Crosslinked Collagen and PRP Clot for Tissue Regeneration
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Solution Overview
Problem
The delivery and retention of platelet-rich plasma (PRP) at wound sites are hindered by its liquid state, leading to material loss, and current activators like bovine thrombin cause immune responses and impair clot strength, making them unsuitable for tissue regeneration.
Innovation Solution
A method involving the use of crosslinked, fibrillated collagen and calcium chloride to activate PRP, which forms a stable clot that maintains growth factor release and mechanical integrity, replacing the need for thrombin and enhancing tissue regeneration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If PRP is delivered in liquid state, then it can be easily administered, but it leads to material loss to surrounding tissues
Solution Approach 1:
The patent utilizes phase transition by converting PRP from liquid state to gel state through thrombin-induced clotting. This phase change allows the PRP to be easily injected in liquid form and then transforms into a stable gel at the application site, preventing material loss while maintaining ease of administration.
Solution Approach 2:
Thrombin serves as an intermediary substance that facilitates the transformation of PRP from liquid to gel state. The thrombin acts as a catalyst that triggers clot formation, enabling the PRP to retain its growth factors at the wound site without direct contact or complex handling procedures.
2Stability of the object's composition
If bovine thrombin is used to activate PRP, then clot formation is achieved, but immune responses and impaired clot strength occur
Solution Approach 1:
The patent extracts and removes the harmful bovine thrombin component from the PRP activation process. Instead of using external bovine thrombin that triggers immune responses, the invention relies on endogenous human thrombin already present in the PRP sample, thereby eliminating the harmful immune response while maintaining effective clot formation.
Solution Approach 2:
The PRP sample activates itself through its own endogenous thrombin content. The system is designed to utilize the patient's own thrombin within the PRP to initiate clotting, making the system self-sufficient and avoiding the need for external animal-derived thrombin that causes immune reactions.
3Stability of the object's composition
If bovine thrombin is used for clot formation, then PRP gelation increases, but cell proliferation and viability are inhibited
Solution Approach 1:
The patent removes the harmful effect of bovine thrombin on cell proliferation while retaining the beneficial gelation property. By using endogenous human thrombin instead of exogenous bovine thrombin, the system achieves adequate clot formation without the cytotoxic effects that inhibit cell proliferation and viability.
Solution Approach 2:
The invention changes the critical parameter of thrombin source from exogenous bovine to endogenous human. This parameter change maintains the gelation function necessary for clot stability while eliminating the harmful effects on cell proliferation, thereby achieving both stable clot formation and reliable cell viability.
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 collagen-based clot provides sustained release of growth factors, maintains structural integrity, and avoids immune responses, facilitating effective tissue regeneration and wound healing.
Implementation Method 1
Type I collagen in various physical states, soluble or fibrillar, was shown to be as effective as thrombin in stimulating release of TGF, PDGF and VEGF over several days
Implementation Method 2
Laci et al., Yale J Biol Med. 2010 March; 83(1): 1-9 teaches that calcium chloride may be used to activate PRP clots
Implementation Method 3
crosslinking said fibrillated collagen with N-ethyl-N'-[3-dimethylaminopropyl] carbodiimide (EDC) to generate crosslinked, fibrillated collagen
Data Source
Figure 1
Figure 2A~2D
Figure 3A
AI summary
A composition of matter is disclosed which comprises crosslinked collagen, platelet rich plasma (PRP) and an inorganic salt. Methods of generating same and uses thereof are also disclosed.