Comparison of macroscopic resorption time for a self-locking device and suture material in ovarian pedicle ligation in dogs.

A resorbable self-locking device (LigaTie) was developed to enable safe and easy surgical ligation of blood vessels. The aim of this study was to compare the long-term in vivo resorption of the device to a commercially available suture of equivalent material (Maxon) following ovarian pedicle ligation. After ovariohysterectomy follow-up ultrasound examinations were performed monthly on 21 dogs ligated with the device and 22 dogs ligated with the suture material until no hyperechoic remnants, acoustic shadowing or local tissue reactions were detected. In both groups, the ovarian pedicles gradually decreased in size. Ligation material was considered macroscopically resorbed when ultrasound showed no signs of the device or suture, ovarian pedicle or tissue reaction. Macroscopic resorption had occurred without signs of complications and was complete by four months for sutures and 5.5 months for the device. The results show that resorption time in vivo for the resorbable self-locking device is mildly longer than suture of the same material and that no complications of device resorption were detected, supporting that the resorbable self-locking device is safe for in vivo use.

Resorbable Self-Locking Implant for Lung Lobectomy Through Video-Assisted Thoracoscopic Surgery: First Live Animal Application.

The aim of this pilot test was to test a new self-locking resorbable implant for hilum occlusion during a video-assisted thoracoscopic lung lobectomy in a surviving pig model. Once the thoracic cavity was assessed and structures identified, the right middle lobe and its respective hilum were exposed. The implant was introduced with a semiclosed loop through a working channel and positioned around the pulmonary lobe. Occlusion was performed with a conventional Crile forceps and a laparoscopic Kelly forceps. Lobe section was done with laparoscopic Metzenbaum scissors and tissue removal through the dorsal access. No signs of pneumothorax or bleeding were observed during a 60-day follow-up. Necropsy findings showed minimal pleuritis in caudal access and in the lobar stump. A granulomatous formation was found around a dense, amorphous material, which was identified as remains of a small part of the implant. Histopathological findings showed signs of a chronic healing process without other alterations. The resorbable implant LigaTie appears to exhibit similar handling and application characteristics during surgery as nonsurgical tie wraps. The resorbable implant avoids the uncontrolled substances not suitable for implants of conventional ties. The results of this pilot test suggested the resorbable implant's mechanical properties provided effective tissue support to complete the healing of the pulmonary hilum.

Ligation of the mesovarium in dogs with a self-locking implant of a resorbable polyglycolic based co-polymer: a study of feasibility and comparison to suture ligation.

BACKGROUND: Ligation of the mesovarium in female dogs may be cumbersome with risk of complications and is associated with intense noxious stimuli. A resorbable implant, a self-locking loop designed for surgery, was developed as an alternative to traditional ligation. The study aimed to test the feasibility of ligating the canine ovarian pedicle with the implant and to compare its performance to traditional suture ligation. RESULTS: In total 45 intact female dogs destined for elective ovariohysterectomy and adoption were included. In 21 dogs the new resorbable implant was used to ligate the mesovarium, and in 24 control dogs traditional suture was used with one encircling ligature. Mean weight of implant dogs was 10.7 ± 5.6 kg (range 3.5-22.0), and mean weight of control dogs was 12.8 ± 6.4 kg, (range 4.1-27.0). The body weight of dogs did not differ between groups (P = 0.25). In total, 42 ovarian pedicles were successfully ligated with the implant. In one control dog, intraoperative haemorrhage from the left ovarian pedicle was diagnosed. The mesovarium was re-ligated and haemostasis was confirmed. All dogs recovered uneventfully. The ligation time of the mesovarium was significantly shortened (P = 0.02) by using the self-locking implant versus a single ligature (3'28'' ± 1'05'' and 5'29'' ± 3'54'', respectively). Total duration of surgery differed between the groups (P = 0.02) with a shortened duration of surgery when using the self-locking implant (15'56'' ± 2'47'' and 20'39'' ± 8'58'', study group versus control group, respectively). In both groups, duration of surgery and time required to ligate the ovarian pedicle were longer in larger dogs than smaller dogs. CONCLUSION: The results of this feasibility study suggested the implant can be used to ligate the canine mesovarium. Compared with traditional suture ligation, the results suggested that time to ligate the ovarian pedicle and duration of surgery were significantly reduced with the implant. More time was required to perform surgeries in larger dogs.

Ligation of the spermatic cord in dogs with a self-locking device of a resorbable polyglycolic based co-polymer--feasibility and long-term follow-up study.

BACKGROUND: New surgical techniques are developed to enable a quicker, easier and safer surgery with reduced risk of complications and shortened time needed for recovery. A resorbable device, a self-locking loop, was designed for surgical ligation. The objective of this pilot study was to investigate the feasibility of ligating the spermatic cord with the device, its biocompatibility and long-term resorption in dogs. RESULTS: The device was made of a block co-polymer (glycolide and trimethylene carbonate), manufactured by injection moulding and consisted of a flexible band running through a case with a locking mechanism. Ten devices were tested for ligation of the spermatic cords in five dogs admitted for routine neutering. The dogs were monitored by physical examination and ultrasonography of the site of ligation, area of spermatic cord and medial iliac lymph nodes regularly until no hyperechoic remnants of the device or acoustic shadowing or local tissue reactions were observed. Haemostasis of the spermatic cords was achieved with the devices. On ultrasonography the devices were seen as hyperechoic structures for 2 months after neutering causing acoustic shadowing for 1 month. The dogs were monitored for 3 - 5 months after surgery. Gradual decrease in echogenicity and final disappearance of the hyperechoic structures suggested resorption. Macroscopic and histological post mortem examinations were performed in one dog at 3 months after surgery. Post mortem examination showed a tissue reaction of a suture granuloma that was restricted in extent at site of the device. CONCLUSIONS: The results of this pilot study suggest biocompatibility and indicate that ligation of the spermatic cord is feasible with the device.

Modeling and robust pooling design of a preparative cation-exchange chromatography step for purification of monoclonal antibody monomer from aggregates.

This study has implemented and calibrated a model that describes the separation of the monomer of monoclonal antibodies from the dimer and larger oligomers on preparative-scale using cation-exchange chromatography. A general rate model with temperature dependent diffusion was coupled to a pH- and temperature-dependent steric mass action model. The model was shown to predict the retention of the monomer, dimer, and oligomer at low loadings for different pH levels and temperatures. Additionally, the model was shown to adequately predict the elution behavior of the monomer and soluble aggregates at high loadings within the same ranges with some limitations. The model was not able to accurately describe the shape of the product break-through curves or the slight levels of co-elution of the dimer and oligomer with the monomer at higher pH. The model was used to predict how 12 process variations impact the separation. The model is used to establish an elution end collection criterion such that the step can robustly provide the target purity of monomers.

Experimental productivity rate optimization of rare earth element separation through preparative solid phase extraction chromatography.

Separating individual rare earth elements from a complex mixture with several elements is difficult and this is emphasized for the middle elements: Samarium, Europium and Gadolinium. In this study we have accomplished an overloaded one-step separation of these rare earth elements through preparative ion-exchange high-performance liquid chromatography with an bis (2-ethylhexyl) phosphoric acid impregnated column and nitric acid as eluent. An inductively coupled plasma mass spectrometry unit was used for post column element detection. The main focus was to optimize the productivity rate, subject to a yield requirement of 80% and a purity requirement of 99% for each element, by varying the flow rate and batch load size. The optimal productivity rate in this study was 1.32kgSamarium/(hmcolumn(3)), 0.38kgEuropium/(hmcolumn(3)) and 0.81kgGadolinium/(hmcolumn(3)).

Kinetic modeling of lipase-catalyzed esterification reaction between oleic acid and trimethylolpropane: a simplified model for multi-substrate multi-product ping-pong mechanisms.

Kinetic models are among the tools that can be used for optimization of biocatalytic reactions as well as for facilitating process design and upscaling in order to improve productivity and economy of these processes. Mechanism pathways for multi-substrate multi-product enzyme-catalyzed reactions can become very complex and lead to kinetic models comprising several tens of terms. Hence the models comprise too many parameters, which are in general highly correlated and their estimations are often prone to huge errors. In this study, Novozym(®) 435 catalyzed esterification reaction between oleic acid (OA) and trimethylolpropane (TMP) with continuous removal of side-product (water) was carried out as an example for reactions that follow multi-substrate multi-product ping-pong mechanisms. A kinetic model was developed based on a simplified ping-pong mechanism proposed for the reaction. The model considered both enzymatic and spontaneous reactions involved and also the effect of product removal during the reaction. The kinetic model parameters were estimated using nonlinear curve fitting through unconstrained optimization methodology and the model was verified by using empirical data from different experiments and showed good predictability of the reaction under different conditions. This approach can be applied to similar biocatalytic processes to facilitate their optimization and design.

Degradation profile and preliminary clinical testing of a resorbable device for ligation of blood vessels.

A resorbable device for ligation of blood vessels was developed and tested in vitro to reveal the degradation profile of the device and to predict the clinical performance in terms of adequate mechanical support during a healing period of 1week. In addition, preliminary clinical testing was performed that showed complete hemostasis and good tissue grip of renal arteries in five pigs. The device was made by injection molding of poly(glycolide-co-trimethylene carbonate) triblock copolymer, and it consisted of a case with a locking mechanism connected to a partly perforated flexible band. A hydrolytic degradation study was carried out for 7, 30 and 60days in water and buffer medium, following the changes in mass, water absorption, pH and mechanical properties. A new rapid matrix-free laser desorption ionization-mass spectrometry (LDI-MS) method was developed for direct screening of degradation products released into the degradation medium. The combination of LDI-MS and electrospray ionization-mass spectrometry analyses enabled the comparison of the degradation product patterns in water and buffer medium. The identified degradation products were rich in trimethylene carbonate units, indicating preferential hydrolysis of amorphous regions where trimethylene units are located. The crystallinity of the material was doubled after 60days of hydrolysis, additionally confirming the preferential hydrolysis of trimethylene carbonate units and the enrichment of glycolide units in the remaining solid matrix. The mechanical performance of the perforated band was followed for the first week of hydrolysis and the results suggest that sufficient strength is retained during the healing time of the blood vessels.

Modelling and optimisation of preparative chromatographic purification of europium.

A model commonly used to describe the separation of biomolecules was used to simulate the harsh environment when eluting neodymium, samarium, europium and gadolinium with a hot acid. After calibration, the model was used to optimise the preparative separation of europium, as this is the most valuable of the four elements. A kinetic dispersive model with a Langmuir mobile phase modulator isotherm was used to describe the process. The equilibration constant, the stoichiometric coefficient and the column capacity for the components were calibrated. The model fitted the experimental observations well. Optimisation was achieved using a differential evolution method. As the two objective functions used in optimising the process, productivity and yield, are competing objectives, the result was not a single set point but a Pareto front.

Optimization of preparative chromatographic separation of multiple rare earth elements.

This work presents a method to optimize multi-product chromatographic systems with multiple objective functions. The system studied is a neodymium, samarium, europium, gadolinium mixture separated in an ion exchange chromatography step. A homogeneous Langmuir Mobile Phase Modified model is calibrated to fit the experiments, and then used to perform the optimization task. For the optimization a multi-objective Differential Evolution algorithm was used, with weighting based on relative value of the components to find optimal operation points along the Pareto front. The objectives of the Pareto front are weighted productivity and weighted yield with purity as an equality constraint. A prioritizing scheme based on relative values is applied for determining the pooling order. A simple rule of thumb for pooling strategy selection is presented. The multi-objective optimization gives a Pareto front which shows the rule of thumb, as a gap in one of the objective functions.

A new resorbable device for ligation of blood vessels - A pilot study.

BACKGROUND: During surgery, controlled haemostasis to prevent blood loss is vital for a successful outcome. It can be difficult to ligate vessels located deep in the abdomen. A device that is easy to use and enables secure ligatures could be beneficial. Cable ties made of nylon have been used for ligation but the non-resorbable material caused tissue reactions. The objective of this study was to use a resorbable material to construct a device with a self-locking mechanism and to test its mechanical strength and ligation efficiency. METHODS: The device was manufactured by injection moulding of polydioxanone, a resorbable polymer used for suture materials. Polydioxanone with inherent viscosities of 1.9 dL/g and 1.3 dL/g were tested. The device consisted of a perforated flexible band which could be pulled through a case with a locking mechanism. After a first version of the device had been tested, some improvements were made. The locking case was downsized, corners were rounded off, the band was made thicker and the mould was redesigned to produce longer devices. Tensile tests were performed with the second version.The first version of the device was used to ligate the ovarian pedicle in a euthanized dog and to test echogenicity of the device with ultrasound. Compression of vessels of the ovarian pedicle was examined by histology. Both versions of the device were tested for haemostasis of and tissue grip on renal arteries in six anaesthetised pigs. RESULTS: The tensile strength of the flexible band of the devices with inherent viscosity of 1.9 dL/g was 50.1 ± 5.5 N (range 35.2-62.9 N, n = 11) and the devices with inherent viscosity of 1.3 dL/g had a tensile strength of 39.8 ± 8.1 N (range 18.6-54.2 N, n = 11). Injection moulding of the polymer with lower inherent viscosity resulted in a longer flow distance.Both versions of the device had an effective tissue grip and complete haemostasis of renal arteries was verified. The device attached to the ovarian pedicle could be seen with ultrasound, and vessel compression and occlusion were verified by histology. CONCLUSIONS: Tests of functionality of the device showed complete haemostasis and good tissue grip. Devices with a band of sufficient length were easily applied and tightened in tissue.