Dataset Information

Simvastatin/hydrogel-loaded 3D-printed titanium alloy scaffolds suppress osteosarcoma via TF/NOX2-associated ferroptosis while repairing bone defects.

ABSTRACT: Postoperative anatomical reconstruction and prevention of local recurrence after tumor resection are two vital clinical challenges in osteosarcoma treatment. A three-dimensional (3D)-printed porous Ti6Al4V scaffold (3DTi) is an ideal material for reconstructing critical bone defects with numerous advantages over traditional implants, including a lower elasticity modulus, stronger bone-implant interlock, and larger drug-loading space. Simvastatin is a multitarget drug with anti-tumor and osteogenic potential; however, its efficiency is unsatisfactory when delivered systematically. Here, simvastatin was loaded into a 3DTi using a thermosensitive poly (lactic-co-glycolic) acid (PLGA)-polyethylene glycol (PEG)-PLGA hydrogel as a carrier to exert anti-osteosarcoma and osteogenic effects. Newly constructed simvastatin/hydrogel-loaded 3DTi (Sim-3DTi) was comprehensively appraised, and its newfound anti-osteosarcoma mechanism was explained. Specifically, in a bone defect model of rabbit condyles, Sim-3DTi exhibited enhanced osteogenesis, bone in-growth, and osseointegration compared with 3DTi alone, with greater bone morphogenetic protein 2 expression. In our nude mice model, simvastatin loading reduced tumor volume by 59%-77 % without organic damage, implying good anti-osteosarcoma activity and biosafety. Furthermore, Sim-3DTi induced ferroptosis by upregulating transferrin and nicotinamide adenine dinucleotide phosphate oxidase 2 levels in osteosarcoma both in vivo and in vitro. Sim-3DTi is a promising osteogenic bone substitute for osteosarcoma-related bone defects, with a ferroptosis-mediated anti-osteosarcoma effect.

SUBMITTER: Jing Z

PROVIDER: S-EPMC10689208 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Simvastatin/hydrogel-loaded 3D-printed titanium alloy scaffolds suppress osteosarcoma via TF/NOX2-associated ferroptosis while repairing bone defects.

Jing Zehao Z Yuan Wanqiong W Wang Jiedong J Ni Renhua R Qin Yu Y Mao Zhinan Z Wei Feng F Song Chunli C Zheng Yufeng Y Cai Hong H Liu Zhongjun Z

Bioactive materials 20231117

Postoperative anatomical reconstruction and prevention of local recurrence after tumor resection are two vital clinical challenges in osteosarcoma treatment. A three-dimensional (3D)-printed porous Ti6Al4V scaffold (3DTi) is an ideal material for reconstructing critical bone defects with numerous advantages over traditional implants, including a lower elasticity modulus, stronger bone-implant interlock, and larger drug-loading space. Simvastatin is a multitarget drug with anti-tumor and osteogen ...[more]

PMID: 38045570

Similar Datasets

Project description:Reconstruction of subarticular bone defects is an intractable challenge in orthopedics. The simultaneous repair of cancellous defects, fractures, and cartilage damage is an ideal surgical outcome. 3D printed porous anatomical WE43 (magnesium with 4 wt% yttrium and 3 wt% rare earths) scaffolds have many advantages for repairing such bone defects, including good biocompatibility, appropriate mechanical strength, customizable shape and structure, and biodegradability. In a previous investigation, we successfully enhanced the corrosion resistance of WE43 samples via high temperature oxidation (HTO). In the present study, we explored the feasibility and effectiveness of HTO-treated 3D printed porous anatomical WE43 scaffolds for repairing the cancellous bone defects accompanied by split fractures via in vitro and in vivo experiments. After HTO treatment, a dense oxidation layer mainly composed of Y2O3 and Nd2O3 formed on the surface of scaffolds. In addition, the majority of the grains were equiaxed, with an average grain size of 7.4 μm. Cell and rabbit experiments confirmed the non-cytotoxicity and biocompatibility of the HTO-treated WE43 scaffolds. After the implantation of scaffolds inside bone defects, their porous structures could be maintained for more than 12 weeks without penetration and for more than 6 weeks with penetration. During the postoperative follow-up period for up to 48 weeks, radiographic examinations and histological analysis revealed that abundant bone gradually regenerated along with scaffold degradation, and stable osseointegration formed between new bone and scaffold residues. MRI images further demonstrated no evidence of any obvious damage to the cartilage, ligaments, or menisci, confirming the absence of traumatic osteoarthritis. Moreover, finite element analysis and biomechanical tests further verified that the scaffolds was conducive to a uniform mechanical distribution. In conclusion, applying the HTO-treated 3D printed porous anatomical WE43 scaffolds exhibited favorable repairing effects for subarticular cancellous bone defects, possessing great potential for clinical application.

Project description:A composite comprising Ti and NaCl powders was sintered similar to a three-dimensional (3D)-printed patient-customized artificial bone scaffold. Additionally, a proper microstructure of the mimetic scaffold and the optimum processing parameters for its development were analyzed. The mechanical properties of the metal-based porous-structured framework used as an artificial bone scaffold were an optimum replacement for the human bone. Thus, it was confirmed that patient-customized scaffolds could be manufactured via 3D printing. The 3D-printed mimetic specimens were fabricated by a powder-sintering method using Ti for the metal parts, NaCl as the pore former, and polylactic acid as the biodegradable binder. Scanning electron microscopy (SEM) images showed that pores were formed homogeneously, while X-ray computed tomography confirmed that open pores were generated. The porosity and pore size distribution were measured using a mercury porosimeter, while the flexural strength and flexural elastic modulus were calculated using the three-point bending test. Based on these measurements, a pore-former content of 15 vol % optimized the density and flexural strength to 2.52 g cm-2 and 283 MPa, respectively, similar to those of the actual iliac bone. According to the 3D-printing production method, a selective laser-sintering process was applied for the fabrication of the mimetic specimen, and it was determined that the microstructure and properties similar to those of previous metal specimens could be achieved in the as-prepared specimen. Additionally, a decellularized extracellular matrix (dECM) was used to coat the surfaces and interiors of the specimens for evaluating their biocompatibilities. SEM image analysis indicated that the adipose-derived stem cells grew evenly inside the pores of the coated specimens, as compared with the bulky Ti specimens without the dECM coating. The doubling time at 65% was measured at 72, 75, and 83 h for specimens with pore-former contents of 5, 10, and 15 vol %, respectively. The doubling time without the pore former was 116 h. As compared with the specimens without the pore former (73 h), 15% of the dECM-coated specimens showed a doubling time of 64%, measured at 47 h.

Dataset Information

Simvastatin/hydrogel-loaded 3D-printed titanium alloy scaffolds suppress osteosarcoma via TF/NOX2-associated ferroptosis while repairing bone defects.

Publications

Simvastatin/hydrogel-loaded 3D-printed titanium alloy scaffolds suppress osteosarcoma via TF/NOX2-associated ferroptosis while repairing bone defects.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets