. 20224Y0393), the Science and Technology Development Fund of Shanghai Pudong New Area (Grant No. PKJ2023-Y09), the Pudong New Area health talent training program (Grant No. 2025PDWSYCQN-06), the Outstanding Leaders Training Program of Pudong Hospital affiliated to Fudan University (Grant No. LX202201, YJRCJJ201908, YJ2023-11), the Project of Key Medical Specialty and Treatment Center of Pudong Hospital of Fudan University (Grant No. Tszb2023-05), the New Quality Clinical Specialty Program of High-end Medical Disciplinary Construction in Shanghai Pudong New Area (2024-PWXZ-14), the Program of Key Medicine of Shanghai Municipal Health Commission (2024ZDXK0031), the joint research project of Pudong Health Committee of Shanghai (Grant No. PW2021D-08), the Health science and technology project of Shanghai Pudong New Area Health Commission(PW2022A-48), and the Project of Key Medical Specialty and Treatment Center of Pudong Hospital of Fudan University (Zdxk2020-02, Zdzk2021-01).
Conflict of interest
The authors declare they have no competing interests.
References
  1. Szczęsny G, Kopec M, Politis DJ, Kowalewski ZL, Łazarski A, Szolc T. A review on biomaterials for orthopaedic surgery and traumatology: from past to present. Materials (Basel). 2022;15(10):3622. doi: 10.3390/ma15103622
  2. Gabay Bass N, Katarivas Levy G, Ron T, et al. Electrochemical behaviour and direct cell viability analysis of hybrid implants made of Ti-6Al-4V lattices infiltrated with a bioabsorbable Zn-based alloy. Metals. 2022;12:1735. doi: 10.3390/met12101735
  3. Lotz EM, Berger MB, Schwartz Z, Boyan BD. Regulation of osteoclasts by osteoblast lineage cells depends on titanium implant surface properties. Acta Biomater. 2018;68:296-307. doi: 10.1016/j.actbio.2017.12.039
  4. Steffi C, Shi Z, Kong CH, Wang W. Modulation of osteoclast interactions with orthopaedic biomaterials. J Funct Biomater. 2018;9:18. doi: 10.3390/jfb9010018
  5. Tang J, Wu Z, Yao X, et al. From bio-inertness to osseointegration and antibacterial activity: a one-step micro-arc oxidation approach for multifunctional Ti implants fabricated by additive manufacturing. Mater Des. 2022;221:110962. doi: 10.1016/j.matdes.2022.110962
  6. Tomizawa T, Ishikawa M, Bello-Irizarry SN, et al. Biofilm producing Staphylococcus epidermidis (RP62A strain) inhibits osseous integration without osteolysis and histopathology in a murine septic implant model. J Orthop Res. 2020;38:852-860. doi: 10.1002/jor.24512
  7. Kruse HV, Lewin WT, Suchowerska N, et al. Plasma immersion ion‐implanted 3D‐printed PEEK bone implants: in vivo sheep study shows strong osseointegration. Plasma Process Polym. 2022;19:2100244. doi: 10.1002/ppap.202100244
  8. Wang W, Chen H, Xiao J, et al. Microenvironment-responsive injectable hydrogel for neuro-vascularized bone regeneration. Mater Today Bio. 2024;29:101369. doi: 10.1016/j.mtbio.2024.101369
  9. Almohandes A, Lund H, Carcuac O, Petzold M, Berglundh T, Abrahamsson I. Accuracy of bone-level assessments following reconstructive surgical treatment of experimental peri-implantitis. Clin Oral Implants Res. 2022;33:433-440. doi: 10.1111/clr.13903
  10. Laux CJ, Hodel SM, Farshad M, Müller DA. Carbon fibre/ polyether ether ketone (CF/PEEK) implants in orthopaedic oncology. World J Surg Oncol. 2018;16:241. doi: 10.1186/s12957-018-1545-9
  11. George M, Naveen SV, Murali MR, Murugan SS, Kumaravel TS, Sathya TN. Review of selected orthopaedic implants for their genotoxicity potential. Int J Sci Technol. 2023;16:2311-2316. doi: 10.17485/IJST/v16i30.george
  12. Gudapati S, Kalyan SR, Santosh KV, et al. Multifarious bone cement and its applications in endodontics – a review. Int J Oral Health Dent. 2022;8(1):9-13. doi: 10.18231/j.ijohd.2022.003
  13. Espiritu J, Meier M, Seitz J-M. The current performance of biodegradable magnesium-based implants in magnetic resonance imaging: a review. Bioact Mater. 2021;6:4360-4367. doi: 10.1016/j.bioactmat.2021.04.012
  14. Song X, Tetik H, Jirakittsonthon T, et al. Biomimetic 3D printing of hierarchical and interconnected porous hydroxyapatite structures with high mechanical strength for bone cell culture. Adv Eng Mater. 2019;21(1):1800678. doi: 10.1002/adem.201800678
  15. Zhang X, He J, Qiao L, et al. 3D printed PCLA scaffold with nano‐hydroxyapatite coating doped green tea EGCG promotes bone growth and inhibits multidrug‐resistant bacteria colonization. Cell Prolif. 2022;55:e13289. doi: 10.1111/cpr.13289
  16. Yang Y, Lei D, Huang S, et al. Elastic 3D‐printed hybrid polymeric scaffold improves cardiac remodeling after myocardial infarction. Adv Healthc Mater. 2019;8:1900065. doi: 10.1002/adhm.201900065
  17. Später T, Mariyanats AO, Syachina MA, et al. In vitro and in vivo analysis of adhesive, anti-inflammatory, and proangiogenic properties of novel 3D printed hyaluronic acid glycidyl methacrylate hydrogel scaffolds for tissue engineering. ACS Biomater Sci Eng. 2020;6:5744-5757. doi: 10.1021/acsbiomaterials.0c00741
  18. He Y, Liu W, Guan L, et al. A 3D-printed PLCL scaffold coated with collagen type I and its biocompatibility. BioMed Res Int. 2018;2018:1-10. doi: 10.1155/2018/5147156
  19. Meesuk L, Suwanprateeb J, Thammarakcharoen F, et al. Osteogenic differentiation and proliferation potentials of human bone marrow and umbilical cord-derived mesenchymal stem cells on the 3D-printed hydroxyapatite scaffolds. Sci Rep. 2022;12:19509. doi: 10.1038/s41598-022-24160-2
  20. Huang Y, Zhang Z, Bi F, et al. Personalized 3D‐printed scaffolds with multiple bioactivities for bioroot regeneration. Adv Healthc Mater. 2023;12:2300625. doi: 10.1002/adhm.202300625
  21. Yun J, Lee J, Ha CW, et al. The effect of 3‐D printed polylactic acid scaffold with and without hyaluronic acid on bone regeneration. J Periodontol. 2022;93:1072-1082. doi: 10.1002/JPER.21-0428
  22. Zhang S, Li R, Song M, Han J, Fan X. Exploration of M2 macrophage membrane as a biotherapeutic agent and strong synergistic therapeutic effects in ischemic stroke. J Control Release. 2025;378:476-489. doi: 10.1016/j.jconrel.2024.11.033
  23. Liu K, Kong L, Cui H, et al. Thymosin α1 reverses oncolytic adenovirus-induced M2 polarization of macrophages to improve antitumor immunity and therapeutic efficacy. Cell Rep Med. 2024;5:101751. doi: 10.1016/j.xcrm.2024.101751
  24. Li J, Luo X, Shiu PH-T, et al. Protective effects of Amauroderma rugosum on dextran sulfate sodium-induced ulcerative colitis through the regulation of macrophage polarization and suppression of oxidative stress. Biomed Pharmacother. 2024;176:116901. doi: 10.1016/j.biopha.2024.116901
  25. Chang J-W, Liu S-C, Lin Y-Y, et al. Nesfatin-1 stimulates CCL2-dependent monocyte migration and M1 macrophage polarization: implications for rheumatoid arthritis therapy. Int J Biol Sci. 2023;19:281-293. doi: 10.7150/ijbs.77987
  26. Cheng Y, Zhong X, Nie X, et al. Glycyrrhetinic acid suppresses breast cancer metastasis by inhibiting M2-like macrophage polarization via activating JNK1/2 signaling. Phytomedicine. 2023;114:154757. doi: 10.1016/j.phymed.2023.154757
  27. Song Y, Lin K, He S, et al. Nano-biphasic calcium phosphate/ polyvinyl alcohol composites with enhanced bioactivity for bone repair via low-temperature three-dimensional printing and loading with platelet-rich fibrin. Int J Nanomedicine. 2018;13:505-523. doi: 10.2147/IJN.S152105
  28. Rossi N, Hadad H, Bejar-Chapa M, et al. Bone marrow stem cells with tissue-engineered scaffolds for large bone segmental defects: a systematic review. Tissue Eng Part B Rev. 2023;29:457-472. doi: 10.1089/ten.teb.2022.0213
  29. Kotta S, Nair A, Alsabeelah N. 3D printing technology in drug delivery: recent progress and application. Curr Pharm Des. 2019;24:5039-5048. doi: 10.2174/1381612825666181206123828
  30. Wang B, Feng C, Pan J, et al. The effect of 3D printing metal materials on osteoporosis treatment. BioMed Res Int. 2021;2021:1-7. doi: 10.1155/2021/9972867
  31. Qian H, Lei T, Lei P, Hu Y. Additively manufactured tantalum implants for repairing bone defects: a systematic review. Tissue Eng Part B Rev. 2021;27:166-180. doi: 10.1089/ten.teb.2020.0134
  32. Liang D, Zhong C, Jiang F, Liao J, Ye H, Ren F. Fabrication of porous tantalum with low elastic modulus and tunable pore size for bone repair. ACS Biomater Sci Eng. 2023;9:1720-1728. doi: 10.1021/acsbiomaterials.2c01239
  33. Zheng S, Zhou C, Yang H, et al. Melatonin accelerates osteoporotic bone defect repair by promoting osteogenesis-angiogenesis coupling. Front Endocrinol (Lausanne). 2022;13:826660. doi: 10.3389/fendo.2022.826660
  34. Ding S, Lin N, Sheng X, et al. Melatonin stabilizes rupture-prone vulnerable plaques via regulating macrophage polarization in a nuclear circadian receptor RORα- dependent manner. J Pineal Res. 2019;67:e12581. doi: 10.1111/jpi.12581
  35. AlNeyadi SS, Amir N, Ghattas MA, et al. Controlled release of pyrimidine compound using polymeric coated ZIF- 8 metal-organic framework as glucagon-like peptide-1 receptor agonist carrier. Molecules 2020;25:4313. doi: 10.3390/molecules25184313
  36. Wang X, Chen X-Z, Alcântara CCJ, et al. MOFBOTS: metal-organic-framework-based biomedical microrobots. Adv Mater. 2019;13:e1901592. doi: 10.1002/adma.201901592
  37. Zou F, Jiang J, Lv F, Xia X, Ma X. Preparation of antibacterial and osteoconductive 3D-printed PLGA/Cu(I)@ZIF- 8 nanocomposite scaffolds for infected bone repair. J Nanobiotechnol. 2020;18:39. doi: 10.1186/s12951-020-00594-6
  38. Niu X, Xiao S, Huang R, et al. ZIF-8-modified hydrogel sequentially delivers angiogenic and osteogenic growth factors to accelerate vascularized bone regeneration. J Control Release. 2024;374:154-170. doi: 10.1016/j.jconrel.2024.08.011
  39. Zhang C, Zhou Z, Liu N, et al. Osteogenic differentiation of 3D-printed porous tantalum with nano-topographic modification for repairing craniofacial bone defects. Front Bioeng Biotechnol. 2023;11:1258030. doi: 10.3389/fbioe.2023.1258030
  40. Karimi A, Khataee A, Vatanpour V, Safarpour M. High-flux PVDF mixed matrix membranes embedded with size-controlled ZIF-8 nanoparticles. Sep Purif Technol. 2019;229:115838. doi: 10.1016/j.seppur.2019.115838
  41. Liu Z, Tan L, Liu X, et al. Zn2+-assisted photothermal therapy for rapid bacteria-killing using biodegradable humic acid encapsulated MOFs. Colloids Surf B Biointerfaces. 2020;188:110781. doi: 10.1016/j.colsurfb.2020.110781
  42. Tan DX, Manchester LC, Reiter RJ, et al. Melatonin directly scavenges hydrogen peroxide: a potentially new metabolic pathway of melatonin biotransformation. Free Radic Biol Med. 2000;29:1177-1185. doi: 10.1016/s0891-5849(00)00435-4
  43. Sun Y, Li Y, Zhang Y, Wang T, Lin K, Liu J. A polydopamine-assisted strontium-substituted apatite coating for titanium promotes osteogenesis and angiogenesis via FAK/MAPK and PI3K/AKT signaling pathways. Mater Sci Eng C. 2021;131:112482. doi: 10.1016/j.msec.2021.112482
  44. Lai M, Chen X, Feng J, Ruan Z, Lin J. Morinda officinalis polysaccharide boosts osteogenic differentiation of bone marrow mesenchymal stem cells by Wnt/β-catenin signaling. Am J Transl Res. 2024;16:4492-4503. doi: 10.62347/WMLI2601
  45. Tian S, Li Y-L, Wang J, et al. Chinese ecliptae herba (Eclipta prostrata (L.) L.) extract and its component wedelolactone enhances osteoblastogenesis of bone marrow mesenchymal stem cells via targeting METTL3-mediated m6A RNA methylation. J Ethnopharmacol. 2023;312: 116433. doi: 10.1016/j.jep.2023.116433
  46. Xiao K, Yang L, Xie W, Gao X, Huang R, Xie M. Bcl-xL mutant promotes cartilage differentiation of BMSCs by upregulating TGF-β/BMP expression levels. Exp Ther Med. 2021;22:736. doi: 10.3892/etm.2021.10168
  47. Kim JM, Yang YS, Park KH, Oh H, Greenblatt MB, Shim JH. The ERK MAPK pathway is essential for skeletal development and homeostasis. Int J Mol Sci. 2019;20(8):1803. doi: 10.3390/ijms20081803
  48. Wang K, Jian M, Chen Y, et al. Soy peptide ameliorate TGF-β1-mediated osteoblast differentiation through Smad and MAPK signaling pathways. J Agric Food Chem. 2024;72:23246-23257. doi: 10.1021/acs.jafc.4c04882
  49. Li X, Gao C, Zhou K, et al. Dendrobine ameliorates glucocorticoid-induced osteoporosis by promoting osteogenesis through JNK/p38 MAPK pathway activation and GR nuclear translocation inhibition. J Agric Food Chem. 2024;72:16739-16748. doi: 10.1021/acs.jafc.4c02798

 

 

 

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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing