Preclinical evaluation of a 3D-printed hydroxyapatite/poly(lactic-co-glycolic acid) scaffold for ridge augmentation.

BACKGROUND/PURPOSE: Supracrestal ridge augmentation (SRA) is a major challenge for clinicians. This study investigated the efficacy of a 3D-printed (3DP) hydroxyapatite/poly(lactic-co-glycolic acid) (HA/PLGA) scaffold as a potential biologic for SRA. METHODS: Scaffolds that were 5 mm in diameter and 2.5-mm thick with a 1.2-mm diameter through-and-through central hole composed of 90% HA and 10% PLGA were printed using an extrusion-based bioprinter. The HA/PLGA scaffold was fixed with a 1.2-mm titanium mini-implant on the buccal surface of rat mandible (Ti-HPS), and the outcome of SRA were compared with sites treated with a titanium mini-implant alone (control) and a titanium mini-implant covered with deproteinized bovine bone-derived matrix (Ti-DBBM) at 4 and 8 weeks by microcomputed tomography (micro-CT), back-scattered SEM, and histology assessments. RESULTS: The HA/PLGA scaffolds were 2.486 ± 0.082 mm thick with an outer diameter of 4.543 ± 0.057 mm and an inner diameter of 1.089 ± 0.045 mm, and the pore dimensions were 0.48-0.52 mm. There was significantly more mineralized tissue in the Ti-DBBM and Ti-HPS groups than in the control group at both time points. Newly formed bone (NB) was well-integrated with the DBBM and HA/PLGA scaffolds. The framework of the 3DP-HA/PLGA scaffold remained in place, and NB-implant contact (NBIC) was advanced to the middle level in the Ti-HPS group until 8 weeks, whereas dispersion of DBBM with a lower level NBIC was noted in the Ti-DBBM group at both time points. CONCLUSION: The 3DP HA/PLGA scaffold maintains supracrestal space and demonstrates osteoconductivity to facilitate SRA.

Regeneration of critical-sized mandibular defect using a 3D-printed hydroxyapatite-based scaffold: An exploratory study.

BACKGROUND: Three-dimensional (3D) printing has become an available technology to fabricate customized tissue engineering scaffolds with delicate architecture. This exploratory study aimed to evaluate the potential of a 3D-printed hydroxyapatite-based scaffold as a biomaterial for obtaining guided bone regeneration (GBR) in vivo. METHODS: Scaffolds composed of 90% hydroxyapatite and 10% poly(lactic-co-glycolic acid) were printed using a microextrusion process to fit 4 mm diameter and 0.5 mm thick through-and-through osseous defects on the mandibular ramus of rats, with unfilled defects serving as controls. Specimens were analyzed for regeneration-associated gene expression on day 7, and micro-computed tomography (micro-CT) and histology assessments were carried out on day 28. RESULTS: The scaffolds were 3.56 ± 0.43 mm (x-axis) and 4.02 ± 0.44 mm (y-axis) in diameter and 0.542 ± 0.035 mm thick (z-axis), with a mean pore size of 0.420 ± 0.028 × 0.328 ± 0.005 mm2 . Most scaffolds fit the defects well. Type I collagen, VEGF, and Cbfa1 were upregulated in the scaffold-treated defects by day 7. By day 28, de novo osteogenesis and scaffold-tissue integration were evident in the scaffold-treated defects, and entire mineralized tissue, as well as newly formed bone, was significantly promoted, as seen in the micro-CT and histologic analyses. CONCLUSION: The 3D-printed hydroxyapatite-based scaffold showed acceptable dimensional stability and demonstrated favorable osteoregenerative capability that fulfilled the need for GBR.

Core-Shell poly-(D,l-Lactide-co-Glycolide)-chitosan Nanospheres with simvastatin-doxycycline for periodontal and osseous repair.

This study aimed to evaluated the potential of core-shell poly(D,l-lactide-co-glycolide)-chitosan (PLGA-chitosan) nanospheres encapsulating simvastatin (SIM) and doxycycline (DOX) for promoting periodontal and large-sized osseous defects. SIM, and/or DOX were encapsulated in PLGA-chitosan nanospheres using double emulsion technique and were delivered to sites of experimental periodontitis and large-sized mandibular osseous defects of rats for 1-4 weeks. The resultant nanospheres were ~ 200 nm diameter with distinct core-shell structure and released SIM and DOX sustainably for 28 days. DOX and SIM-DOX nanospheres significantly inhibited P. gingivalis and S. sanguinis. In experimental periodontitis sites, SIM-DOX nanospheres significantly down-regulated IL-1b and MMP-8 and significantly reduced bone loss. In mandibular osseous defects, VEGF was up-regulated, and osteogenesis was significantly augmented with SIM nanospheres treatment. In conclusion, core-shell PLGA-chitosan nanospheres released SIM and DOX sustainably. SIM-DOX and SIM nanospheres could be considered to promote the repair of infected periodontal sites and non-infected osseous defects respectively.

Functional Characterization of Waterlogging and Heat Stresses Tolerance Gene Pyruvate decarboxylase 2 from Actinidia deliciosa.

A previous report showed that both Pyruvatedecarboxylase (PDC) genes were significantly upregulated in kiwifruit after waterlogging treatment using Illumina sequencing technology, and that the kiwifruit AdPDC1 gene was required during waterlogging, but might not be required during other environmental stresses. Here, the function of another PDC gene, named AdPDC2, was analyzed. The expression of the AdPDC2 gene was determined using qRT-PCR, and the results showed that the expression levels of AdPDC2 in the reproductive organs were much higher than those in the nutritive organs. Waterlogging, NaCl, and heat could induce the expression of AdPDC2. Overexpression of kiwifruit AdPDC2 in transgenic Arabidopsis enhanced resistance to waterlogging and heat stresses in five-week-old seedlings, but could not enhance resistance to NaCl and mannitol stresses at the seed germination stage and in early seedlings. These results suggested that the kiwifruit AdPDC2 gene may play an important role in waterlogging resistance and heat stresses in kiwifruit.

The ultrasound contrast imaging properties of lipid microbubbles loaded with urokinase in dog livers and their thrombolytic effects when combined with low-frequency ultrasound in vitro.

A new microbubble loaded with urokinase (uPA-MB) was explored in a previous study. However, its zeta potential and ultrasound contrast imaging properties and its thrombolytic effects when combined with low-frequency ultrasound (LFUS) were unclear. The zeta potential and ultrasound contrast imaging property of 5 uPA-MBs loading with 50,000 IU uPA was respectively detected using a Malvern laser particle analyzer and a Logiq 9 digital premium ultrasound system. Its ultrasound contrast imaging property was performed on the livers of two healthy dogs to compare with SonoVue. And the clot mass loss rate, D-dimer concentration and surface morphology of the clot residues were measured to evaluate the thrombolytic effect after treatment with three doses of 5 uPA-MBs combined with LFUS in vitro. The zeta potential of 5 uPA-MBs (-27.0 ± 2.40 mV) was higher than that of normal microbubbles (-36.95 ± 1.77 mV). Contrast-enhanced imaging of the hepatic vessels using 5 uPA-MBs was similar to SonoVue, while the imaging duration of 5 uPA-MBs (10 min) was longer than SonoVue (6 min). The thrombolytic effect of three doses of uPA-MBs combined with LFUS was significantly better than that of the control group and showed dose dependence. The 5 uPA-MBs have a negative charge on their surface and good echogenicity as ultrasound contrast agents. The 5 uPA-MBs combined with LFUS can promote thrombolysis in a dose-dependent manner.