The development of hemostatic technologies that suit a diverse range of emergency scenarios is a critical initiative, and there is an increasing interest in the development of absorbable dressings that can be left in the injury site and degrade to reduce the duration of interventional procedures. In the current study, β-cyclodextrin polyester (CDPE) hydrogels serve as sacrificial macroporous carriers, capable of degradation under physiological conditions. The CDPE template enables the assembly of imprinted chitosan honeycomb-like monolithic mats, containing highly entangled nanofibers with diameters of 9.2 ± 3.7 nm, thereby achieving an increase in the surface area of chitosan to improve hemostatic efficiency. In vivo, chitosan-loaded cyclodextrin (CDPE-Cs) hydrogels yield significantly lower amounts of blood loss and shorter times to hemostasis compared with commercially available absorbable hemostatic dressings, and are highly biocompatible. The designed hydrogels demonstrate promising hemostatic efficiency, as a physiologically-benign approach to mitigating blood loss in tissue-injury scenarios. Sacrificial templates are used for a range of different applications. Here, the authors synthesise a hyperbranched cyclodextrin polyester template with large void spaces, which is degraded in physiological conditions, and use it to create high surface area chitosan scaffolds for haemostatic applications.

/pdf/absorbable-hemostatic-hydrogels-comprising-composites-of-26rud2ag4b.pdf

Absorbable hemostatic hydrogels comprising composites of sacrificial templates and honeycomb-like nanofibrous mats of chitosan.

Animal models of hemostasis are often extrapolated to humans; however, only a few studies have compared coagulation and fibrinolysis across species. Simultaneous thrombin (TG) and plasmin (PG) generation is useful to assessing coagulation and fibrinolysis within the same sample. In this study, we performed simultaneous TG and PG analysis in blood plasma samples from humans and 6 species commonly evaluated in pre-clinical research. TG and PG were investigated in male and female donor platelet-poor plasmas (PPP) obtained from 28 healthy humans, 10 baboons, 12 rhesus monkeys, 20 Yorkshire pigs, 20 Sprague-Dawley rats, 10 New Zealand White rabbits and 14 Hartley guinea pigs. The continuous generation of the 7-amino-4-methylcoumarin (AMC) from substrates specific to thrombin or plasmin was monitored. The thrombin and plasmin concentration peak heights (PH) and production rates (PR) were calculated. TG and PG parameters from baboon and rhesus macaque plasma approximated that of humans. The other species differed significantly from both human and non-human primates. For example, swine and rat plasmas demonstrated similar TG, but swine plasmas did not generate plasmin. TG and PG parameters from Guinea pig samples were extremely low, while rabbit plasmas showed variable PG curves demonstrating one or two peaks with low and high PR values, respectively. Correlations between PH and PR values were significant with the exceptions of human PG, baboon TG, rat TG and Guinea pig PG. These findings are informative to pre-clinical animal species selection and optimization of coagulation and fibrinolysis translational research.

/pdf/interspecies-comparison-of-simultaneous-thrombin-and-plasmin-1dfxg6v49v.pdf

Interspecies comparison of simultaneous thrombin and plasmin generation.

Animal tests are conducted in all fields of trauma research, but transferability of these data to humans is limited. For example, it is still unclear which animal species is most similar to humans in terms of physiology of blood coagulation. To improve transferability and raise awareness of the existing differences, we compared human coagulation to coagulation of different animals. Rotational thromboelastometry was used to analyse the blood of pigs, sheep, rabbits and dogs. Animal data were compared with human coagulation based on the number of significant differences of the test parameters and on a descriptive comparison of the extent of relative deviation of the single values. All animal species showed significant differences in coagulation properties when compared with humans. Coagulation parameters of dogs and sheep were on average most similar to humans. However, there is no animal which is most similar to humans concerning all aspects of coagulation. Differences in coagulation between humans and animals are significant. This must be taken into account when transferring animal test data to humans.

https://militaryhealth.bmj.com/content/jramc/165/5/356.full.pdf

In-vitro study of species-specific coagulation differences in animals and humans using rotational thromboelastometry (ROTEM)

Determination of reference intervals for single vial rotational thromboelastometry (ROTEM) parameters and correlation with plasmatic coagulation times in 49 clinically healthy dogs

Designing usable forms of topical haemostatic agents is the most important activity during the design process, resulting in strengthened functional properties of the final medical devices. This study aimed to propose indications for a research programme based on risk management supporting the development of two usable forms of a topical haemostatic agent: chitosan/alginate lyophilized foam and chitosan/alginate impregnated gauze. Both of the usable forms of the topical haemostatic agent, being the main part of the modified combat gauze, were fabricated using the chitosan/alginate complex. Risk analysis is helpful in developing an appropriate research programme, significantly reducing the risk to an acceptable level.

Design of New-Generation Usable Forms of Topical Haemostatic Agents Containing Chitosan.

Objectives: Hemorrhage is the leading cause of preventable death in military conflicts. Different types of hemostatic dressings have been compared in animal studies for their ability to control bleeding. However, the effects of hemostatic agents in animals may be different from those in humans. The aim of this study was to assess the efficacy of hemostatic dressings in human blood. Methods: Clotting time, clot formation time, α-angle, maximum clot firmness, and lysis index of human blood incubated with QuikClot Gauze, Celox Gauze, QuikClot ACS+, and standard gauze, were compared using rotational thromboelastometry (ROTEM). Nonactivated, intrinsically activated, extrinsically activated, and fibrin-based ROTEM were used to elucidate different mechanisms of action of those dressings. Results: QuikClot Gauze was the most efficacious hemostatic dressing, followed by Celox Gauze and standard gauze. QuikClot ACS+ was clearly outperformed. Conclusions: Modern hemostatic dressings such as QuikClot Gauze an...

Efficacy of Hemostatic Agents in Humans With Rotational Thromboelastometry: An in-vitro Study

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In-vitro study of species-specific coagulation differences in animals and humans using rotational thromboelastometry (ROTEM)

Efficacy of Hemostatic Agents in Humans With Rotational Thromboelastometry: An in-vitro Study