Recent Advances in Blood Cell-Inspired and Clot-Targeted Thrombolytic Therapies

Sheridan, Anastasia; Brown, Ashley

doi:10.1155/2023/6117810

Cited by 3 publications

(3 citation statements)

References 83 publications

(126 reference statements)

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“…Hydrogels with photocurable linkers have been widely used for implants and in tissue engineering, and there are some examples of their successful use in microrobotics. ,− However, applications of microrobots made from hydrogels are limited due to the swelling and relatively low mechanical strength of hydrogels. Given the challenge of designing biodegradable materials that enable complex task performance, we list a handful of synthetic polymers from the drug delivery and tissue engineering communities that are promising for making microrobots due to their history of use, biodegradation, hydrophobicity, and photocurable properties (Table ).…”

Section: Methodsmentioning

confidence: 99%

Microrobots for Biomedicine: Unsolved Challenges and Opportunities for Translation

et al. 2023

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Microrobots are being explored for biomedical applications, such as drug delivery, biological cargo transport, and minimally invasive surgery. However, current efforts largely focus on proof-of-concept studies with nontranslatable materials through a "design-and-apply" approach, limiting the potential for clinical adaptation. While these proof-of-concept studies have been key to advancing microrobot technologies, we believe that the distinguishing capabilities of microrobots will be most readily brought to patient bedsides through a "design-by-problem" approach, which involves focusing on unsolved problems to inform the design of microrobots with practical capabilities. As outlined below, we propose that the clinical translation of microrobots will be accelerated by a judicious choice of target applications, improved delivery considerations, and the rational selection of translation-ready biomaterials, ultimately reducing patient burden and enhancing the efficacy of therapeutic drugs for difficult-to-treat diseases.

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Section: Methodsmentioning

confidence: 99%

Microrobots for Biomedicine: Unsolved Challenges and Opportunities for Translation

et al. 2023

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“…Therefore, targeted therapeutic delivery methods for anticoagulants and hemostatic therapies could restore hemostatic balance more effectively in DIC patients than systemic delivery. Fortunately, clots provide multiple targeting moieties that drug delivery methods can take advantage of, such as activated platelets and fibrin . Here, we developed fibrin-targeted nanogels to deliver anticoagulants and other hemostatic therapies that restore hemostatic balance in DIC patients more effectively than systemic delivery.…”

Section: Introductionmentioning

confidence: 99%

“…Fortunately, clots provide multiple targeting moieties that drug delivery methods can take advantage of, such as activated platelets and fibrin. 19 Here, we developed fibrin-targeted nanogels to deliver anticoagulants and other hemostatic therapies that restore hemostatic balance in DIC patients more effectively than systemic delivery.…”

Section: Introductionmentioning

confidence: 99%

Clot-Targeted Nanogels for Dual-Delivery of AntithrombinIII and Tissue Plasminogen Activator to Mitigate Disseminated Intravascular Coagulation Complications

Sheridan,

Nellenbach,

Pandit

et al. 2024

ACS Nano

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Disseminated intravascular coagulation (DIC) is a pathologic state that follows systemic injury and other diseases. Often a complication of sepsis or trauma, DIC causes coagulopathy associated with paradoxical thrombosis and hemorrhage. DIC upregulates the thrombotic pathways while simultaneously downregulating the fibrinolytic pathways that cause excessive fibrin deposition, microcirculatory thrombosis, multiorgan dysfunction, and consumptive coagulopathy with excessive bleeding. Given these opposing disease phenotypes, DIC management is challenging and includes treating the underlying disease and managing the coagulopathy. Currently, no therapies are approved for DIC. We have developed clot-targeted therapeutics that inhibit clot polymerization and activate clot fibrinolysis to manage DIC. We hypothesize that delivering both an anticoagulant and a fibrinolytic agent directly to clots will inhibit active clot polymerization while also breaking up pre-existing clots; therefore, reversing consumptive coagulopathy and restoring hemostatic balance. To test this hypothesis, we single-and dual-loaded fibrin-specific nanogels (FSNs) with antithrombinIII (ATIII) and/or tissue plasminogen activator (tPA) and evaluated their clot preventing and clot lysing abilities in vitro and in a rodent model of DIC. In vivo, single-loaded ATIII-FSNs decreased fibrin deposits in DIC organs and reduced blood loss when DIC rodents were injured. We also observed that the addition of tPA in dual-loaded ATIII-tPA-FSNs intensified the antithrombotic and fibrinolytic mechanisms, which proved advantageous for clot lysis and restoring platelet counts. However, the addition of tPA may have hindered wound healing capabilities when an injury was introduced. Our data supports the benefits of delivering both anticoagulants and fibrinolytic agents directly to clots to reduce the fibrin load and restore hemostatic balance in DIC.

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Perspective/Commentary: The Transformation of STEMI Care with Thrombolysis in Paramedicine

Maria

2024

Intensive Care Res

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The integration of thrombolysis into paramedicine practice has brought about a significant paradigm shift in the treatment and prognosis of patients with STEMI (ST-Elevation Myocardial Infarction). This innovative approach has led to a notable increase in patient survival rates, demonstrating its effectiveness. A crucial aspect of this transformative change is the noteworthy reduction in “door-to-needle” time, a critical benchmark in STEMI management. As we delve deeper into examining this shift, it becomes increasingly evident that its impact extends beyond the immediate and convenient on-scene medical intervention. Instead, it fundamentally alters the trajectory of patient outcomes, highlighting the evolving role of paramedicine within the realm of medical care.

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Recent Advances in Blood Cell-Inspired and Clot-Targeted Thrombolytic Therapies

Cited by 3 publications

References 83 publications

Microrobots for Biomedicine: Unsolved Challenges and Opportunities for Translation

Microrobots for Biomedicine: Unsolved Challenges and Opportunities for Translation

Clot-Targeted Nanogels for Dual-Delivery of AntithrombinIII and Tissue Plasminogen Activator to Mitigate Disseminated Intravascular Coagulation Complications

Perspective/Commentary: The Transformation of STEMI Care with Thrombolysis in Paramedicine

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