Injectable mesoporous bioactive nanoparticles regenerate bone tissue under osteoporosis conditions.

The osteogenic capability of mesoporous bioactive nanoparticles (MBNPs) in the SiO2CaO system has been assessed in vivo using an osteoporotic rabbit model. MBNPs have been prepared using a double template method, resulting in spherical nanoparticles with a porous core-shell structure that has a high surface area and the ability to incorporate the anti-osteoporotic drug ipriflavone. In vitro expression of the pro-inflammatory genes NF-κB1, IL-6, TNF-α, P38 and NOS2 in RAW-264.7 macrophages, indicates that these nanoparticles do not show adverse inflammatory effects. An injectable system has been prepared by suspending MBNPs in a hyaluronic acid-based hydrogel, which has been injected intraosseously into cavitary bone defects in osteoporotic rabbits. The histological analyses evidenced that MBNPs promote bone regeneration with a moderate inflammatory response. The incorporation of ipriflavone into these nanoparticles resulted in a higher presence of osteoblasts and enhanced angiogenesis at the defect site, but without showing significant differences in terms of new bone formation. STATEMENT OF SIGNIFICANCE: Mesoporous bioactive glass nanoparticles have emerged as one of the most interesting materials in the field of bone regeneration therapies. For the first time, injectable mesoporous bioactive nanoparticles have been tested in vivo using an osteoporotic animal model. Our findings evidence that MBG nanoparticles can be loaded with an antiosteoporotic drug, ipriflavone, and incorporated in hyaluronic acid to make up an injectable hydrogel. The incorporation of MBG nanoparticles promotes bone regeneration even under osteoporotic conditions, whereas the presence of IP enhances angiogenesis as well as the presence of osteoblast cells lining in the newly formed bone. The injectable device presented in this work opens new possibilities for the intraosseous treatment of osteoporotic bone using minimally invasive surgery.

Development and assessment of an ex-vivo bench model aimed at laparoscopic ureteric reconstructive techniques.

INTRODUCTION/BACKGROUND: Reconstructive and ablative urologic techniques require special technical mastery, especially the intracorporeal suturing. OBJECTIVE: To report the subjective evaluation of a versatile ex-vivo model aimed to practice laparoscopic ureteric reconstructive techniques (LURT) on box-trainer. STUDY DESIGN: The model is a continuous portion of porcine urinary bladder ("dilated pelvis"), the vesico-ureteral joint ("stenosis") and healthy ureter. All 127 participants (n = 119 urologists and n = 8 paediatric surgeons) performed on the model laparoscopic Anderson-Hynes dismembered pyeloplasty, and then, in the animal model, different LURT procedures (ureteroneocystostomy, ureteric reimplantation and/or dismembered pyeloplasty). The model was subjectively evaluated (face and content validity), through a 12 items questionnaire, based on a Likert scale (1-5 points) and a global question (1-10 points). RESULTS: The total mean rating for 11/12 items was very high (>4points). Only one was rated under 3 points. The overall total mean rating from 1 to 10 points was very high (9.19 ± 0.82 points). In 10/12 items, expert's feedback (content validity) prevailed over non-experts (face validity). DISCUSSION/CONCLUSION: The model was highly accepted for the practice of LURT techniques. Additionally, it is cost-effective, easy to assemble, ethically considerate, and realistic.

Silicon substituted hydroxyapatite/VEGF scaffolds stimulate bone regeneration in osteoporotic sheep.

Silicon-substituted hydroxyapatite (SiHA) macroporous scaffolds have been prepared by robocasting. In order to optimize their bone regeneration properties, we have manufactured these scaffolds presenting different microstructures: nanocrystalline and crystalline. Moreover, their surfaces have been decorated with vascular endothelial growth factor (VEGF) to evaluate the potential coupling between vascularization and bone regeneration. In vitro cell culture tests evidence that nanocrystalline SiHA hinders pre-osteblast proliferation, whereas the presence of VEGF enhances the biological functions of both endothelial cells and pre-osteoblasts. The bone regeneration capability has been evaluated using an osteoporotic sheep model. In vivo observations strongly correlate with in vitro cell culture tests. Those scaffolds made of nanocrystalline SiHA were colonized by fibrous tissue, promoted inflammatory response and fostered osteoclast recruitment. These observations discard nanocystalline SiHA as a suitable material for bone regeneration purposes. On the contrary, those scaffolds made of crystalline SiHA and decorated with VEGF exhibited bone regeneration properties, with high ossification degree, thicker trabeculae and higher presence of osteoblasts and blood vessels. Considering these results, macroporous scaffolds made of SiHA and decorated with VEGF are suitable bone grafts for regeneration purposes, even in adverse pathological scenarios such as osteoporosis. STATEMENT OF SIGNIFICANCE: For the first time, the in vivo behavior of scaffolds made of silicon substituted hydroxyapatites (SiHA) has been evaluated under osteoporosis conditions. In order to optimize the bone regeneration properties of these bioceramics, 3D macroporous scaffolds have been manufactured by robocasting and implanted in osteoporotic sheep. Our experimental design shed light on the important issue of the biological response of nano-sized bioceramics vs highly crystalline bioceramics, as well as on the importance of coupling vascularization and bone growth processes by decorating SiHA scaffolds with vascular endothelial growth factor.

Synergistic effect of Si-hydroxyapatite coating and VEGF adsorption on Ti6Al4V-ELI scaffolds for bone regeneration in an osteoporotic bone environment.

The osteogenic and angiogenic responses to metal macroporous scaffolds coated with silicon substituted hydroxyapatite (SiHA) and decorated with vascular endothelial growth factor (VEGF) have been evaluated in vitro and in vivo. Ti6Al4V-ELI scaffolds were prepared by electron beam melting and subsequently coated with Ca10(PO4)5.6(SiO4)0.4(OH)1.6 following a dip coating method. In vitro studies demonstrated that SiHA stimulates the proliferation of MC3T3-E1 pre-osteoblastic cells, whereas the adsorption of VEGF stimulates the proliferation of EC2 mature endothelial cells. In vivo studies were carried out in an osteoporotic sheep model, evidencing that only the simultaneous presence of both components led to a significant increase of new tissue formation in osteoporotic bone. STATEMENT OF SIGNIFICANCE: Reconstruction of bones after severe trauma or tumors extirpation is one of the most challenging tasks in the field of orthopedic surgery. This scenario is even more complicated in the case of osteoporotic patients, since their bone regeneration capability is decreased. In this work we present a porous implant that promotes bone regeneration even in osteoporotic bone. By coating the implant with osteogenic bioceramics such as silicon substituted hydroxyapatite and subsequent adsorption of vascular endothelial growth factor, these implants stimulate the bone ingrowth when they are implanted in osteoporotic sheep.

Initial validation of a training program focused on laparoscopic radical nephrectomy. / Validación inicial de un programa de formación enfocado a la nefrectomía radical laparoscópica.

OBJECTIVE: To assess a training model focused on laparoscopic nephrectomy. MATERIAL AND METHODS: 16 residents participated in the study, who attended a training program with a theoretical session (1hour) and a dry (7hours) and a wet lab (13hours). During animal training, the first and last nephrectomies were assessed through the completion time and the global rating scale "Objective and Structured Assessment of Technical Skills" (OSATS). Before and after the course, they performed 3 tasks on the virtual reality simulator LAPMentor (1) eye-hand coordination; 2) hand-hand coordination; and 3) transference of objects), registering time and movement metrics. All participants completed a questionnaire related to the training components on a 5-point rating scale. RESULTS: The participants performed the last nephrectomy faster (P<.001) and with higher OSATS scores (P<.001). After the course, they completed the LAPMentor tasks faster (P<.05). The number of movements decreased in all tasks (1) P<.001, 2) P<.05, and 3) P<.05), and the path length in tasks 1 (P<.05) and 2 (P<.05). The movement speeds increased in tasks 2 (P<.001) and 3 (P<.001). With regards to the questionnaire, the usefulness of the animal training and the necessity of training on them prior to their laparoscopic clinical practice were the questions with the highest score (4.92±.28). CONCLUSIONS: The combination of physical simulation and animal training constitute an effective training model for improving basic and advanced skills for laparoscopic nephrectomy. The component preferred by the urology residents was the animal training.

Learning curves of basic laparoscopic psychomotor skills in SINERGIA VR simulator.

PURPOSE: Surgical simulators are currently essential within any laparoscopic training program because they provide a low-stakes, reproducible and reliable environment to acquire basic skills. The purpose of this study is to determine the training learning curve based on different metrics corresponding to five tasks included in SINERGIA laparoscopic virtual reality simulator. METHODS: Thirty medical students without surgical experience participated in the study. Five tasks of SINERGIA were included: Coordination, Navigation, Navigation and touch, Accurate grasping and Coordinated pulling. Each participant was trained in SINERGIA. This training consisted of eight sessions (R1-R8) of the five mentioned tasks and was carried out in two consecutive days with four sessions per day. A statistical analysis was made, and the results of R1, R4 and R8 were pair-wise compared with Wilcoxon signed-rank test. Significance is considered at P value <0.005. RESULTS: In total, 84.38% of the metrics provided by SINERGIA and included in this study show significant differences when comparing R1 and R8. Metrics are mostly improved in the first session of training (75.00% when R1 and R4 are compared vs. 37.50% when R4 and R8 are compared). In tasks Coordination and Navigation and touch, all metrics are improved. On the other hand, Navigation just improves 60% of the analyzed metrics. Most learning curves show an improvement with better results in the fulfillment of the different tasks. CONCLUSIONS: Learning curves of metrics that assess the basic psychomotor laparoscopic skills acquired in SINERGIA virtual reality simulator show a faster learning rate during the first part of the training. Nevertheless, eight repetitions of the tasks are not enough to acquire all psychomotor skills that can be trained in SINERGIA. Therefore, and based on these results together with previous works, SINERGIA could be used as training tool with a properly designed training program.

Validation of SINERGIA as training tool: a randomized study to test the transfer of acquired basic psychomotor skills to LapMentor.

PURPOSE: Laparoscopic surgery is commonly used in many surgical procedures but requires a learning process to develop the necessary skills. Virtual reality simulators play an essential role within the training curricula. This paper aims to determine whether training in SINERGIA VR simulator allows novice surgeons to improve their basic psychomotor laparoscopic skills. METHODS: Forty-two people participated in this study, including 28 unexperience medical students and 14 expert surgeons who developed previously more than 100 laparoscopic procedures. Medical students made a pre-training test in LapMentor II; then, they trained in SINERGIA and they finally accomplished a post-training test in LapMentor II. Experts just made one trial in LapMentor II. A statistical analysis was carried out and results of pre- and post-training tests of novices were compared with Wilcoxon signed-rank test. Pre- and post-training tests of novices were also compared with results of experts with Mann-Whitney U test. RESULTS: Most metrics provided by LapMentor II and included in this study show significant differences when comparing pre- and post-training tests of novices. Analysis of pre-training test of novices and experts results show significant differences in all analyzed metrics for all studied tasks. On the other hand, LapMentor was not able to distinguish between experts and novices after training in SINERGIA for any metric in the camera manipulation task and for some metrics of the other tasks. CONCLUSIONS: Training in SINERGIA VR simulator allows improvement of basic psychomotor laparoscpic skills and transferring them to another virtual simulator. Therefore, it could be used in laparoscopic surgery training programs.