A new liver perfusion and preservation system for transplantation Research in large animals

A kidney perfusion machine, model MOX-100 (Waters Instruments, Ltd, Rochester, MN) was modified to allow continuous perfusion of the portal vein and pulsatile perfusion of the hepatic artery of the liver. Additional apparatus consists of a cooling system, a membrane oxygenator, a filter for foreign bodies, and bubble traps. This system not only allows hypothermic perfusion preservation of the liver graft, but furthermore enables investigation of ex vivo simulation of various circulatory circumstances in which physiological perfusion of the liver is studied. We have used this system to evaluate the viability of liver allografts preserved by cold storage. The liver was placed on the perfusion system and perfused with blood with a hematocrit of approximately 20% and maintained at 37°C for 3 h. The flows of the hepatic artery and portal vein were adjusted to 0.33 mL and 0.67 mL/g of liver tissue, respectively. Parameters of viability consisted of hourly bile output, oxygen consumption, liver enzymes, electrolytes, vascular resistance, and liver histology. This method of liver assessment in large animals will allow the objective evaluation of organ viability for transplantation and thereby improve the outcome of organ transplantation. Furthermore, this pump enables investigation into the pathophysiology of liver ischemia and preservation. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted

Patient-specific 3D printed model of biliary ducts with congenital cyst

Background: 3D printing has shown great promise in medical applications, with increasing reports in liver diseases. However, research on 3D printing in biliary disease is limited with lack of studies on validation of model accuracy. In this study, we presented our experience of creating a realistic 3D printed model of biliary ducts with congenital cyst. Measurements of anatomical landmarks were compared at different stages of model generation to determine dimensional accuracy. Methods: Contrast-enhanced computed tomography (CT) images of a patient diagnosed with congenital cyst in the common bile duct with dilated hepatic ducts were used to create the 3D printed model. The 3D printed model was scanned on a 64-slice CT scanner using the similar abdominal CT protocol. Measurements of anatomical structures including common hepatic duct (CHD), right hepatic duct (RHD), left hepatic duct (LHD) and the cyst at left to right and anterior to posterior dimensions were performed and compared between original CT images, the standard tessellation language (STL) image and CT images of the 3D model. Results: The 3D printing model was successfully generated with replication of biliary ducts and cyst. Significant differences in measurements of these landmarks were found between the STL and the original CT images, and the CT images of the 3D printed model and the original CT images (

3D printing in medicine: current applications and future directions

Technical developments in medical imaging techniques have led to significant improvements in the diagnostic performance of less-invasive imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), nuclear medicine and ultrasound. Quantitative analysis of these imaging modalities allows for detection and diagnosis of various diseases with high accuracy (1-10). Despite promising results available in the literature, traditional two-dimensional (2D) and three-dimensional (3D) visualization tools are still limited to a 2D screen, which affect realistic visualization of anatomical structures and pathologies of 3D datasets, and this is particularly apparent when dealing with complex pathologies. This has created potential opportunities for the use of 3D printing technique in medical applications

RVS for small lesion in hepatectomy

Background : Systemic chemotherapy can drastically downsize metastatic liver tumors and these small liver lesions could sometimes be difficult for surgeons to detect during hepatectomy. We assessed the usefulness of intraoperative real-time virtual sonography (RVS) with contrast-enhanced ultrasonography (CEUS) using ‘Sonazoid’ contrast agent (RVS-CEUS). Methods : We performed the intraoperative RVS-CEUS technique on 10 tumor lesions in six cases, which were scheduled for hepatic resection of < 10 mm in diameter in our liver metastases series. These lesions were preoperatively diagnosed by contrast enhanced-computed tomography (CE-CT) or Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (EOB-MRI). We assessed the detectability of a tumor with RVS-CEUS during surgery and compared it with that of preoperative CE-CT or EOB-MRI. Results : Detectability of RVS-CEUS for 10 small lesions was 90% (n = 9/10) and that of other preoperative modalities were 50% (n = 5/10, CE-CT) and 100% (n = 10/10, EOB-MRI). Minimum tumor size detected was 3.0 mm in diameter, and maximum depth of detection with RVS-CEUS was 43.5 mm ; these results could be an advantage when compared with other intraoperative diagnostic modalities. Conclusion : Intraoperative RVS-CEUS was useful for detecting small metastatic liver lesions after chemotherapy and could be an effective intraoperative diagnostic technique for hepatic resection of a size < 10 mm

Recent advances in 3D printing of biomaterials.

3D Printing promises to produce complex biomedical devices according to computer design using patient-specific anatomical data. Since its initial use as pre-surgical visualization models and tooling molds, 3D Printing has slowly evolved to create one-of-a-kind devices, implants, scaffolds for tissue engineering, diagnostic platforms, and drug delivery systems. Fueled by the recent explosion in public interest and access to affordable printers, there is renewed interest to combine stem cells with custom 3D scaffolds for personalized regenerative medicine. Before 3D Printing can be used routinely for the regeneration of complex tissues (e.g. bone, cartilage, muscles, vessels, nerves in the craniomaxillofacial complex), and complex organs with intricate 3D microarchitecture (e.g. liver, lymphoid organs), several technological limitations must be addressed. In this review, the major materials and technology advances within the last five years for each of the common 3D Printing technologies (Three Dimensional Printing, Fused Deposition Modeling, Selective Laser Sintering, Stereolithography, and 3D Plotting/Direct-Write/Bioprinting) are described. Examples are highlighted to illustrate progress of each technology in tissue engineering, and key limitations are identified to motivate future research and advance this fascinating field of advanced manufacturing

Three-Dimensional Printed Liver Models for Surgical Planning and Intraoperative Guidance of Liver Cancer Resection: A Systematic Review

Successful liver cancer resection requires a comprehensive pre- and intraoperative understanding of the spatial relationships between a patient’s cancer and intrahepatic anatomy. The recent literature has highlighted that patient-specific 3D-printed liver models (3DPLMs) reconstructed from medical imaging data may enhance the comprehension of patients’ liver anatomy and thereby provide a useful preoperative planning and intraoperative guidance tool for liver cancer resection (LCR). The purpose of this systematic review was to critically examine the utility and feasibility of 3DPLMs for LCR surgical planning and intraoperative guidance and explore whether these applications improve patient outcomes. Articles were retrieved from four electronic databases (Scopus, Embase, PubMed, and Curtin University Database) according to predetermined eligibility criteria. In total, 22 eligible articles were identified, including 11 original research articles and 11 case reports. Key concepts were synthesised using an inductive content analysis approach suitable for this heterogeneous body of literature. There is significant descriptive and case-report evidence that 3DPLMs strengthen pre- and intraoperative comprehension of patient liver and liver tumour anatomy and can enhance pre- and intraoperative surgical decision making for LCR. The analysis of these studies presents large variances in the times and costs necessary to produce 3DPLMs, as studies did not provide the full expenses of materials, software, and equipment. Production times were focused on different aspects of the 3D printing process and were not comparable. The review nonetheless demonstrates the potential value of 3DPLMs as preoperative planning and intraoperative guidance tools for LCR. Future studies should detail these economic data points to ensure 3DPLMs’ viability. Further experimental research and randomised controlled trials are also necessary to examine the relationship between 3DPLMs and patient’s intra- and postoperative outcomes

Printing three-dimensional tissue analogues with decellularized extracellular matrix bioink

The ability to print and pattern all the components that make up a tissue (cells and matrix materials) in three dimensions to generate structures similar to tissues is an exciting prospect of bioprinting. However, the majority of the matrix materials used so far for bioprinting cannot represent the complexity of natural extracellular matrix (ECM) and thus are unable to reconstitute the intrinsic cellular morphologies and functions. Here, we develop a method for the bioprinting of cell-laden constructs with novel decellularized extracellular matrix (dECM) bioink capable of providing an optimized microenvironment conducive to the growth of three-dimensional structured tissue. We show the versatility and flexibility of the developed bioprinting process using tissue-specific dECM bioinks, including adipose, cartilage and heart tissues, capable of providing crucial cues for cells engraftment, survival and long-term function. We achieve high cell viability and functionality of the printed dECM structures using our bioprinting method.open11349353sciescopu

Characterization of susceptibility artifacts in magnetic resonance thermometry images during laser interstitial thermal therapy: dimension analysis and temperature error estimation

Objective: Laser interstitial thermal therapy (LITT) is a minimally invasive procedure used to treat a lesion through light irradiation and consequent temperature increase. Magnetic Resonance Thermometry Imaging (MRTI) provides a multidimensional measurement of the temperature inside the target thus enabling accurate monitoring of the zone of damage during the procedure. In proton resonance frequency shift-based thermometry, artifacts in the images may strongly interfere with the estimated temperature maps. In our work, after noticing the formation of the dipolar-behavior artifact linkable to magnetic susceptibility changes during in vivo LITT, an investigation of susceptibility artifacts in tissue-mimicking phantoms was implemented. Approach: The artifact was characterized: (i) by measuring the area and total volume of error regions and their evolution during the treatment; and (ii) by comparison with temperature reference provided by three temperature sensing needles. Lastly, a strategy to avoid artifacts formation was devised by using the temperature-sensing needles to implement a temperature-controlled LITT. Main results: The artifact appearance was associated with gas bubble formation and with unwanted treatment effects producing magnetic susceptibility changes when 2 W laser power was set. The analysis of the artifact's dimension demonstrated that in the sagittal plane the dipolar-shape artifact may consistently spread following the temperature trend until reaching a volume 8 times bigger than the ablated one. Also, the artifact shape is quite symmetric with respect to the laser tip. An absolute temperature error showing a negative Gaussian profile in the area of susceptibility artifact with values up to 64.4 °C was estimated. Conversely, a maximum error of 2.8 °C is measured in the area not-affected by artifacts and far from the applicator tip. Finally, by regulating laser power, susceptibility artifacts formation was avoided, and appreciable thermal damage was induced. Significance: Such findings may help in improving the MRTI-based guidance of thermal therapies

The development of a soft tissue mimicking hydrogel: Mechanical characterisation and 3D printing

Accurate tissue phantoms are difficult to design due to the complex hyperelastic, viscoelastic and biphasic properties of real soft tissues. The aim of this work is to demonstrate the tissue mimicking ability of a composite hydrogel (CH), constituting of poly(vinyl alcohol) (PVA) and phytagel (PHY), as a soft tissue phantom over a range mechanical properties, for a variety of biomedical and tissue engineering applications. Its compressive stress-strain behaviour, relaxation response, tensile impact stresses and surgical needle-tissue interactions were mapped and characterised with respect to its constituent hydrogel formulation. The mechanical characterisation of biological tissues was also investigated and the results were used as the ground truth for mimicking. The best mimicking hydrogel compositions were determined by combining the most relevant mechanical properties for each desired application. This thesis demonstrates the use of the tissue mimicking composite hydrogel formulations as tissue phantoms for various surgical procedures, including convection enhanced drug delivery, and traumatic brain injury studies. To expand the applications of the CH, a preliminary biological evaluation of the hydrogel was performed using human dermal fibroblasts. Cell seeded on the collagen-coated composite hydrogel showed good attachment and viability. Finally, a novel fabrication method with the aim of creating samples that replicate the anisotropic properties of biological tissues was developed. A cryogenic 3D printing method utilising the liquid to solid phase change of the composite hydrogel ink was achieved by rapidly cooling the ink solution below its freezing point. The setup was able to successfully create complex 3D brain mimicking material. The method was validated by showing that the mechanical and microstructural properties of the 3D printed material was well matched to its cast-moulded equivalent. This greatly widens the applications of the CH as a mechanically accurate tool for in-vitro testing and also demonstrates promise for future mechanobiology and tissue engineering studies.Open Acces