Electropolishing influence on biocompatibility of additively manufactured Ti-Nb-Ta-Zr: in vivo and in vitro.

Balling defect of the additively manufactured titanium lattice implants easily leads to muscle tissue rejection, which might cause failure of implantation. Electropolishing is widely used in surface polishing of complex components and has potential to deal with the balling defect. However, a clad layer could be formed on the surface of titanium alloy after electropolishing, which may affect the biocompatibility of the metal implants. To manufacture lattice structured ß-type Ti-Ni-Ta-Zr (TNTZ) for bio-medical applications, it is necessary to investigate the impact of electropolishing on material biocompatibility. In this study, animal experiments were conducted to investigate the in vivo biocompatibility of the as-printed TNTZ alloy with or without electropolishing; and proteomics technology was used to elaborate the results. The following conclusions were drawn: (a) a 30% oxalic acid electropolishing treatment was effective in solving balling defects, and ~21 nm amorphous clad layer would be formed on the surface of the material after polishing; (b) the electropolished TNTZ suggested decreased cell cytotoxicity and improved blood biocompatibility as compared to as-printed TNTZ; (c) the amorphous clad layer could make a barrier to prevent Ta and Zr ions from penetrating into the muscle tissue, and could form a good tissue regeneration at the implantation site during 4 weeks, indicating that the electropolished TNTZ has the potential as implants; and (d) the cells attached to the electropolished TNTZ showed higher antioxidant capacity but less proliferation than attached to as-printed TNTZ.

Dose-Response Relationship Between Diltiazem and Tacrolimus and Its Safety in Renal Transplant Recipients.

BACKGROUND: Inhibition of calcineurin inhibitor (CNI) metabolism with diltiazem reduces the dose of tacrolimus required to achieve its therapeutic blood concentration in kidney transplant recipients (KTRs). This cost-savings maneuver is practiced in several countries, including Malaysia, but the actual impacts of diltiazem on tacrolimus blood concentration, dose-response relationship, cost-savings, and safety aspects are unknown. METHODS: This retrospective study was performed on all KTRs ≥18 years of age at our center from January 1, 2006 to December 31, 2015, who were prescribed diltiazem as tacrolimus-sparing agent. Blood tacrolimus trough level (TacC0) and other relevant clinical data for 70 eligible KTRs were reviewed. RESULTS: The dose of 1 mg tacrolimus resulted in a median TacC0 of 0.83 ± 0.52 ng/mL. With the introduction of a 90-mg/d dose diltiazem, there was a significant TacC0 increase to 1.39 ± 1.31 ng/mL/mg tacrolimus (P < .01). A further 90-mg increase in diltiazem to 180 mg/d resulted in a further increase of TacC0 to 1.66 ± 2.58 ng/mL/mg tacrolimus (P = .01). After this, despite a progressive increment of every 90-mg/d dose diltiazem to 270 mg/d and 360 mg/d, there was no further increment in TacC0 (1.44 ± 1.15 ng/mL/mg tacrolimus and 1.24 ± 0.94 ng/mL/mg tacrolimus, respectively [P < .01]). Addition of 180 mg/d diltiazem reduced the required tacrolimus dose to 4 mg/d, resulting in a cost-savings of USD 2045.92 per year (per patient) at our center. Adverse effects reported within 3 months of diltiazem introduction were bradycardia (1.4%) and postural hypotension (1.4%), which resolved after diltiazem dose reduction. CONCLUSION: Coadministration of tacrolimus and diltiazem in KTRs appeared to be safe and resulted in a TacC0 increment until reaching a 180-mg/d total diltiazem dose, at which point it began to decrease. This approach will result in a marked savings in immunosuppression costs among KTRs in Malaysia.

[The preliminary report of a registration clinical trial of proton and heavy ion irradiation].

Objective: To verify the safety and efficacy of IONTRIS particle therapy system (IONTRIS) in clinical implementation. Methods: Between 6.2014 and 8.2014, a total of 35 patients were enrolled into this trial: 31 males and 4 females with a median age of 69 yrs (range 39-80). Ten patients had locally recurrent head and neck tumors after surgery, 4 cases with thoracic malignancies, 1 case with hepatocellular carcinoma, 1 case with retroperitoneal sarcoma, and 19 cases with non-metastatic prostate carcinomas. Phantom dose verification was mandatory for each field before the start of radiation. Results: Twenty-two patients received carbon ion and 13 had proton irradiation. With a median follow-up time of 1 year, all patients were alive. Among the 16 patients with head and neck, thoracic, and abdominal/pelvic tumors, 2, 1, 12, and 1 cases developed complete response, partial response, stable disease, or disease progression, respectively. Progression-free survival rate was 93.8% (15/16). Among the 19 patients with prostate cancer, biological-recurrence free survival was 100%. Particle therapy was well tolerated in all 35 patients. Twenty-five patients (71.4%) experienced 33 grade 1 acute adverse effects, which subsided at 1 year follow-up. Six (17.1%) patients developed grade 1 late adverse effects. No significant change in ECOG or body weight was observed. Conclusions: IONTRIS is safe and effective for clinical use. However, long term follow-up is needed to observe the late toxicity and long term result.

[Biological evaluation of three-dimensional printed co-poly lactic acid/glycolic acid/tri-calcium phosphate scaffold for bone reconstruction].

Objective: To biologically evaluate the three-dimensional(3D) printed co-poly lactic acid/glycolic acid/tri-calcium phosphate(PLGA/TCP) scaffold which could be used for repairing oral and maxillofacial bone defects, and to provide experimental evidence for its further research and clinical application. Methods: PLGA/TCP scaffolds were fabricated using low temperature rapid prototyping technique. Micro-CT and scanning electron microscope(SEM) were used to characterize the surface morphology. MC3T3-E1 cells were seeded onto the scaffold and stained with the rhodamine phalloidin and calcein acetomethoxy. After that, confocal laser scanning microscope was exploited to observe the features and viability of the cells. Moreover, the cells were co-cultured with the extract of PLGA/TCP and complete medium, respectively. The proliferation capability of the cells was assessed by the cell counting kit-8 (CCK-8) on the 1st, 2nd, and 3rd day. The PLGA/TCP scaffolds incorporated with recombinant human bone morphogenetic protein-2(rhBMP-2) of 0, 30, 60 µg(i.e. blank control group, low-dose group and high-dose group) were implanted into the latissimus dorsi muscle of the rats, and 6 weeks later, the samples were harvested to estimate the volume and pattern of new bone. Results: The 3D printed PLGA/TCP scaffold possessed a regular and well-defined porous stereo-structure with porosity of (73±3)%. Micro-CT and SEM showed that pore size were (379±32) and (453±29) µm respectively, and distance between layers were (452± 24) and (415±25) µm, and cylinder diameter were (342±24) and (350±28) µm. It also exhibited excellent cell adhesion and growth ability on the exterior and inner surface through rhodamine phalloidin and calcein acetomethoxy staining. The CCK-8 test demonstrated that the absorbance value of extract group on the 1st and 2nd day(0.51±0.08 and 0.63±0.09) were significantly higher than those in the blank control group(0.39± 0.05 and 0.53±0.05)(P<0.05), while there was no significant difference between the extract group(0.67±0.06) and the blank control group(0.68±0.04)(P>0.05) on the 3rd day. For in vivo test, there was obvious ectopic new bone formation on the PLGA/TCP scaffold incorporated with rhBMP-2, and this was demonstrated using the histological examination and micro-CT. The bone formation in the low-dose group was similar to the shape of the pre-implanted 3D printed scaffold, while much diversity was revealed in the high-dose group duo to over osteogenesis which was validated by the examinations of gross observation, histology and micro-CT. Conclusions: Customized PLGA/TCP scaffolds can be manufactured by 3D printing technique. The scaffold showed an excellent biocompatibility and ectopic osteogenesis when incorporated with rhBMP-2. However, further research is needed to validate it's effect on repairment of the oral and maxillofacial bone defects.