Buttressing staples with cholecyst-derived extracellular matrix (CEM) reinforces staple lines in an ex vivo peristaltic inflation model

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ Springer Science + Business Media, LLC 2008Background - Staple line leakage and bleeding are the most common problems associated with the use of surgical staplers for gastrointestinal resection and anastomotic procedures. These complications can be reduced by reinforcing the staple lines with buttressing materials. The current study reports the potential use of cholecyst-derived extracellular matrix (CEM) in non-crosslinked (NCEM) and crosslinked (XCEM) forms, and compares their mechanical performance with clinically available buttress materials [small intestinal submucosa (SIS) and bovine pericardium (BP)] in an ex vivo small intestine model. Methods - Three crosslinked CEM variants (XCEM0005, XCEM001, and XCEM0033) with different degree of crosslinking were produced. An ex vivo peristaltic inflation model was established. Porcine small intestine segments were stapled on one end, using buttressed or non-buttressed surgical staplers. The opened, non-stapled ends were connected to a peristaltic pump and pressure transducer and sealed. The staple lines were then exposed to increased intraluminal pressure in a peristaltic manner. Both the leak and burst pressures of the test specimens were recorded. Results - The leak pressures observed for non-crosslinked NCEM (137.8 ± 22.3 mmHg), crosslinked XCEM0005 (109.1 ± 14.1 mmHg), XCEM001 (150.1 ± 16.0 mmHg), XCEM0033 (98.8 ± 10.5 mmHg) reinforced staple lines were significantly higher when compared to non-buttressed control (28.3 ± 10.8 mmHg) and SIS (one and four layers) (62.6 ± 11.8 and 57.6 ± 12.3 mmHg, respectively) buttressed staple lines. NCEM and XCEM were comparable to that observed for BP buttressed staple lines (138.8 ± 3.6 mmHg). Only specimens with reinforced staple lines were able to achieve high intraluminal pressures (ruptured at the intestinal mesentery), indicating that buttress reinforcements were able to withstand pressure higher than that of natural tissue (physiological failure). Conclusions - These findings suggest that the use of CEM and XCEM as buttressing materials is associated with reinforced staple lines and increased leak pressures when compared to non-buttressed staple lines. CEM and XCEM were found to perform comparably with clinically available buttress materials in this ex vivo model.Enterprise Irelan

Diatoms: a biotemplating approach to fabricating drug delivery reservoirs

Biotemplating is a rapidly expanding subfield that utilizes nature-inspired systems and structures to create novel functional materials, and it is through these methods that the limitations of current engineering practices may be advanced. The diatom is an exceptional template for drug delivery applications, owing largely to its highly-ordered pores, large surface area, species-specific architecture, and flexibility for surface modifications. Diatoms have been studied in a wide range of biomedical applications and their potential as the next frontier of drug delivery has yet to be fully exploited. In this editorial, the authors aim to review the use of diatoms in the delivery of poorly water-soluble drugs as reported in the literature, discuss the progress and advancements that have been made thus far, identify the shortcomings and limitations in the field, and, lastly, present their expert opinion and convey the future outlook on biotemplating approaches for drug delivery

Generating an ex vivo vascular model

Realistic ex vivo anthropometric vascular environments are required for endovascular device optimization and for preclinical evaluation of interventional procedures. The objective of this research is to build an anthropomorphic model of the human carotid artery. The combination of magnetic resonance angiography image processing and computer-aided design and manufacturing techniques allowed fabrication of multicomponent morphologically precise casts of the carotid artery. The lost core technique was used to produce a hollow vessel prototype incorporating polyvinyl alcohol cryogel (PVA-C) as a tissue-mimicking vessel wall material. PVA-C was mechanically characterized by uniaxial tensile testing after different numbers of freeze/thaw cycles. The novel model construction approach outlined in this study accounts for the morphologic complexities of the human vasculature, and proved successful for the production of realistic compliant ex vivo arterial model

Therapeutic effect of neurotrophin-3 treatment in an injectable collagen scaffold following rat spinal cord hemisection injury

Spinal cord injury (SCI) patients display varying quantities of spinal cord tissue damage with injuries that present as complete, incomplete or compressive. One theory proposed to repair the injured spinal cord and regain motor control is to regenerate axons through the lesion site. This study was designed to quantify the impact of a local injectable in situ forming hydrogel reservoir therapy following rat hemisection SCI. We investigated the effect of hydrogel only treatment following SCI in addition to hydrogels loaded with a neurotrophic factor, Neurotrophin-3 (NT-3), immediately following SCI. Functional recovery, assessed by Basso Beattie Bresnahan (BBB) locomotor test, and local healing mechanisms, including neuronal growth, glial scar formation, inflammation and collagen deposition were investigated one and 6 weeks postsurgery. Delivery of an injectable hydrogel significantly increased functional recovery at four and 6 weeks post injury. In addition, a significant reduction in the inhibitory glial scar and in inflammation was observed at the injury site. Similarly hydrogel + NT-3 delivered directly into the injury site significantly reduced glial scarring and collagen deposition. The hydrogel + NT-3 also resulted in a significant increase in neurons at 6 weeks post injury. This study represents a novel and effective therapy combining growth factor and a biomaterial based therapy following SCI.B.B. and H.K. were supported by Covidien LLC and the Industrial Development Agency (IDA) of Ireland grant. R.R. and A.K. supported by EU 7th Framework Programme Grant 304936 and CÚRAM Science Foundation Ireland (SFI) Grant 13/RC/2073. A.P. was supported by Malaysia Ministry of Education. T.S. was supported by by Covidien LLC. A.P. and S.M. were supported by CÚRAM Science Foundation Ireland (SFI) Grant 13/RC/2073.peer-reviewe

Efficacy of crosslinking on tailoring in vivo biodegradability of fibro-porous decellularized extracellular matrix and restoration of native tissue structure: a quantitative study using stereology methods

Cholecyst-derived extracellular matrix (CEM) is a fibro-porous decellularized serosal layer of porcine gall-bladder. CEM loses 90% of its weight at 48h of in vitro collagenase digestion, but takes two months to be completely resorbed in vivo. Carbodiimide (EDC) crosslinking helps tailoring CEM\u27s in vitro collagenase susceptibility. Here, the efficacy of EDC crosslinking on tailoring in vivo biodegradability of CEM is reported. CEM crosslinked with 0.0005 and 0.0033x10(3) M of EDC/mg that lose 80% and 0% of their weight respectively to in vitro collagenase digestion, were present even after 180 days in vivo. Quantitative histopathology using stereology methods confirmed our qualitative observation that even a tiny degree of crosslinking can significantly prolong the rate of in vivo degradation and removal of CEM

Rituximab therapy in steroid-resistant severe hypothyroid Grave′s ophthalmopathy

Association of Grave′s ophthalmopathy with hyperthyroidism is well known, and it has also been reported in euthyroid or hypothyroid autoimmune thyroiditis, which rarely requires treatment. Here, we report a case of bilaterally symmetrical severe corticosteroid-resistant hypothyroid Grave′s ophthalmopathy successfully treated with rituximab