Bone cement as a local chemotherapeutic drug delivery carrier in orthopedic oncology: A review

Phull, Sunjeev; Yazdi, Alireza Rahimnejad; Ghert, Michelle; Towler, Mark R.

doi:10.1016/j.jbo.2020.100345

Cited by 19 publications

(18 citation statements)

References 133 publications

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“…Intralesional treatment of low-grade intramedullary chondrosarcoma in the long bones results in average postoperative Musculoskeletal Tumor Society scores of 92% to 94%. 4,10,22 No patient in our study had any apparent discomfort or dysfunction. Therefore, the Musculoskeletal Tumor Society score was not recorded for any patient.…”

Section: Discussionmentioning

confidence: 69%

“…4,8,11,13,15,[19][20][21] Bone cement filling is the most commonly used postoperative method to enhance mechanical stability and increase tumor cytotoxicity. 21,22 However, this method is associated with adverse effects in some patients, such as the risk of postoperative fracture and infections. 11,15,18 In addition, bone cement cannot be absorbed, and the original physiological state of the bone can never be restored.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of bone grafting for treatment of low-grade chondrosarcoma of long bones

Cheon

Park

2021

J Int Med Res

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Objective To retrospectively analyze the biological compatibility and oncologic outcomes of autogenous, allogeneic, or combined bone grafting. Methods From April 2000 to December 2016, 37 patients with histologically confirmed low-grade intramedullary chondrosarcoma of the long bones at Kyungpook National University Hospital were enrolled in this retrospective study. All 37 patients underwent intralesional curettage (with or without cryotherapy) followed by bone grafting. Among the 24 patients who underwent cryotherapy, 13 were treated by prophylactic internal fixation (10 in the femur, 1 in the tibia, and 2 in the humerus). Thirteen patients underwent the same treatment without cryotherapy, whereas 12 did not undergo preventive internal fixation. Results A single intraoperative fracture was managed by plate fixation. One patient who underwent cryotherapy and internal fixation developed a fracture distal to the operation site 25 days after surgery, and this fracture was repaired with a long plate. None of the 37 patients showed any recurrence or metastasis. Conclusions Adequate intralesional curettage (with or without cryosurgery) combined with bone grafting using autogenous and allogeneic bone chips was effective for the treatment of low-grade intramedullary chondrosarcoma. Therefore, prophylactic internal fixation using a plate is recommended in the cryotherapy of definite cortical invasion in weight-bearing bones.

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Section: Discussionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Evaluation of bone grafting for treatment of low-grade chondrosarcoma of long bones

Cheon

Park

2021

J Int Med Res

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“…Larger pores provide an efficient path for drug to elute out of the composite matrix. [40,41] Therefore, since PMMA/15wt%CD-DOX contains the largest pores, it may be most amenable for eventual use in temporary spacer applications. Nevertheless, a greater porosity can weaken the composite, [28] so it is critical to balance the porosity to the desired mechanical properties of the PMMA.…”

Section: Micro-ct Porosity Analysismentioning

confidence: 99%

“…Figure 1 depicts an overview of the analyses carried out in this work. While prior studies have investigated antineoplastic drug-laden PMMA, [30][31][32][33][34][35][36][37][38][39][40] our work is the first to evaluate release kinetics and material/structural properties of DOX-laden PMMA bone cement and to devise a localized adjuvant chemotherapeutic delivery platform to be integrated into temporary spacers for use in the Masquelet technique, offering a potential adjunct to supplement systemic adjuvant chemotherapy. The goal of this study is to evaluate the feasibility of using a PMMA composite chemotherapeutic delivery system for temporary spacer applications for bone reconstruction procedures that is capable of releasing its entire payload and meets mechanical standards.…”

Section: Introductionmentioning

confidence: 99%

PMMA Bone Cement Composite Functions as an Adjuvant Chemotherapeutic Platform for Localized and Multi‐Window Release during Bone Reconstruction

Cyphert

Kanagasegar

Zhang

et al. 2022

Macromolecular Bioscience

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Primary bone tumor resections often result in critical size defects, which then necessitate challenging clinical management approaches to reconstruct. One such intervention is the Masquelet technique, in which poly(methyl methacrylate) (PMMA) bone cement is placed as a spacer temporarily while adjuvant chemotherapeutics are administered systemically. The spacer is later removed and replaced with bone autograft. Local recurrence remains an important and devastating problem, therefore, a system capable of locally delivering chemotherapeutics will present unique advantages. In this work, a refillable chemotherapeutic (doxorubicin, DOX) delivery platform comprised of PMMA bone cement and insoluble 𝜸-cyclodextrin (𝜸-CD) polymeric microparticles is developed and explored towards application as a temporary adjuvant chemotherapeutic spacer. The system is characterized for porosity, mechanical strength, DOX filling and refilling capacity, elution kinetics, and cytotoxicity. Since residual chemotherapeutics can adversely impact bone healing, it is important that virtually all DOX be released from material. Composites containing 15 wt% 𝜸-CD microparticles demonstrate 100% DOX release within 100 days, whereas only 6% DOX is liberated from PMMA with free DOX over same period. Refillable properties of PMMA composite system may find utility for customizing dosing regimens. Findings suggest that PMMA composites can have potential as chemotherapeutic delivery platforms to assist in bone reconstruction.

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“…Finally, they may act as drug delivery systems for antibiotics, anti-inflammatory agents, or anticancer agents. Several studies have reported the addition of classical anticancer drugs to CPCs, to improve their effectiveness and tolerance [3,[6][7][8][9][10]. This local approach also reduces the risk of tumor resurgence in surrounding healthy tissues.…”

Section: Introductionmentioning

confidence: 99%

Controlled release of gallium maltolate complex from injectable phosphocalcic cements

Dupleichs¹,

Limelette²,

Mellier³

et al. 2022

Mater. Res. Express

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Some cancers have tropism for bone: breast, prostate, lung, kidney, and thyroid cancers are the most common. Bone metastases can be treated with surgical resection and the resulting bone defects can be filled with injectable biomaterials. Among these, calcium phosphates may be the biomaterials of choice because of their ability to locally release anticancer active ingredients. Herein, we propose the synthesis of injectable calcium phosphate cement (CPC) loaded with gallium maltolate (GaM). It is an extremely promising anticancer drug with also antibiotic and anti-inflammatory properties. This synthesis was based on commercial cement whose main component was α-tri-calcium phosphate (α-TCP), and the final product obtained after hardening was calcium-deficient apatite (CDA). Two formulations were prepared, containing 3.5% and 7% by mass of GaM (CPC-3.5G and CPC-7G respectively). Powder x-ray diffraction (pXRD), Fourier transform infrared (FTIR) spectroscopy, and magic-angle spinning nuclear magnetic resonance (NMR MAS) 31P analyses showed that the direct incorporation of GaM did not modify the final cement composition. Textural properties, such as setting time, injectability, workability, and cohesiveness, were well preserved or even improved. Additionally, the mechanical strength, although slightly reduced, remained perfectly compatible with surgical use. In vitro kinetics studies of GaM-loaded CPCs showed a controlled release of GaM (49% at 60 days for CPC-3.5G and 58% at 116 days for CPC-7G) following Fick’s law. Raman imaging was used to visualize its diffusion within the cement during in vitro release experiments. Finally, the structural integrity of the gallium complex in the CPC was confirmed using NMR MAS 71Ga.

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Bone cement as a local chemotherapeutic drug delivery carrier in orthopedic oncology: A review

Cited by 19 publications

References 133 publications

Evaluation of bone grafting for treatment of low-grade chondrosarcoma of long bones

Evaluation of bone grafting for treatment of low-grade chondrosarcoma of long bones

PMMA Bone Cement Composite Functions as an Adjuvant Chemotherapeutic Platform for Localized and Multi‐Window Release during Bone Reconstruction

Controlled release of gallium maltolate complex from injectable phosphocalcic cements

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