Fibrinogen-Depleted Platelet Releasate Preparation
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Solution Overview
Problem
Current methods for preparing platelet-derived growth factors face challenges in achieving optimal yield while minimizing the risk of pathogens, including both enveloped and non-enveloped viruses, bacteria, and other blood-borne microorganisms, and are insufficient for clinical applications in regenerative medicine and wound healing.
Innovation Solution
A method involving consecutive steps of pathogen concentration reduction, activation to release alpha granules, fibrinogen depletion, and further pathogen reduction, followed by sterile filtration and lyophilization, to produce a fibrinogen-depleted platelet releasate with enhanced safety and efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If platelets are subjected to lyophilization with preservatives (DMSO, trehalose, cryoprotectant compositions), then platelet preservation is improved, but proteins, receptors and other bioactive components are retained on the platelet surface or within the platelets, increasing the risk of unwanted interactions with extracellular factors
Solution Approach 1:
The patent applies the extraction principle by removing platelets from the blood sample through centrifugation, isolating them in a separate fraction. This allows subsequent processing of the isolated platelets without the interfering presence of other blood components, enabling controlled lysis and growth factor release while minimizing unwanted interactions
Solution Approach 2:
The patent utilizes parameter changes by adjusting pH levels (to 7.0-9.0) and temperature (2-50°C) during the lysis process. These controlled parameter modifications optimize the disruption of platelet membranes and release of growth factors while maintaining product safety and stability
2Adaptability or versatility
If platelet concentrates are prepared using autologous PRP from patient's own blood, then applicability in regenerative medicine is improved, but the need for a dedicated machine or laboratory increases complexity and the growth factors lose bioactivity after a few hours
Solution Approach 1:
The patent applies segmentation by dividing the blood processing into distinct functional steps: platelet separation, activation/lysis, growth factor release, and filtration. This modular approach allows each step to be optimized independently and can be performed using standard laboratory equipment rather than requiring complex dedicated machines
Solution Approach 2:
The patent implements preliminary action by pre-isolating and concentrating platelets before the actual therapeutic application. The platelet concentrate can be prepared in advance and stored, with growth factors released upon needed activation, eliminating the need for dedicated machines at the point of use
3Productivity
If platelet concentrates are prepared from expired platelet stocks, then availability and productivity are improved, but the risk of pathogen transmission increases
Solution Approach 1:
The patent converts the potential harm of pathogen transmission into a benefit by implementing multiple filtration stages (including 0.22 µm filters) and pathogen reduction steps. These measures, while adding process complexity, enable the safe use of expired platelet stocks by systematically eliminating or inactivating pathogens
Solution Approach 2:
The patent introduces intermediary filtration systems and pathogen reduction treatments as intermediate steps between platelet isolation and final product. These intermediary measures act as barriers that prevent pathogen transmission while allowing the utilization of expired platelet stocks
4Quantity of substance
If platelets are activated to release alpha granule content, then growth factor availability is improved, but the process must be completed within a few hours or growth factors lose bioactivity
Solution Approach 1:
The patent applies preliminary action by pre-isolating platelets and preparing them in a stable concentrated form. The platelet concentrate can be stored with growth factors intact, and activation is performed only when needed, extending the time window beyond the natural 2-3 hour limitation
Solution Approach 2:
The patent utilizes parameter changes by controlling pH (7.0-9.0) and temperature (2-50°C) during the lysis and activation process. These controlled conditions optimize growth factor release while maintaining stability and preventing degradation, effectively extending the operational time window
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
This method achieves a high yield of growth factors with minimal pathogen risk, ensuring safety and efficacy for therapeutic use, including regenerative medicine and cell culture applications, and allows for the use of expired platelet stocks, thereby addressing the limitations of existing technologies.
Implementation Method 1
subjecting the platelet concentrate to a first pathogen concentration reduction step with the purpose of disrupting both DNA and RNA of micro-organisms present in the platelet concentrate
Implementation Method 2
subjecting the platelet concentrate to an activation step by contacting it with an activating agent to cause the platelets to release at least part of alpha granules and growth factors present therein
Implementation Method 3
subjecting the fluid platelet releasate to a fibrinogen concentration reduction step and recovering a fibrinogen depleted fluid platelet releasate
Implementation Method 4
subjecting the fibrinogen depleted fluid platelet releasate to a second pathogen concentration reduction step with the purpose of disrupting enveloped viruses
Implementation Method 5
subjecting the platelet releasate to sterile filtering and recovering from the filtering step a filtrate liquid containing the growth factors
Implementation Method 6
subjecting the thus obtained individual portions of filtrate liquid to lyophilisation
Data Source
AI summary
The present invention relates to a method for preparing a growth-factors containing platelet releasate from a fluid mammalian platelet concentrate, comprising the consecutive steps of subjecting the platelet concentrate to a pathogen reduction step to disrupt non-enveloped viruses; subjecting the platelet concentrate to an activation step to cause the platelets to release growth factors; recovering a fibrinogen depleted fluid platelet releasate; subjecting the fibrinogen depleted fluid platelet releasate to a second pathogen concentration reduction step to disrupt enveloped viruses; subjecting the platelet releasate to sterile filtering and recovering a filtrate liquid containing the growth factors. The platelet releasate obtained with the method of the present invention may be used as a therapeutic agent to enhance the proliferation of multi lineage cells in regenerative medicine and in the management of non healing wounds and resistant ulcers. The second indication is as a substitute to fetal bovine serum in in cell culture media.