Dataset Information

3D Printed Gene-activated Octacalcium Phosphate Implants for Large Bone Defects Engineering.

ABSTRACT: The aim of the study was the development of three-dimensional (3D) printed gene-activated implants based on octacalcium phosphate (OCP) and plasmid DNA encoding VEGFA. The first objective of the present work involved design and fabrication of gene-activated bone substitutes based on the OCP and plasmid DNA with VEGFA gene using 3D printing approach of ceramic constructs, providing the control of its architectonics compliance to the initial digital models. X-ray diffraction, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and compressive strength analyses were applied to investigate the chemical composition, microstructure, and mechanical properties of the experimental samples. The biodegradation rate and the efficacy of plasmid DNA delivery in vivo were assessed during standard tests with subcutaneous implantation to rodents in the next stage. The final part of the study involved substitution of segmental tibia and mandibular defects in adult pigs with 3D printed gene-activated implants. Biodegradation, osteointegration, and effectiveness of a reparative osteogenesis were evaluated with computerized tomography, SEM, and a histological examination. The combination of gene therapy and 3D printed implants manifested the significant clinical potential for effective bone regeneration in large/critical size defect cases.

SUBMITTER: Bozo IY

PROVIDER: S-EPMC7557339 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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3D Printed Gene-activated Octacalcium Phosphate Implants for Large Bone Defects Engineering.

Bozo Ilya Y IY Deev Roman V RV Smirnov Igor V IV Fedotov Alexander Yu AY Popov Vladimir K VK Mironov Anton V AV Mironova Olga A OA Gerasimenko Alexander Yu AY Komlev Vladimir S VS

International journal of bioprinting 20200603 3

The aim of the study was the development of three-dimensional (3D) printed gene-activated implants based on octacalcium phosphate (OCP) and plasmid DNA encoding <i>VEGFA</i>. The first objective of the present work involved design and fabrication of gene-activated bone substitutes based on the OCP and plasmid DNA with <i>VEGFA</i> gene using 3D printing approach of ceramic constructs, providing the control of its architectonics compliance to the initial digital models. X-ray diffraction, scannin ...[more]

PMID: 33088987

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Project description:ObjectivesTo investigate the feasibility of the 3D printed scaffold for periapical bone defects.MethodsIn this study, antimicrobial peptide KSL-W-loaded PLGA sustainable-release microspheres (KSL-W@PLGA) were firstly prepared followed by assessing the drug release behavior and bacteriostatic ability against Enterococcus faecalis and Porphyromonas gingivalis. After that, we demonstrated that KSL-W@PLGA/collagen (COL)/silk fibroin (SF)/nano-hydroxyapatite (nHA) (COL/SF/nHA) scaffold via 3D-printing technique exhibited significantly good biocompatibility and osteoconductive property. The scaffold was characterized as to pore size, porosity, water absorption expansion rate and mechanical properties. Moreover, MC3T3-E1 cells were seeded into sterile scaffold materials and investigated by CCK-8, SEM and HE staining. In the animal experiment section, we constructed bone defect models of the mandible and evaluated its effect on bone formation. The Japanese white rabbits were killed at 1 and 2 months after surgery, the cone beam computerized tomography (CBCT) and micro-CT scanning, as well as HE and Masson staining analysis were performed on the samples of the operation area, respectively. Data analysis was done using ANOVA and LSD tests. (α = 0.05).ResultsWe observed that the KSL-W@PLGA sustainable-release microspheres prepared in the experiment were uniform in morphology and could gradually release the antimicrobial peptide (KSL-W), which had a long-term antibacterial effect for at least up to 10 days. HE staining and SEM showed that the scaffold had good biocompatibility, which was conducive to the adhesion and proliferation of MC3T3-E1 cells. The porosity and water absorption of the scaffold were (81.96 ± 1.83)% and (458.29 ± 29.79)%, respectively. Histological and radiographic studies showed that the bone healing efficacy of the scaffold was satisfactory.ConclusionsThe KSL-W@PLGA/COL/SF/nHA scaffold possessed good biocompatibility and bone repairing ability, and had potential applications in repairing infected bone defects. Clinical significance The 3D printed scaffold not only has an antibacterial effect, but can also promote bone tissue formation, which provides an alternative therapy option in apical periodontitis.

Project description:BackgroundTreating critically sized defects (CSDs) of bone remains a significant challenge in foot and ankle surgery. Custom 3D-printed implants are being offered to a small but growing subset of patients as a salvage procedure in lieu of traditional alternates such as structural allografts after the patient has failed prior procedures. The long-term outcomes of 3D-printed implants are still unknown and understudied because of the limited number of cases and short follow-up durations. The purpose of this study was to evaluate the outcomes of patients who received custom 3D-printed implants to treat CSDs of the foot and ankle in an attempt to aid surgeons in selecting appropriate surgical candidates.MethodsThis was a retrospective study to assess surgical outcomes of patients who underwent implantation of a custom 3D-printed implant made with medical-grade titanium alloy powder (Ti-6Al-4V) to treat CSDs of the foot and ankle between June 1, 2014, and September 30, 2019. All patients had failed previous nonoperative or operative management before proceeding with treatment with a custom 3D-printed implant. Univariate and multivariate odds ratios (ORs) of a secondary surgery and implant removal were calculated for perioperative variables.ResultsThere were 39 cases of patients who received a custom 3D-printed implant with at least 1 year of follow-up. The mean follow-up time was 27.0 (12-74) months. Thirteen of 39 cases (33.3%) required a secondary surgery and 10 of 39 (25.6%) required removal of the implant because of septic nonunion (6/10) or aseptic nonunion (4/10). The mean time to secondary surgery was 10 months (1-22). Multivariate logistic regression revealed that patients with neuropathy were more likely to require a secondary surgery with an OR of 5.76 (P = .03).ConclusionThis study demonstrated that 74% of patients who received a custom 3D-printed implant for CSDs did not require as subsequent surgery (minimum of 1-year follow-up). Neuropathy was significantly associated with the need for a secondary surgery. This is the largest series to date demonstrating the efficacy of 3D-printed custom titanium implants. As the number of cases using patient-specific 3D-printed titanium implant increases, larger cohorts of patients should be studied to identify other high-risk groups and possible interventions to improve surgical outcomes.Level of evidenceLevel IV, case series.

Project description:The regeneration of bone remains one of the main challenges in the biomedical field, with the need to provide more personalized and multifunctional solutions. The other persistent challenge is related to the local prevention of infections after implantation surgery. To fulfill the first one and provide customized scaffolds with complex geometries, 3D printing is being investigated, with polylactic acid (PLA) as the biomaterial mostly used, given its thermoplastic properties. The 3D printing of PLA in combination with hydroxyapatite (HA) is also under research, to mimic the native mechanical and biological properties, providing more functional scaffolds. Finally, to fulfill the second one, antibacterial drugs locally incorporated into biodegradable scaffolds are also under investigation. This work aims to develop vancomycin-loaded 3D-printed PLA-HA scaffolds offering a dual functionality: local prevention of infections and personalized biodegradable scaffolds with osseointegrative properties. For this, the antibacterial drug vancomycin was incorporated into 3D-printed PLA-HA scaffolds using three loading methodologies: (1) dip coating, (2) drop coating, and (3) direct incorporation in the 3D printing with PLA and HA. A systematic characterization was performed, including release kinetics, Staphylococcus aureus antibacterial/antibiofilm activities and cytocompatibility. The results demonstrated the feasibility of the vancomycin-loaded 3D-printed PLA-HA scaffolds as drug-releasing vehicles with significant antibacterial effects for the three methodologies. In relation to the drug release kinetics, the (1) dip- and (2) drop-coating methodologies achieved burst release (first 60 min) of around 80-90% of the loaded vancomycin, followed by a slower release of the remaining drug for up to 48 h, while the (3) 3D printing presented an extended release beyond 7 days as the polymer degraded. The cytocompatibility of the vancomycin-loaded scaffolds was also confirmed.

Dataset Information

3D Printed Gene-activated Octacalcium Phosphate Implants for Large Bone Defects Engineering.

Publications

3D Printed Gene-activated Octacalcium Phosphate Implants for Large Bone Defects Engineering.

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