Critical-sized bone defects are a difficult problem in both human and veterinary medicine. To address this issue, synthetic graft materials have been garnering attention. Abundant in vitro studies have proven the possibilities of poly(lactic-acid) (PLA) scaffolds and poly(lactide-co-glycolide)/hydroxyapatite (PLGA/HAp) nanofibres for treating bone defects. The present study aimed at conducting an in vivo assessment of the biological performance of a three dimensional (3D)-printed PLA scaffold filled with a PLGA/HAp nanofibrous scaffold to estimate its potential applications in bone defect reconstruction surgery. Defects were created in a 20 mm-long region of the radius bone. The defects created on the right side in six Beagle dogs (n = 6) were left untreated (Group 1). The defects on the left side (n = 6) were filled with 3D-printed PLA scaffolds incorporated with PLGA/Hap nanofibres with gelatine (Group 2). The other six Beagle dog defects were made bilaterally (n = 12) and filled with the same material as that used in Group 2 along with recombinant bone morphogenetic protein 2 (rhBMP-2) (Group 3). Both the radiological and histological examinations were performed for observing the reaction of the scaffold and the bone. Micro-computed tomography (CT) was utilised for the evaluation of the bone parameters 20 weeks after the experiment. The radiological and histological results revealed that the scaffold was biodegradable and was replaced by new bone tissue. The micro-CT revealed that the bone parameters were significantly (P < 0.05) increased in Group 3. Based on these results, our study serves as a foundation for future studies on bone defect treatment using synthetic polymeric scaffolds.

A perfusion-control strategy based on cellular consumption rates of oxygen and glucose was established for the production of single-chain urokinase-type plasminogen activator (scu-PA). Employing this strategy, the in¯uences of microcarrier types and the culture media on culture performances were evaluated. In the control perfusion culture, which used a solid microcarrier and a 1% fetal bovine serum (FBS) medium, viable cell density reached 3.1´10 7 cells ml A1 . However, formation of large, heterogeneous aggregates (500±1,000 lm) resulted in a gradual decrease in viable cell density to less than 1.0´10 7 cells ml A1 . Accordingly, declines in the production of urokinase-type plasminogen activator (u-PA) and in the scu-PA portion of u-PA were observed.In the serum-free media, cell growth and u-PA production were suppressed 2±3 times, but were signi®cantly enhanced when a porous microcarrier, Cultispheer G, was used. The cell-growth pro®le showed a continuous increase in cell density, reaching 5.1´10 7 cells ml A1 , and the production of u-PA remained stable throughout the culture (1586 247 IU ml A1 ). The values of all the parameters associated with cell growth and u-PA production were fairly comparable to or even higher than those in the control culture. Moreover, a 13% higher scu-PA portion of u-PA was observed in the serum-free culture, regardless of the microcarrier type, compared with scu-PA portion of u-PA in the control culture.

0 1 7 ) A 3 9 9 -A 8 1 1 A789 to PCV-13 and full reimbursement of both vaccines, the cost-saving increased to € 2,272,722 (discounted). In PSA, 95.4% simulations (n= 500) were in the dominant quadrant. ConClusions: PHiD-CV is estimated to provide both additional health benefits and cost-savings compared to PCV-13, at price parity. From the public payer perspective, a substantial budget saving is estimated using PHiD-CV compared to PCV13 in paediatric UMV in Slovakia.