Fibrin Sealant PolyP Preincubation Clot Stability
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Solution Overview
Problem
Current fibrin sealants do not adequately enhance the structure or resistance of fibrin clots to fibrinolysis, which can lead to suboptimal hemostasis in surgical settings.
Innovation Solution
A fibrin sealant composition comprising thrombin, fibrinogen, polyP, and calcium, where polyP is preincubated with fibrinogen and calcium to enhance clot structure and resistance to fibrinolysis, forming thicker fibrils and improving hemostatic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional fibrin sealants (thrombin and fibrinogen) are used, then hemostasis is achieved, but clot structure and resistance to fibrinolysis are insufficient
Solution Approach 1:
The patent combines fibrinogen, thrombin, polyP, and calcium ions to create a composite hemostatic sealant. This composite formulation enhances clot structure and stability beyond what conventional fibrin sealants can achieve, while maintaining biocompatibility and promoting wound healing through synergistic interactions between components.
Solution Approach 2:
The patent modifies the chemical composition parameters of the fibrin sealant by incorporating polyP and calcium ions. These parameter changes fundamentally alter the clot formation process, resulting in enhanced fibril thickness, improved clot stability, and increased resistance to fibrinolysis compared to standard formulations.
2Strength
If polyP is added to enhance clot structure, then fibril thickness and clot stability increase, but the complexity of the sealant composition increases
Solution Approach 1:
The patent employs preincubation of fibrinogen with polyP and calcium ions before adding thrombin. This preliminary action allows the formation of a pre-assembled complex that enhances fibril structure upon activation, achieving superior clot strength without requiring complex processing or multiple separate components during application.
3Reliability
If polyP is preincubated with fibrinogen and calcium, then resistance to fibrinolysis increases, but the preparation time increases
Solution Approach 1:
The preincubation step of combining fibrinogen with polyP and calcium ions creates a stable complex that requires minimal additional preparation time. This preliminary action ensures that when thrombin is added and clotting occurs, the resulting fibrin structure is already optimized for resistance to fibrinolysis, without significantly extending overall preparation time.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The inclusion of polyP in the fibrin sealant significantly increases the turbidity and resistance of fibrin clots to fibrinolysis, leading to more effective control of bleeding in surgical models, as demonstrated by reduced bleeding time and enhanced clot stability.
Implementation Method 1
Polymerization of fibrin monomers results in the formation of a semi-rigid fibrin clot
Implementation Method 2
The formation of a fibrin clot from fibrinogen is the terminal step in the coagulation cascade
Implementation Method 3
Soluble fibrin monomers, which are created when thrombin cleaves fibrinogen
Implementation Method 4
The resulting fibrin clot structure can be further stabilized via covalent cross-linking of the fibrils through the action of the transglutaminase enzyme, factor XIIIa
Implementation Method 5
Clotting of fibrinogen by thrombin is one of the few steps in the clotting cascade that does not require calcium ions
Data Source
AI summary
A fibrin sealant, comprises (a) thrombin, (b) fibrinogen, (c) polyP, and (d) calcium. The thrombin and the fibrinogen are separated prior to application.