Research progress of new multifunctional bone cement in bone tumor therapy_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

SUN Ruilong ¹ , LI Yunfei ² , TIAN Yongzheng ² ,  FAN Bo ²

1. First Clinical Medical School, Gansu University of Chinese Medicine, Lanzhou Gansu, 730030, P. R. China;
2. Department of Spinal Surgery, the 940th Hospital of Joint Logistic Support Force of Chinese PLA, 730050, P. R. China;

Corresponding author：

FAN Bo, Email: borger123@163.com

Keywords：

Bone cement; bone tumor; photothermal therapy; magnetic thermal therapy; chemotherapy; radiotherapy

DOI：

10.7507/1002-1892.202308019

Video：

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Objective The research progress of new multifunctional bone cement in bone tumor therapy in recent years was reviewed, in order to provide help for the future research of anti-tumor bone cement. Methods The related literature on the treatment of bone tumors with new multifunctional bone cement at home and abroad in recent years was extensively reviewed and summarized. Results The new multifunctional bone cements include those with the functions of photothermotherapy, magnetic thermotherapy, chemoradiotherapy, and antibacterial after operation, which are discussed from the aspects of anti-tumor, drug controlled release, and cytotoxicity. Controlled drug release has been achieved in multifunctional bone cements by adjusting heat and pH or incorporating particles such as chitosan oligosaccharides and γ-cyclodextrin. At present, multifunctional bone cement with hyperthermia, radiotherapy, and chemotherapy has effectively inhibited the local recurrence and distant metastasis of bone tumors. Broadening the application of bone cement for photothermal and magnetic thermal therapy to deeper bone tumors, investigating more precise controlled release of drug-loaded bone cement, and introducing nanoparticles with both thermal conversion and intrinsic enzymatic activities into bone cement for synergistic anti-tumor therapy are promising research directions. Conclusion The new multifunctional bone cement inhibits bone tumor cells, promotes new bone formation in bone defects, and prevents incision infection after tumor resection. Certain progress has been made in anti-tumor, antibacterial, drug-controlled release, and reduction of cytotoxicity. Expanding the deeper application range of the new multifunctional bone cement, verifying the safety in clinical application, and focusing on the individualized treatment of the new multifunctional bone cement are the problems that need to be solved in the future.

Citation： SUN Ruilong, LI Yunfei, TIAN Yongzheng, FAN Bo. Research progress of new multifunctional bone cement in bone tumor therapy. Chinese Journal of Reparative and Reconstructive Surgery, 2023, 37(11): 1444-1450. doi: 10.7507/1002-1892.202308019 Copy

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3.	Vaishya R, Chauhan M, Vaish A. Bone cement. J Clin Orthop Trauma, 2013, 4(4): 157-163.
4.	Baroud G, Swanson T, Steffen T. Setting properties of four acrylic and two calcium-phosphate cements used in vertebroplasty. J Long Term Eff Med Implants, 2006, 16(1): 51-59.
5.	Frazer RQ, Byron RT, Osborne PB, et al. PMMA: an essential material in medicine and dentistry. J Long Term Eff Med Implants, 2005, 15(6): 629-639.
6.	Szczęsny G, Kopec M, Politis DJ, et al. A review on biomaterials for orthopaedic surgery and traumatology: From past to present. Materials (Basel), 2022, 15(10): 3622.
7.	Yang H, Zou J. Filling materials used in kyphoplasty and vertebroplasty for vertebral compression fracture: a literature review. Artif Cells Blood Substit Immobil Biotechnol, 2011, 39(2): 87-91.
8.	Gao M, Feng K, Zhang X, et al. Nanoassembly with self-regulated magnetic thermal therapy and controlled immuno-modulating agent release for improved immune response. J Control Release, 2023, 357: 40-51.
9.	Pang S, Kapur A, Zhou K, et al. Nanoparticle-assisted, image-guided laser interstitial thermal therapy for cancer treatment. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2022, 14(5): e1826.
10.	Takegami K, Sano T, Wakabayashi H, et al. New ferromagnetic bone cement for local hyperthermia. J Biomed Mater Res, 1998, 43(2): 210-214.
11.	Yan F, Liu Z, Zhang T, et al. Biphasic injectable bone cement with Fe₃O₄/GO nanocomposites for the minimally invasive treatment of tumor-induced bone destruction. ACS Biomater Sci Eng, 2019, 5(11): 5833-5843.
12.	Ren B, Han Z, Li W, et al. Feasibility study of a novel magnetic bone cement for the treatment of bone metastases. Life (Basel), 2022, 12(9): 1342.
13.	Yu X, Yang T, Liu R, et al. Simultaneous enhancement of magnetothermal and photothermal responses by Zn, Co Co-doped ferrite nanoparticles. Small, 2022, 18(52): e2205037.
14.	Luo Y, Wei X, Wan Y, et al. 3D printing of hydrogel scaffolds for future application in photothermal therapy of breast cancer and tissue repair. Acta Biomater, 2019, 92: 37-47.
15.	Chen H, Yao Y. Progress of biomaterials for bone tumor therapy. J Biomater Appl, 2022, 36(6): 945-955.
16.	Heymann MF, Schiavone K, Heymann D. Bone sarcomas in the immunotherapy era. Br J Pharmacol, 2021, 178(9): 1955-1972.
17.	Kong C, Chen X. Combined photodynamic and photothermal therapy and immunotherapy for cancer treatment: A review. Int J Nanomedicine, 2022, 17: 6427-6446.
18.	Chen Q, Wang C, Zhang X, et al. In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment. Nat Nanotechnol, 2019, 14(1): 89-97.
19.	Wen M, Ouyang J, Wei C, et al. Artificial enzyme catalyzed cascade reactions: Antitumor immunotherapy reinforced by NIR-Ⅱ light. Angew Chem Int Ed Engl, 2019, 58(48): 17425-17432.
20.	Xu C, Ma B, Peng J, et al. Tricalcium silicate/graphene oxide bone cement with photothermal properties for tumor ablation. J Mater Chem B, 2019, 7(17): 2808-2818.
21.	Qu Y, Zhuang H, Zhang M, et al. Bone cements for therapy and regeneration for minimally invasive treatment of neoplastic bone defects. J Mater Chem B, 2021, 9(21): 4355-4364.
22.	Quadros M, Momin M, Verma G. Design strategies and evolving role of biomaterial assisted treatment of osteosarcoma. Mater Sci Eng C Mater Biol Appl, 2021, 121: 111875.
23.	Xu K, Wu X, Cheng Y, et al. A biomimetic nanoenzyme for starvation therapy enhanced photothermal and chemodynamic tumor therapy. Nanoscale, 2020, 12(45): 23159-23165.
24.	Jiang Z, Li J, Chen S, et al. Zoledronate and SPIO dual-targeting nanoparticles loaded with ICG for photothermal therapy of breast cancer tibial metastasis. Sci Rep, 2020, 10(1): 13675.
25.	Yan H, Dong J, Luan X, et al. Ultrathin porous nitrogen-doped carbon-coated CuSe heterostructures for combination cancer therapy of photothermal therapy, photocatalytic therapy, and logic-gated chemotherapy. ACS Appl Mater Interfaces, 2022, 14(50): 56237-56252.
26.	Cheung EC, Vousden KH. The role of ROS in tumour development and progression. Nat Rev Cancer, 2022, 22(5): 280-297.
27.	Zhou Y, Lei H, Wang M, et al. Potent intrinsic bactericidal activity of novel copper telluride nano-grape clusters with facile preparation. Biomater Sci, 2023, 11(5): 1828-1839.
28.	Yao T, Tian Z, Zhang Y, et al. Phosphatase-like activity of porous nanorods of CeO₂ for the highly stabilized dephosphorylation under interferences. ACS Appl Mater Interfaces, 2019, 11(1): 195-201.
29.	Sreeja S, Parameshwar R, Varma PRH, et al. Hierarchically porous osteoinductive poly (hydroxyethyl methacrylate-co-methyl methacrylate) scaffold with sustained doxorubicin delivery for consolidated osteosarcoma treatment and bone defect repair. ACS Biomater Sci Eng, 2021, 7(2): 701-717.
30.	Liang B, Zuo D, Yu K, et al. Multifunctional bone cement for synergistic magnetic hyperthermia ablation and chemotherapy of osteosarcoma. Mater Sci Eng C Mater Biol Appl, 2020, 108: 110460.
31.	Cyphert EL, Kanagasegar N, Zhang N, et al. PMMA bone cement composite functions as an adjuvant chemotherapeutic platform for localized and multi-window release during bone reconstruction. Macromol Biosci, 2022, 22(5): e2100415.
32.	Wang C, Zhang R, He J, et al. Ultrasound-responsive low-dose doxorubicin liposomes trigger mitochondrial DNA release and activate cGAS-STING-mediated antitumour immunity. Nat Commun, 2023, 14(1): 3877.
33.	Tsukimura N, Yamada M, Aita H, et al. N-acetyl cysteine (NAC)-mediated detoxification and functionalization of poly (methyl methacrylate) bone cement. Biomaterials, 2009, 30(20): 3378-3389.
34.	Printezi MI, Kilgallen AB, Bond MJG, et al. Toxicity and efficacy of chronomodulated chemotherapy: a systematic review. Lancet Oncol, 2022, 23(3): e129-e143.
35.	Liao J, Li Y, Li H, et al. Preparation, bioactivity and mechanism of nano-hydroxyapatite/sodium alginate/chitosan bone repair material. J Appl Biomater Funct Mater, 2018, 16(1): 28-35.
36.	Bi YG, Lin ZT, Deng ST. Fabrication and characterization of hydroxyapatite/sodium alginate/chitosan composite microspheres for drug delivery and bone tissue engineering. Mater Sci Eng C Mater Biol Appl, 2019, 100: 576-583.
37.	Phakatkar AH, Shirdar MR, Qi ML, et al. Novel PMMA bone cement nanocomposites containing magnesium phosphate nanosheets and hydroxyapatite nanofibers. Mater Sci Eng C Mater Biol Appl, 2020, 109: 110497.
38.	Nabiyouni M, Brückner T, Zhou H, et al. Magnesium-based bioceramics in orthopedic applications. Acta Biomater, 2018, 66: 23-43.
39.	Morelli T, Fujita K, Redelman-Sidi G, et al. Infections due to dysregulated immunity: an emerging complication of cancer immunotherapy. Thorax, 2022, 77(3): 304-311.
40.	Mukai M, Uchida K, Sugo K, et al. Long-term antibacterial activity of vancomycin from calcium phosphate cement in vivo. Biomed Mater Eng, 2022, 33(1): 41-50.
41.	Morinaga S, Yamamoto N, Tokoro M, et al. Antibacterial effect and biological reaction of calcium phosphate cement impregnated with iodine for use in bone defects. J Biomater Appl, 2023, 37(10): 1716-1723.
42.	Tantavisut S, Leanpolchareanchai J, Wongrakpanich A. Influence of chitosan and chitosan oligosaccharide on dual antibiotic-loaded bone cement: In vitro evaluations. PLoS One, 2022, 17(11): e0276604.
43.	Mou X, Wu Q, Zhang Z, et al. Nanozymes for regenerative medicine. Small Methods, 2022, 6(11): e2200997.
44.	Li X, Li G, Zhang K, et al. Cu-loaded Brushite bone cements with good antibacterial activity and operability. J Biomed Mater Res B Appl Biomater, 2021, 109(6): 877-889.
45.	Anselmetti GC, Manca A, Hirsch J, et al. Percutaneous vertebroplasty in osteoporotic patients: an institutional experience of 1, 634 patients with long-term follow-up. J Vasc Interv Radiol, 2011, 22(12): 1714-1720.
46.	Kaneko TS, Sehgal V, Skinner HB, et al. Radioactive bone cement for the treatment of spinal metastases: a dosimetric analysis of simulated clinical scenarios. Phys Med Biol, 2012, 57(13): 4387-4401.
47.	Keyak JH, Eijansantos ML, Rosecrance KG, et al. A preliminary safety assessment of vertebral augmentation with32P brachytherapy bone cement. Phys Med Biol, 2022, 67(7): 10.1088/1361-6560/ac5e5d.

1. Simpson E, Brown HL. Understanding osteosarcomas. JAAPA, 2018, 31(8): 15-19.
2. Choi JH, Ro JY. The 2020 WHO classification of tumors of bone: An updated review. Adv Anat Pathol, 2021, 28(3): 119-138.
3. Vaishya R, Chauhan M, Vaish A. Bone cement. J Clin Orthop Trauma, 2013, 4(4): 157-163.
4. Baroud G, Swanson T, Steffen T. Setting properties of four acrylic and two calcium-phosphate cements used in vertebroplasty. J Long Term Eff Med Implants, 2006, 16(1): 51-59.
5. Frazer RQ, Byron RT, Osborne PB, et al. PMMA: an essential material in medicine and dentistry. J Long Term Eff Med Implants, 2005, 15(6): 629-639.
6. Szczęsny G, Kopec M, Politis DJ, et al. A review on biomaterials for orthopaedic surgery and traumatology: From past to present. Materials (Basel), 2022, 15(10): 3622.
7. Yang H, Zou J. Filling materials used in kyphoplasty and vertebroplasty for vertebral compression fracture: a literature review. Artif Cells Blood Substit Immobil Biotechnol, 2011, 39(2): 87-91.
8. Gao M, Feng K, Zhang X, et al. Nanoassembly with self-regulated magnetic thermal therapy and controlled immuno-modulating agent release for improved immune response. J Control Release, 2023, 357: 40-51.
9. Pang S, Kapur A, Zhou K, et al. Nanoparticle-assisted, image-guided laser interstitial thermal therapy for cancer treatment. Wiley Interdiscip Rev Nanomed Nanobiotechnol, 2022, 14(5): e1826.
10. Takegami K, Sano T, Wakabayashi H, et al. New ferromagnetic bone cement for local hyperthermia. J Biomed Mater Res, 1998, 43(2): 210-214.
11. Yan F, Liu Z, Zhang T, et al. Biphasic injectable bone cement with Fe₃O₄/GO nanocomposites for the minimally invasive treatment of tumor-induced bone destruction. ACS Biomater Sci Eng, 2019, 5(11): 5833-5843.
12. Ren B, Han Z, Li W, et al. Feasibility study of a novel magnetic bone cement for the treatment of bone metastases. Life (Basel), 2022, 12(9): 1342.
13. Yu X, Yang T, Liu R, et al. Simultaneous enhancement of magnetothermal and photothermal responses by Zn, Co Co-doped ferrite nanoparticles. Small, 2022, 18(52): e2205037.
14. Luo Y, Wei X, Wan Y, et al. 3D printing of hydrogel scaffolds for future application in photothermal therapy of breast cancer and tissue repair. Acta Biomater, 2019, 92: 37-47.
15. Chen H, Yao Y. Progress of biomaterials for bone tumor therapy. J Biomater Appl, 2022, 36(6): 945-955.
16. Heymann MF, Schiavone K, Heymann D. Bone sarcomas in the immunotherapy era. Br J Pharmacol, 2021, 178(9): 1955-1972.
17. Kong C, Chen X. Combined photodynamic and photothermal therapy and immunotherapy for cancer treatment: A review. Int J Nanomedicine, 2022, 17: 6427-6446.
18. Chen Q, Wang C, Zhang X, et al. In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment. Nat Nanotechnol, 2019, 14(1): 89-97.
19. Wen M, Ouyang J, Wei C, et al. Artificial enzyme catalyzed cascade reactions: Antitumor immunotherapy reinforced by NIR-Ⅱ light. Angew Chem Int Ed Engl, 2019, 58(48): 17425-17432.
20. Xu C, Ma B, Peng J, et al. Tricalcium silicate/graphene oxide bone cement with photothermal properties for tumor ablation. J Mater Chem B, 2019, 7(17): 2808-2818.
21. Qu Y, Zhuang H, Zhang M, et al. Bone cements for therapy and regeneration for minimally invasive treatment of neoplastic bone defects. J Mater Chem B, 2021, 9(21): 4355-4364.
22. Quadros M, Momin M, Verma G. Design strategies and evolving role of biomaterial assisted treatment of osteosarcoma. Mater Sci Eng C Mater Biol Appl, 2021, 121: 111875.
23. Xu K, Wu X, Cheng Y, et al. A biomimetic nanoenzyme for starvation therapy enhanced photothermal and chemodynamic tumor therapy. Nanoscale, 2020, 12(45): 23159-23165.
24. Jiang Z, Li J, Chen S, et al. Zoledronate and SPIO dual-targeting nanoparticles loaded with ICG for photothermal therapy of breast cancer tibial metastasis. Sci Rep, 2020, 10(1): 13675.
25. Yan H, Dong J, Luan X, et al. Ultrathin porous nitrogen-doped carbon-coated CuSe heterostructures for combination cancer therapy of photothermal therapy, photocatalytic therapy, and logic-gated chemotherapy. ACS Appl Mater Interfaces, 2022, 14(50): 56237-56252.
26. Cheung EC, Vousden KH. The role of ROS in tumour development and progression. Nat Rev Cancer, 2022, 22(5): 280-297.
27. Zhou Y, Lei H, Wang M, et al. Potent intrinsic bactericidal activity of novel copper telluride nano-grape clusters with facile preparation. Biomater Sci, 2023, 11(5): 1828-1839.
28. Yao T, Tian Z, Zhang Y, et al. Phosphatase-like activity of porous nanorods of CeO₂ for the highly stabilized dephosphorylation under interferences. ACS Appl Mater Interfaces, 2019, 11(1): 195-201.
29. Sreeja S, Parameshwar R, Varma PRH, et al. Hierarchically porous osteoinductive poly (hydroxyethyl methacrylate-co-methyl methacrylate) scaffold with sustained doxorubicin delivery for consolidated osteosarcoma treatment and bone defect repair. ACS Biomater Sci Eng, 2021, 7(2): 701-717.
30. Liang B, Zuo D, Yu K, et al. Multifunctional bone cement for synergistic magnetic hyperthermia ablation and chemotherapy of osteosarcoma. Mater Sci Eng C Mater Biol Appl, 2020, 108: 110460.
31. Cyphert EL, Kanagasegar N, Zhang N, et al. PMMA bone cement composite functions as an adjuvant chemotherapeutic platform for localized and multi-window release during bone reconstruction. Macromol Biosci, 2022, 22(5): e2100415.
32. Wang C, Zhang R, He J, et al. Ultrasound-responsive low-dose doxorubicin liposomes trigger mitochondrial DNA release and activate cGAS-STING-mediated antitumour immunity. Nat Commun, 2023, 14(1): 3877.
33. Tsukimura N, Yamada M, Aita H, et al. N-acetyl cysteine (NAC)-mediated detoxification and functionalization of poly (methyl methacrylate) bone cement. Biomaterials, 2009, 30(20): 3378-3389.
34. Printezi MI, Kilgallen AB, Bond MJG, et al. Toxicity and efficacy of chronomodulated chemotherapy: a systematic review. Lancet Oncol, 2022, 23(3): e129-e143.
35. Liao J, Li Y, Li H, et al. Preparation, bioactivity and mechanism of nano-hydroxyapatite/sodium alginate/chitosan bone repair material. J Appl Biomater Funct Mater, 2018, 16(1): 28-35.
36. Bi YG, Lin ZT, Deng ST. Fabrication and characterization of hydroxyapatite/sodium alginate/chitosan composite microspheres for drug delivery and bone tissue engineering. Mater Sci Eng C Mater Biol Appl, 2019, 100: 576-583.
37. Phakatkar AH, Shirdar MR, Qi ML, et al. Novel PMMA bone cement nanocomposites containing magnesium phosphate nanosheets and hydroxyapatite nanofibers. Mater Sci Eng C Mater Biol Appl, 2020, 109: 110497.
38. Nabiyouni M, Brückner T, Zhou H, et al. Magnesium-based bioceramics in orthopedic applications. Acta Biomater, 2018, 66: 23-43.
39. Morelli T, Fujita K, Redelman-Sidi G, et al. Infections due to dysregulated immunity: an emerging complication of cancer immunotherapy. Thorax, 2022, 77(3): 304-311.
40. Mukai M, Uchida K, Sugo K, et al. Long-term antibacterial activity of vancomycin from calcium phosphate cement in vivo. Biomed Mater Eng, 2022, 33(1): 41-50.
41. Morinaga S, Yamamoto N, Tokoro M, et al. Antibacterial effect and biological reaction of calcium phosphate cement impregnated with iodine for use in bone defects. J Biomater Appl, 2023, 37(10): 1716-1723.
42. Tantavisut S, Leanpolchareanchai J, Wongrakpanich A. Influence of chitosan and chitosan oligosaccharide on dual antibiotic-loaded bone cement: In vitro evaluations. PLoS One, 2022, 17(11): e0276604.
43. Mou X, Wu Q, Zhang Z, et al. Nanozymes for regenerative medicine. Small Methods, 2022, 6(11): e2200997.
44. Li X, Li G, Zhang K, et al. Cu-loaded Brushite bone cements with good antibacterial activity and operability. J Biomed Mater Res B Appl Biomater, 2021, 109(6): 877-889.
45. Anselmetti GC, Manca A, Hirsch J, et al. Percutaneous vertebroplasty in osteoporotic patients: an institutional experience of 1, 634 patients with long-term follow-up. J Vasc Interv Radiol, 2011, 22(12): 1714-1720.
46. Kaneko TS, Sehgal V, Skinner HB, et al. Radioactive bone cement for the treatment of spinal metastases: a dosimetric analysis of simulated clinical scenarios. Phys Med Biol, 2012, 57(13): 4387-4401.
47. Keyak JH, Eijansantos ML, Rosecrance KG, et al. A preliminary safety assessment of vertebral augmentation with32P brachytherapy bone cement. Phys Med Biol, 2022, 67(7): 10.1088/1361-6560/ac5e5d.

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