Intravenous hemostats: challenges in translation to patients

Lashof-Sullivan, Margaret; Shoffstall, Andrew J.; Lavik, Erin B.

doi:10.1039/c3nr03595f

Cited by 30 publications

(37 citation statements)

References 96 publications

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“…Detailed discussions of these systems are beyond the scope of the current review, but several informative reviews on many of these systems are available elsewhere. 178,[186][187][188]…”

Section: Platelet Substitutes Synthetic Hemostats and Platelet-inspmentioning

confidence: 99%

Bio‐inspired nanomedicine strategies for artificial blood components

Gupta

2017

WIREs Nanomed Nanobiotechnol

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Blood is a fluid connective tissue where living cells are suspended in non-cellular liquid matrix. The cellular components of blood render gas exchange (RBCs), immune surveillance (WBCs) and hemostatic responses (platelets), and the non-cellular components (salts, proteins etc.) provide nutrition to various tissues in the body. Dysfunction and deficiencies in these blood components can lead to significant tissue morbidity and mortality. Consequently, transfusion of whole blood or its components is a clinical mainstay in the management of trauma, surgery, myelosuppression and congenital blood disorders. However, donor-derived blood products suffer from issues of shortage in supply, need for type matching, high risks of pathogenic contamination, limited portability and shelf-life, and a variety of side-effects. While robust research is being directed to resolve these issues, a parallel clinical interest has developed towards bioengineering of synthetic blood substitutes that can provide blood’s functions while circumventing the above problems. Nanotechnology has provided exciting approaches to achieve this, using materials engineering strategies to create synthetic and semi-synthetic RBC substitutes for enabling oxygen transport, platelet substitutes for enabling hemostasis and WBC substitutes for enabling cell-specific immune response. Some of these approaches have further extended the application of blood cell-inspired synthetic and semi-synthetic constructs for targeted drug delivery and nanomedicine. The current article will provide a comprehensive review of the various nanotechnology approaches to design synthetic blood cells, along with a critical discussion of successes and challenges of the current state-of-art in this field.

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“…Detailed discussions of these systems are beyond the scope of the current review, but several informative reviews on many of these systems are available elsewhere. 178,[186][187][188]…”

Section: Platelet Substitutes Synthetic Hemostats and Platelet-inspmentioning

confidence: 99%

Bio‐inspired nanomedicine strategies for artificial blood components

Gupta

2017

WIREs Nanomed Nanobiotechnol

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“…However, there has been a lack of successful treatments for internal bleeding. Research has spanned methods ranging from blood products, cell-derived particles, drugs that interact with the clotting cascade, to synthetic materials 7 . Cell-derived products include thromboerythrocytes, thrombosomes, and synthocytes that involve modification of cell-derived materials with fibrinogen or peptides to augment clotting 8–10 .…”

Section: Introductionmentioning

confidence: 99%

Hemostatic Nanoparticles Improve Survival Following Blunt Trauma Even after 1 Week Incubation at 50 °C

Lashof-Sullivan

Mark

Groynom

et al. 2016

ACS Biomater. Sci. Eng.

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According to the CDC, the leading cause of death for both men and women between the ages of 5 and 44 is traumatic injury. Blood loss is the primary cause of death at acute time points post trauma. Early intervention is critical to save lives, and yet there are no treatments to stop internal bleeding that can be deployed in the field. In this work, we developed hemostatic nanoparticles that are stable at high temperatures (50 °C for 7 days) and are still effective at stopping bleeding and improving survival over the one hour time period in a rat liver injury model. These particles are exceptionally simple: PLA-based nanospheres functionalized with PEG terminated with variants of the RGD motif. This simple system can be stored at temperatures up to 50°C and maintain size, shape, and efficacy. The particles lead to a reduction in bleeding and increased acute survival with significance compared to both control particles and saline. Overall, these hemostatic nanoparticles offer an important step towards an immediate intervention in the field to stop bleeding and improve survival.

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“…Synthetic platelet substitutes can potentially resolve many issues that currently complicate platelet transfusion [13,14,33,34]. Several previous 'synthetic platelet' designs have focused on amplifying the 'platelet aggregation' mechanism by coating synthetic particles with Fg or Fgrelevant peptides, but have not yet been translated into clinical application [35][36][37].…”

Section: Discussionmentioning

confidence: 99%

In vitro characterization of SynthoPlate™ (synthetic platelet) technology and its in vivo evaluation in severely thrombocytopenic mice

Shukla

Sekhon

Betapudi

et al. 2017

Journal of Thrombosis and Haemostasis

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Summary Background Platelet transfusion applications face severe challenges due to the limited availability and portability, high risk of contamination and short shelf-life of platelets. Therefore there is significant interest in synthetic platelet substitutes that can render hemostasis while avoiding these issues. Platelets promote hemostasis by injury site-selective adhesion and aggregation, and propagation of coagulation reactions on their membrane. Based on these mechanisms, we have developed a synthetic platelet technology (SynthoPlateTM) that integrates platelet-mimetic site-selective ‘adhesion’ and ‘aggregation’ functionalities via heteromultivalent surface-decoration of lipid vesicles with Von Willebrand Factor-binding, collagen-binding and active platelet integrin GPIIb-IIIa-binding peptides. Objective SynthoPlateTM was evaluated for its effects on platelets and plasma in vitro, and for systemic safety and hemostatic efficacy in severely thrombocytopenic mice in vivo. Methods In vitro, SynthoPlateTM was evaluated using aggregometry, fluorescence microscopy, microfluidics, and thrombin and fibrin generation assays. In vivo, SynthoPlateTM was evaluated for systemic safety using prothrombin and fibrin assays on plasma and for hemostatic effect on tail-transection bleeding time in severely thrombocytopenic (TCP) mice. Results SynthoPlateTM did not aggregate resting platelets or spontaneously promote coagulation in plasma, but could amplify recruitment and aggregation of active platelets at the bleeding site and thereby site-selectively enhance fibrin generation. SynthoPlateTM dose-dependently reduced bleeding time in TCP mice, to levels comparable to normal mice. SynthoPlateTM has a reasonable circulation residence time and is cleared mostly by the liver and spleen. Conclusion The results demonstrate the promise of SynthoPlateTM as a synthetic platelet substitute in transfusion treatment of platelet-related bleeding complications.

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Intravenous hemostats: challenges in translation to patients

Cited by 30 publications

References 96 publications

Bio‐inspired nanomedicine strategies for artificial blood components

Bio‐inspired nanomedicine strategies for artificial blood components

Hemostatic Nanoparticles Improve Survival Following Blunt Trauma Even after 1 Week Incubation at 50 °C

In vitro characterization of SynthoPlate™ (synthetic platelet) technology and its in vivo evaluation in severely thrombocytopenic mice

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