Comparison of hand and semiautomatic tracing methods for creating maxillofacial artificial organs using sequences of computed tomography (CT) and cone beam computed tomography (CBCT) images.

INTRODUCTION: The aim of this study was to compare the paranasal sinus volumes obtained by manual and semiautomatic imaging software programs using both CT and CBCT imaging. METHODS: 121 computed tomography (CT) and 119 cone beam computed tomography (CBCT) examinations were selected from the databases of the authors' institutes. The Digital Imaging and Communications in Medicine (DICOM) images were imported into 3-dimensonal imaging software, in which hand mode and semiautomatic tracing methods were used to measure the volumes of both maxillary sinuses and the sphenoid sinus. The determined volumetric means were compared to previously published averages. RESULTS: Isometric CBCT-based volume determination results were closer to the real volume conditions, whereas the non-isometric CT-based volume measurements defined coherently lower volumes. By comparing the 2 volume measurement modes, the values gained from hand mode were closer to the literature data. Furthermore, CBCT-based image measurement results corresponded to the known averages. CONCLUSIONS: Our results suggest that CBCT images provide reliable volumetric information that can be depended on for artificial organ construction, and which may aid the guidance of the operator prior to or during the intervention.

Artificial organs 2014: a year in review.

In this Editor's Review, articles published in 2014 are organized by category and briefly summarized. We aim to provide a brief reflection of the currently available worldwide knowledge that is intended to advance and better human life while providing insight for continued application of technologies and methods of organ Replacement, Recovery, and Regeneration. As the official journal of the International Federation for Artificial Organs, the International Faculty for Artificial Organs, the International Society for Rotary Blood Pumps, the International Society for Pediatric Mechanical Cardiopulmonary Support, and the Vienna International Workshop on Functional Electrical Stimulation, Artificial Organs continues in the original mission of its founders "to foster communications in the field of artificial organs on an international level." Artificial Organs continues to publish developments and clinical applications of artificial organ technologies in this broad and expanding field of organ Replacement, Recovery, and Regeneration from all over the world. We take this time also to express our gratitude to our authors for offering their work to this journal. We offer our very special thanks to our reviewers who give so generously of time and expertise to review, critique, and especially provide meaningful suggestions to the author's work whether eventually accepted or rejected. Without these excellent and dedicated reviewers, the quality expected from such a journal could not be possible. We also express our special thanks to our Publisher, John Wiley & Sons, for their expert attention and support in the production and marketing of Artificial Organs. We look forward to reporting further advances in the coming years.

Acoustic method for calibration of audiometric bone vibrators.

The standard method for the calibration of audiometric bone vibrators requires the use of an artificial mastoid, a device that converts vibratory energy to an electrical analog. The mechanical input impedance of the device is designed to represent the average mechanical impedance of the human head. For calibration purposes, it is not necessary that the coupling device represent the impedance of the head. It is only necessary that it provides a repeatable measurement of the output of the vibrator that can be related to the normal threshold of hearing at each test frequency. In addition to the mechanical output that serves as the stimulus for the hearing test, bone vibrators produce an acoustic signal that is proportional to the mechanical force delivered to the head. By determining the transfer function relating the acoustic sound pressure to the mechanical force, the acoustic signal can serve as a proxy for the vibratory stimulus. This article describes the design and validation of an acoustic coupler for the calibration of audiometric bone vibrators.

Extended healing validation of an artificial tendon to connect the quadriceps muscle to the Tibia: 180-day study.

Whenever a tendon or its bone insertion is disrupted or removed, existing surgical techniques provide a temporary connection or scaffolding to promote healing, but the interface of living to non-living materials soon breaks down under the stress of these applications, if it must bear the load more than acutely. Patients are thus disabled whose prostheses, defect size, or mere anatomy limit the availability or outcomes of such treatments. Our group developed the OrthoCoupler™ device to join skeletal muscle to prosthetic or natural structures without this interface breakdown. In this study, the goat knee extensor mechanism (quadriceps tendon, patella, and patellar tendon) was removed from the right hind limb in 16 goats. The device connected the quadriceps muscle to a stainless steel bone plate on the tibia. Mechanical testing and histology specimens were collected from each operated leg and contralateral unoperated control legs at 180 days. Maximum forces in the operated leg (vs. unoperated) were 1,400 ± 93 N (vs. 1,179 ± 61 N), linear stiffnesses were 33 ± 3 N/mm (vs. 37 ± 4 N/mm), and elongations at failure were 92.1 ± 5.3 mm (vs. 68.4 ± 3.8 mm; mean ± SEM). Higher maximum forces (p = 0.02) and elongations at failure (p=0.008) of legs with the device versus unoperated controls were significant; linear stiffnesses were not (p=0.3). We believe this technology will yield improved procedures for clinical challenges in orthopedic oncology, revision arthroplasty, tendon transfer, and tendon injury reconstruction.

The Boston Type I keratoprosthesis: an assessment of its efficacy and safety.

BACKGROUND AND OBJECTIVE: To evaluate the efficacy and safety of the Boston Type I keratoprosthesis. PATIENTS AND METHODS: Twelve patients who underwent surgery with implantation of the Boston Type I keratoprosthesis were monitored. The following parameters were considered: diagnosis, comorbidity, previous surgery, preoperative and postoperative visual acuity, complications, and keratoprosthetic retention. RESULTS: The follow-up period ranged from 6 to 42 months (mean: 23 months). The mean number of previous keratoplasties was 2.0. The percentage of patients whose best-corrected visual acuity improved was 83.3%, and 16.7% maintained their previous vision. No patient had preoperative visual acuity better than 0.05. Patients with glaucoma comorbidity had the most limited final postoperative vision. Four eyes presented limited corneal melt. In another two eyes, corneal stromal bleeding led to a vitreous hemorrhage that was completely resolved after some weeks. No endophthalmitis or extrusion of the device occurred. CONCLUSION: The Boston Type I keratoprosthesis has a visual rehabilitation potential in cases of complicated corneal blindness, where the prognosis of a conventional keratoplasty is considered poor. Anatomical retention may be favorable in the medium term.

Innervation of tissue-engineered recombinant human collagen-based corneal substitutes: a comparative in vivo confocal microscopy study.

PURPOSE: To compare reinnervation in recombinant human collagen-based corneal substitutes with allografts during a 1-year postimplantation follow-up period in pigs. A retrospective comparison to innervation in porcine collagen-based biosynthetic grafts was also performed. METHODS: Pigs received a corneal allograft or a substitute made of either recombinant human type-I or -III collagen. In vivo confocal microscopic examination of the central cornea of surgical and untouched control eyes before surgery and at 2, 6, and 12 months after surgery was performed to quantify the number, density, and diameter of nerves at various corneal depths. RESULTS: By 12 months after surgery, the number and density of regenerated nerves in the anterior and deep anterior corneal stroma recovered to preoperative and control levels in both types of substitute grafts and in the allografts. In the subepithelial and subbasal regions, however, significantly fewer nerves were detected relative to those in control subjects at 12 months, regardless of graft type (P < 0.05), similar to the behavior of porcine collagen-based biosynthetic grafts. An absence of thick stromal nerve trunks (diameter, >10 mum) in all grafts, irrespective of material type, indicated that nerve regeneration in grafts was accompanied by persistent morphologic changes. CONCLUSIONS: Nerve regeneration in recombinant human collagen-based biosynthetic corneal grafts proceeded similarly to that in allograft tissue, demonstrating the suitability of recombinant human collagen constructs as nerve-friendly corneal substitutes. Furthermore, only minor differences were noted between type-I and -III collagen grafts, indicating an insensitivity of nerve regeneration to initial collagen type.

Towards improved artificial lungs through biocatalysis.

Inefficient CO(2) removal due to limited diffusion represents a significant barrier in the development of artificial lungs and respiratory assist devices, which use hollow fiber membranes (HFMs) as the blood-gas interface and can require large blood-contacting membrane area. To offset the underlying diffusional challenge, "bioactive" HFMs that facilitate CO(2) diffusion were prepared via covalent immobilization of carbonic anhydrase (CA), an enzyme which catalyzes the conversion of bicarbonate in blood to CO(2), onto the surface of plasma-modified conventional HFMs. This study examines the impact of enzyme attachment on the diffusional properties and the rate of CO(2) removal of the bioactive membranes. Plasma deposition of surface reactive hydroxyls, to which CA could be attached, did not change gas permeance of the HFMs or generate membrane defects, as determined by scanning electron microscopy, when low plasma discharge power and short exposure times were employed. Cyanogen bromide activation of the surface hydroxyls and subsequent modification with CA resulted in near monolayer enzyme coverage (88%) on the membrane. The effect of increased plasma discharge power and exposure time on enzyme loading was negligible while gas permeance studies showed enzyme attachment did not impede CO(2) or O(2) diffusion. Furthermore, when employed in a model respiratory assist device, the bioactive membranes improved CO(2) removal rates by as much as 75% from physiological bicarbonate solutions with no enzyme leaching. These results demonstrate the potential of bioactive HFMs with immobilized CA to enhance CO(2) exchange in respiratory devices.

The role of connexins in the differentiation of NT2 cells in Sertoli-NT2 cell tissue constructs grown in the rotating wall bioreactor.

Neural transplantation is developing as a successful treatment for neurodegenerative diseases such as Parkinson's disease. The human Ntera-2/D1 (NT2) cell line is an attractive alternative to the use of human fetal neurons as a cell source for transplantation. We have explored combining NT2 cells, as a neuronal source, and Sertoli cells, which may act as a graft facilitator to enhance neuronal survival and differentiation, and ameliorate the host immune response, into a tissue construct for use in cell replacement therapy for neurodegenerative disease. This Sertoli-NT2-aggregated cell (SNAC) tissue construct is formed in the high aspect ratio vessel (HARV) bioreactor. NT2 cells differentiate to dopaminergic NT2N neurons within the SNAC tissue construct without retinoic acid. We report here that the gap junction protein connexin 43 is decreased among differentiated NT2N neurons. Inhibition of connexin 43 with 18beta glycyrrhetinic acid and carbenoxolone, a glycyrrhetinic acid derivative, during formation of the SNAC tissue constructs disrupts the differentiation of NT2 cells. Therefore, connexin 43 is important in the differentiation of NT2 cells in the SNAC tissue construct.

Functional evaluation of an artificial anal sphincter using shape memory alloys.

This article describes an implantable artificial anal sphincter using shape memory alloys and its in vivo assessment in porcine models. The new design was developed as a low invasive prosthesis with a simple structure to solve the problem of severe fecal incontinence in patients with hypoplastic sphincters or without anal sphincters and especially for ostomates. The artificial anal sphincter consists of two shape memory alloy (SMA) plates as the main functional parts to perform two basic functions when the SMA artificial sphincter is fitted around intestines (i.e., an occlusion at body temperature and an opening function on heating). Our previous assessments with short-term animal experiments revealed promising properties with the occlusion function of the device, although some complications, such as overpressure induced ischemia, heat burn, and infections, remained. This article addresses the concerns related to the practical use of the device, the power supplement to drive the actuator, and overheating protection of the device inside bodies. Results of chronic animal experiments of up to 4 weeks suggested great potential for the improved device.

Systematic review of safety and effectiveness of an artificial bowel sphincter for faecal incontinence.

BACKGROUND: The aim was to determine the safety and effectiveness of the implantation of an artificial bowel sphincter for the treatment of severe faecal incontinence. METHOD: Medical bibliographic databases, the internet and reference lists were searched from January 1966 to January 2003. Only the lowest level of evidence was available for inclusion in this systematic review. Case series and case reports were selected to assess safety, whereas only case series were selected to assess effectiveness. RESULTS: Fourteen studies met the inclusion criteria. A number of safety issues were reported, including high explantation rates, and rates of adverse events owing to infection, device malfunction, ulceration and pain. Results in published reports were not analysed on an intention-to-treat basis. Continence, quality of life and manometry scores were reported for patients with a functioning device at the end of follow-up. These patients experienced a significant improvement in their level of continence. As no outcome data were presented for those with a non-functioning or explanted device, it is possible that such patients may have a worsened degree of incontinence or decreased quality of life. CONCLUSION: Implantation of an artificial bowel sphincter is of uncertain benefit and may possibly harm many patients. Patient selection is therefore critical and should be enhanced by higher-quality research.

Progress on regulations for human-derived therapeutic products.

Several European work programmes are building a unified regulatory framework for therapeutic products that utilise material of human origin, that is, substances, derivatives or tissues of human origin or viable cells of human origin. This is a report on progress to date.

Cell and organ printing 2: fusion of cell aggregates in three-dimensional gels.

We recently developed a cell printer (Wilson and Boland, 2003) that enables us to place cells in positions that mimic their respective positions in organs. However, this technology was limited to the printing of two-dimensional (2D) tissue constructs. Here we describe the use of thermosensitive gels to generate sequential layers for cell printing. The ability to drop cells on previously printed successive layers provides a real opportunity for the realization of three-dimensional (3D) organ printing. Organ printing will allow us to print complex 3D organs with computer-controlled, exact placing of different cell types, by a process that can be completed in several minutes. To demonstrate the feasibility of this novel technology, we showed that cell aggregates can be placed in the sequential layers of 3D gels close enough for fusion to occur. We estimated the optimum minimal thickness of the gel that can be reproducibly generated by dropping the liquid at room temperature onto a heated substrate. Then we generated cell aggregates with the corresponding (to the minimal thickness of the gel) size to ensure a direct contact between printed cell aggregates during sequential printing cycles. Finally, we demonstrated that these closely-placed cell aggregates could fuse in two types of thermosensitive 3D gels. Taken together, these data strongly support the feasibility of the proposed novel organ-printing technology.

Multicentre retrospective analysis of the outcome of artificial anal sphincter implantation for severe faecal incontinence.

BACKGROUND: A new prosthetic device, the Action artificial anal sphincter, has recently been introduced for treating severe faecal incontinence. The results of this procedure in 28 patients are presented. METHODS: The patients underwent operation for severe faecal incontinence in four Italian university hospitals and patients were reviewed after a median follow-up of 19 (range 7-41) months. RESULTS: Early infections occurred in four patients, requiring removal of the device in three. Dehiscence of the perineal wound occurred in nine patients. After activation of the device, the cuff had to be removed in a further four patients (for rectal erosion in two, anal pain in one and late infection in one). The cuff was accidentally broken in one patient. A new anal cuff was repositioned successfully in two patients. Overall, five patients had complete removal of the device and two removal of the cuff only. Twenty-one patients available for long-term evaluation had a major improvement in faecal continence. Median resting anal pressure increased from 27 mmHg before surgery to 32 mmHg after operation. Preoperative squeeze pressure was 42 mmHg while maximum postoperative anal pressure with the activated device was 67 mmHg. The median American Medical System incontinence score decreased significantly from 98.5 to 5.5 (P < 0.001). Similar figures were observed using the Continence Grading Scale (from 14.9 to 2.6; P < 0.001). Twelve patients developed symptoms of obstructed defaecation while two patients complained of anal pain. CONCLUSION: Improved continence was achieved after neosphincter implantation in three-quarters of the patients. Early infection and rectal erosion, together with difficulty in evacuating, are still major concerns with this technique.

Artificial organs and vanishing boundaries.

With the first clinical use of the artificial kidney over 5 decades ago, we entered into a new era of medicine-that of substitutive and replacement therapy. Yet it took nearly another 15 years until chronic treatment was possible and nearly another 15 years until widespread treatment was possible due to government support. The history of development and clinical use of other artificial organ technologies such as the artificial heart and heart valves, the artificial lung, artificial blood, joint replacements, the artificial liver, the artificial pancreas, immunologic, metabolic, and neurologic support, neurocontrol, and tissue substitutes have followed similar long development paths. Despite their relatively long time to be put into clinical use, the contributions of artificial organ technologies to the betterment of mankind have been unquestionably a major success. For example, modern day surgery would not be possible without heart-lung support, and the technologies for heart support have led to the development of various minimally invasive technologies. The powerful impact that artificial organ technologies presently has on our lives is seen through the statistic that in the U.S.A. nearly 1 in 10 persons is living with an implanted medical device. With the aging of our population and the improvements in technologies, these numbers will only increase.