Practical strategy to construct anti-osteosarcoma bone substitutes by loading cisplatin into 3D-printed titanium alloy implants using a thermosensitive hydrogel
| Autor: | Zhongjun Liu, Qingguang Wei, Xinhong Lin, Renhua Ni, Zehao Jing, Yufeng Zheng, Daoyang Fan, Wang Jiedong, Teng Zhang, Hong Cai |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
QH301-705.5 0206 medical engineering Biomedical Engineering Urology Context (language use) 02 engineering and technology Bone healing Osseointegration Article Biomaterials Bone conduction In vivo medicine Biology (General) Adverse effect Materials of engineering and construction. Mechanics of materials Cisplatin Osteosarcoma business.industry Orthopaedic implant 021001 nanoscience & nanotechnology medicine.disease 020601 biomedical engineering Hydrogel TA401-492 0210 nano-technology business Local chemotherapy 3D-printed titanium alloy Biotechnology medicine.drug |
| Zdroj: | Bioactive Materials Bioactive Materials, Vol 6, Iss 12, Pp 4542-4557 (2021) |
| ISSN: | 2452-199X |
| Popis: | Surgical resection and perioperative adjuvant chemotherapy-based therapies have improved the prognosis of patients with osteosarcoma; however, intraoperative bone defects, local tumour recurrence, and chemotherapy-induced adverse effects still affect the quality of life of patients. Emerging 3D-printed titanium alloy (Ti6Al4V) implants have advantages over traditional implants in bone repair, including lower elastic modulus, lower stiffness, better bone conduction, more bone in-growth, stronger mechanical interlocking, and lager drug-loading capacity by their inherent porous structure. Here, cisplatin, a clinical first-line anti-osteosarcoma drug, was loaded into Ti6Al4V implants, within a PLGA-PEG-PLGA thermo-sensitive hydrogel, to construct bone substitutes with both anti-osteosarcoma and bone-repair functions. The optimal concentrations of cisplatin (0.8 and 1.6 mg/mL) were first determined in vitro. Thereafter, the anti-tumour effect and biosafety of the cisplatin/hydrogel-loaded implants, as well as their bone-repair potential were evaluated in vivo in tumour-bearing mouse, and bone defect rabbit models, respectively. The loading of cisplatin reduced tumour volume by more than two-thirds (from 641.1 to 201.4 mm3) with negligible organ damage, achieving better anti-tumour effects while avoiding the adverse effects of systemic cisplatin delivery. Although bone repair was hindered by cisplatin loading at 4 weeks, no difference was observed at 8 weeks in the context of implants with versus without cisplatin, indicating acceptable long-term stability of all implants (with 8.48%–10.04% bone in-growth and 16.94%–20.53% osseointegration). Overall, cisplatin/hydrogel-loaded 3D-printed Ti6Al4V implants are safe and effective for treating osteosarcoma-caused bone defects, and should be considered for clinical use. Graphical abstract Image 1 Highlights • Vehiculated within PLGA-PEG-PLGA hydrogel, cisplatin can be conveniently loaded into 3D-printed Ti6Al4V implants. • The cisplatin/hydrogel-loaded implants are safe and show a good anti-tumour potential both in vitro and in vivo. • This strategy has better anti-osteosarcoma effects and fewer side effects than the conventional cisplatin delivery method. • Cisplatin loading does not decrease the bone repair effect of 3D-printed Ti6Al4V implants 8 weeks after surgery. • As the components of the implants are non-toxic, this strategy has great potential for clinical translation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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