Hybrid 3D-Printed and Electrospun Scaffolds Loaded with Dexamethasone for Soft Tissue Applications.

BACKGROUND: To make the regenerative process more effective and efficient, tissue engineering (TE) strategies have been implemented. Three-dimensional scaffolds (electrospun or 3D-printed), due to their suitable designed architecture, offer the proper location of the position of cells, as well as cell adhesion and the deposition of the extracellular matrix. Moreover, the possibility to guarantee a concomitant release of drugs can promote tissue regeneration. METHODS: A PLA/PCL copolymer was used for the manufacturing of electrospun and hybrid scaffolds (composed of a 3D-printed support coated with electrospun fibers). Dexamethasone was loaded as an anti-inflammatory drug into the electrospun fibers, and the drug release kinetics and scaffold biological behavior were evaluated. RESULTS: The encapsulation efficiency (EE%) was higher than 80%. DXM embedding into the electrospun fibers resulted in a slowed drug release rate, and a slower release was seen in the hybrid scaffolds. The fibers maintained their nanometric dimensions (less than 800 nm) even after deposition on the 3D-printed supports. Cell adhesion and proliferation was favored in the DXM-loading hybrid scaffolds. CONCLUSIONS: The hybrid scaffolds that were developed in this study can be optimized as a versatile platform for soft tissue regeneration.

Elaboration and development of a realistic 3D printed model for training in ultrasound-guided placement of peripheral central venous catheter in children.

BACKGROUND: Simulation for training is becoming a trend topic worldwide, even if its applications are commonly limited to adulthood. Ultrasound-guided procedures require practice and experience-especially in the pediatric field, where the small size of the involved anatomical structures poses major problems. In this context, a realistic 3D printed pediatric phantom for training of the ultrasound-guided placement of peripheral central venous catheters in children was developed. MATERIALS AND METHODS: Starting from Computed Tomography scans of an 8 years-old girl, her left arm was virtually reconstructed-including bones, arteries, and veins-through a semi-automatic segmentation process. According to preliminary results, the most suitable 3D printing technologies to reproduce the different anatomical structures of interest were selected, considering both direct and indirect 3D printing techniques. Experienced operators were asked to evaluate the efficacy of the final model through a dedicated questionnaire. RESULTS: Vessels produced through indirect 3D printing latex dipping technique exhibited the best echogenicity, thickness, and mechanical properties to mimic real children's venous vessels, while arteries-not treated and/or punctured during the procedure-were directly 3D printed through Material Jetting technology. An external mold-mimicking the arm skin-was 3D printed and a silicone-based mixture was poured to reproduce real patient's soft tissues. Twenty expert specialists were asked to perform the final model's validation. The phantom was rated as highly realistic in terms of morphology and functionality for the overall simulation, especially for what concerns vessels and soft tissues' response to puncturing. On the other hand, the involved structures' US appearance showed the lower score. CONCLUSIONS: The present work shows the feasibility of a patient-specific 3D printed phantom for simulation and training in pediatric ultrasound-guided procedures.

Assessment of different manufacturing techniques for the production of bioartificial scaffolds as soft organ transplant substitutes.

Introduction: The problem of organs' shortage for transplantation is widely known: different manufacturing techniques such as Solvent casting, Electrospinning and 3D Printing were considered to produce bioartificial scaffolds for tissue engineering purposes and possible transplantation substitutes. The advantages of manufacturing techniques' combination to develop hybrid scaffolds with increased performing properties was also evaluated. Methods: Scaffolds were produced using poly-L-lactide-co-caprolactone (PLA-PCL) copolymer and characterized for their morphological, biological, and mechanical features. Results: Hybrid scaffolds showed the best properties in terms of viability (>100%) and cell adhesion. Furthermore, their mechanical properties were found to be comparable with the reference values for soft tissues (range 1-10 MPa). Discussion: The created hybrid scaffolds pave the way for the future development of more complex systems capable of supporting, from a morphological, mechanical, and biological standpoint, the physiological needs of the tissues/organs to be transplanted.

Three-D-printed simulator for kidney transplantation.

BACKGROUND: Three-Dimensional (3D) printing technology can be used to manufacture training platforms for surgeons. Kidney transplantation offers a suitable model, since it mostly entails vascular and ureteric anastomoses. METHODS: A new simulation platform for surgical training in kidney transplantation was realized and validated in this study. A combination of different 3-D printing technology was used to reproduce the key anatomy of lower abdomen, of pelvis, and of a kidney graft, including their mechanical properties. RESULTS: Thirty transplantations were performed by two junior trainees with no previous experience in the area. Analysis of the times required to perform the simulated transplantation showed that proficiency was reached after about ten cases, as indicated by a flattening of the respective curves that corresponded to a shortening of about 40% and 47%, respectively, of the total time initially needed to perform the whole simulated transplantation. Although an objective assessment of the technical quality of the anastomoses failed to show a significant improvement throughout the study, a growth in self-confidence with the procedure was reported by both trainees. CONCLUSION: The quality of the presented simulation platform aimed at reproducing in the highest possible way a realistic model of the operative setting and proved effective in providing an integrated training environment where technical skills are enhanced together with a team-training experience. As a result the trainees' self-confidence with the procedure resulted enforced. Three-D--printed models can also offer pre-operative patient-specific training when anatomical variants are anticipated by medical imaging. An analysis of the costs related to the use of this platform is also provided and discussed.

An overview on 3D printing for abdominal surgery.

BACKGROUND: Three-dimensional (3D) printing is a disruptive technology that is quickly spreading to many fields, including healthcare. In this context, it allows the creation of graspable, patient-specific, anatomical models generated from medical images. The ability to hold and show a physical object speeds up and facilitates the understanding of anatomical details, eases patient counseling and contributes to the education and training of students and residents. Several medical specialties are currently exploring the potential of this technology, including general surgery. METHODS: In this review, we provide an overview on the available 3D printing technologies, together with a systematic analysis of the medical literature dedicated to its application for abdominal surgery. Our experience with the first clinical laboratory for 3D printing in Italy is also reported. RESULTS: There was a tenfold increase in the number of publications per year over the last decade. About 70% of these papers focused on kidney and liver models, produced primarily for pre-interventional planning, as well as for educational and training purposes. The most used printing technologies are material jetting and material extrusion. Seventy-three percent of publications reported on fewer than ten clinical cases. CONCLUSION: The increasing application of 3D printing in abdominal surgery reflects the dawn of a new technology, although it is still in its infancy. The potential benefit of this technology is clear, however, and it may soon lead to the development of new hospital facilities to improve surgical training, research, and patient care.

The clinical use of 3D printing in surgery.

The use of 3D printing is gaining considerable success in many medical fields including surgery. Here, the technology was introduced for increasing the level of anatomical understanding thanks to the inherent characteristics of 3D printed models: these are highly accurate and customized reproductions, being obtained from own radiological imaging of patients, and are solid graspable objects allowing for free manipulation on part of the user. The resulting tactile feedbacks significantly help the comprehension of anatomical details, especially the spatial relations between structures. In this regard, they proved to be more effective than conventional 2D imaging and 3D virtual models. To date, an increasing number of applications have been successfully tested in many surgical disciplines, extending the range of possible uses to pre-operative planning, counselling with patients, education of students and residents, surgical training, intraoperative navigation and others; in recent years, 3D printing was also employed for creating surgical tools and reproducing anatomical parts to be used, respectively, as templates or guides for specific tasks of the surgery and individualized implantable materials in reconstructive procedures. Future expectations concern on one side the reduction of manufacturing costs and time to further increase the accessibility of 3D printing, while on the other the development of novel techniques and materials suitable for 3D printing of biological structures by which recreating the architecture and functionality of real human organs and tissues.

Efficacy of CR4056, a first-in-class imidazoline-2 analgesic drug, in comparison with naproxen in two rat models of osteoarthritis.

PURPOSE: CR4056, (2-phenyl-6-(1H-imidazol-1yl) quinazoline), an imidazoline-2 (I2) receptor ligand, is a promising analgesic drug that has been reported to be effective in several animal models of pain. The aim of this study was to evaluate the effects of CR4056 in two well-established rat models of osteoarthritis (OA), mimicking the painful and structural components of human OA. METHODS: Knee OA was induced either by single intra-articular injection of monoiodoacetate (MIA) or by medial meniscal tear (MMT) in the right knee of male rats. In the MIA model, allodynia and hyperalgesia were measured as paw withdrawal threshold to mechanical stimulation. In the MMT model, pain behavior was analyzed as weight-bearing asymmetry (i.e. difference in hind paw weight distribution, HPWD) between the injured and the contralateral limbs. RESULTS: Acute oral administration of CR4056, 14 days after MIA injection, significantly and dose-dependently reduced allodynia and hyperalgesia 90 minutes after treatment, whereas acute naproxen administration significantly reduced allodynia but not hyperalgesia. After 7 days of repeated treatment, both CR4056 and naproxen showed significant anti-allodynic and anti-hyperalgesic effects in the MIA model. Rats undergoing MMT surgery developed a significant and progressive asymmetry in HPWD compared with sham-operated animals. Repeated treatment with CR4056 significantly reduced the progression of the pain behavior, whereas naproxen had no effects. CONCLUSION: The data presented here show that the I2 ligand CR4056 could be a new effective treatment for OA pain. The compound is currently under Phase II clinical evaluation for this indication.