New polyoxazoline loaded patches for hemostasis in experimental liver resection

A new cost-effective NHS functionalized polyoxazoline (POx) loaded polymer with strong hemostatic properties has been developed. In this study, we investigate POx loaded hemostatic patches regarding hemostatic efficacy, local inflammatory reaction and wound-healing, as compared to the non-POx treated blanks and commercially available hemostatic products. Hundred and ten rats divided into 11 groups of 10 animals underwent partial liver lobe resection. Eight groups received experimental patches, two groups commercially available hemostatic patches (TachoSil® and Veriset™, positive controls), one group with gauzes (negative control). Each animal received twice a patch with a size 1.5 × 2.5 cm, on each partially resected lobe. Primary endpoint was time to hemostasis (TTH). The rats were sacrificed at different time points (1, 3, or 7 days) to measure local inflammatory response and early wound healing. Of the POx loaded patches, GFC NHS-POx (TTH 20.4 s, p = .019) and GFC-NHS-POx1.5 (TTH 0.0 s, p = .003) showed significantly faster TTH compared to TachoSil® (TTH 95.4 s), and were comparable to Veriset™ (TTH 17.0 s). Three patches, GFC-NHS-POx 1.5 (TTH 0.0 s, p = .016), ORC NHS-POx:NU-POx (TTH 91.4 s, p = .033), and ORC-PLGA NHS-POx:NU-POx (TTH 105.6 s, p = .04) had a lower TTH compared to their own blank carrier (TTH 74.9, 157.8, and 195.7 s, respectively). With regard to biocompatibility, all POx loaded patches showed results comparable to TachoSil® and Veriset™. NHS-POx-loaded hemostatic patch demonstrate fast and effective hemostasis, comparable or better than commercially available hemostatic patches, with similar early biocompatibility

Efficacy of a novel polyoxazoline-based hemostatic patch in liver and spleen surgery.

BACKGROUND: A new hemostatic sealant based on a N-hydroxy-succinimide polyoxazoline (NHS-POx) polymer was evaluated to determine hemostatic efficacy and long-term wound healing and adverse effects in a large animal model of parenchymal organ surgical bleeds. METHODS: Experiment 1 included 20 pigs that were treated with two NHS-POx patch prototypes [a gelatin fibrous carrier (GFC) with NHS-POx and an oxidized regenerated cellulose (ORC) with poly(lactic-co-glycolic acid)-NHS-POx:NU-POx (nucleophilically activated polyoxazoline)], a blank gelatin patch (GFC Blank), TachoSil(®) and Veriset™ to stop moderate liver and spleen punch bleedings. After various survival periods (1-6 weeks), pigs were re-operated to evaluate patch degradation and parenchymal healing. During the re-operation, experiment 2 was performed: partial liver and spleen resections with severe bleeding, and hemostatic efficacy was evaluated under normal and heparinized conditions of the two previous prototypes and one additional NHS-POx patch. In the third experiment an improved NHS-POx patch (GATT-Patch; GFC-NHS-POx and added 20% as nucleophilically activated polyoxazoline; NU-POx) was compared with TachoSil(®), Veriset™ and GFC Blank on punch bleedings and partial liver and spleen resections for rapid (10s) hemostatic efficacy. RESULTS: NHS-POx-based patches showed better (GFC-NHS-POx 83.1%, ORC-PLGA-NHS-POx: NU-POx 98.3%) hemostatic efficacy compared to TachoSil(®) (25.0%) and GFC Blank (43.3%), and comparable efficacy with Veriset™ (96.7%) on moderate standardized punch bleedings on liver and spleen. All patches demonstrated gradual degradation over 6 weeks with a reduced local inflammation rate and an improved wound healing. For severe bleedings under non-heparinized conditions, hemostasis was achieved in 100% for Veriset™, 40% for TachoSil and 80-100% for the three NHS-POx prototypes; similar differences between patches remained for heparinized conditions. In experiment 3, GATT-Patch, Veriset™, TachoSil and GFC Blank reached hemostasis after 10s in 100%, 42.8%, 7.1% and 14.3%, respectively, and at 3 min in 100%, 100%, 14.3% and 35.7%, respectively, on all liver and spleen punctures and resections. CONCLUSIONS: NHS-POx-based patches, and particularly the GATT-Patch, are fast in achieving effective hemostatic sealing on standardized moderate and severe bleedings without apparent long-term adverse events

Tubular collagen scaffolds with radial elasticity for hollow organ regeneration

Contains fulltext : 174175.pdf (publisher's version ) (Closed access)Tubular collagen scaffolds have been used for the repair of damaged hollow organs in regenerative medicine, but they generally lack the ability to reversibly expand in radial direction, a physiological characteristic seen in many native tubular organs. In this study, tubular collagen scaffolds were prepared that display a shape recovery effect and therefore exhibit radial elasticity. Scaffolds were constructed by compression of fibrillar collagen around a star-shaped mandrel, mimicking folds in a lumen, a typical characteristic of empty tubular hollow organs, such as ureter or urethra. Shape recovery effect was introduced by in situ fixation using a star-shaped mandrel, 3D-printed clamps and cytocompatible carbodiimide crosslinking. Prepared scaffolds expanded upon increase of luminal pressure and closed to the star-shaped conformation after removal of pressure. In this study, we applied this method to construct a scaffold mimicking the dynamics of human urethra. Radial expansion and closure of the scaffold could be iteratively performed for at least 1000 cycles, burst pressure being 132+/-22mmHg. Scaffolds were seeded with human epithelial cells and cultured in a bioreactor under dynamic conditions mimicking urination (pulse flow of 21s every 2h). Cells adhered and formed a closed luminal layer that resisted flow conditions. In conclusion, a new type of a tubular collagen scaffold has been constructed with radial elastic-like characteristics based on the shape of the scaffold, and enabling the scaffold to reversibly expand upon increase in luminal pressure. These scaffolds may be useful for regenerative medicine of tubular organs. STATEMENT OF SIGNIFICANCE: In this paper, a new type I collagen-based tubular scaffold is presented that possesses intrinsic radial elasticity. This characteristic is key to the functioning of a number of tubular organs including blood vessels and organs of the gastrointestinal and urogenital tract. The scaffold was given a star-shaped lumen by physical compression and chemical crosslinking, mimicking the folding pattern observed in many tubular organs. In rest, the lumen is closed but it opens upon increase of luminal pressure, e.g. when fluids pass. Human epithelial cells seeded on the luminal side adhered well and were compatible with voiding dynamics in a bioreactor. Collagen scaffolds with radial elasticity may be useful in the regeneration of dynamic tubular organs