Tissue Engineered Axonal Tract for Nerve Gap Bridging
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Solution Overview
Problem
Current methods for peripheral nerve injury (PNI) repair are inadequate due to the long regenerative distances and times required for axonal regeneration, leading to chronic denervation and limited functional recovery, with existing solutions like nerve guidance tubes and autografts being inferior and limited to noncritical sensory nerve injuries.
Innovation Solution
The use of tissue-engineered axonal tracts and stretch-grown tissue-engineered nerve grafts (TENGs) that mimic the structure of the lost nerve, allowing for rapid axon growth and fusion with host axons, facilitated by polyethylene glycol (PEG) to support nerve conduction and fusion, enabling effective bridging and regeneration across significant nerve gaps.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional nerve repair methods (autografts, nerve guidance tubes) are used, then nerve continuity is restored, but functional recovery is limited due to long regenerative distances and times
Solution Approach 1:
The patent applies preliminary action by pre-growing axonal tracts in a bioreactor before transplantation. Axons are cultured and extended to significant lengths (centimeters) in advance, then implanted to bridge nerve gaps. This eliminates the waiting period for axonal growth that plagues conventional methods, as the regenerative capacity is prepared beforehand and immediately deployed to the injury site.
Solution Approach 2:
The patent uses an intermediary approach by introducing tissue-engineered axonal tracts as a mediator between severed nerve ends. These engineered axons serve as a bridge that facilitates immediate connection between proximal and distal nerve stumps, rather than relying on slow endogenous regeneration. The axonal tracts act as a temporary conduit that can be integrated into the host nerve.
2Reliability
If healthy donor nerve is sacrificed for autograft, then nerve gap is bridged, but donor nerve function is lost
Solution Approach 1:
The patent applies copying by creating artificial axonal tracts that replicate the functional properties of healthy nerve axons without requiring donor tissue. Instead of harvesting axons from a healthy donor nerve, the invention synthesizes axonal structures in a bioreactor that copy the essential characteristics of native axons (structure, conductivity, regenerative capacity) using cell culture techniques and biomaterials.
Solution Approach 2:
The patent employs the principle of disposable objects by creating tissue-engineered axonal tracts that can be produced on-demand and used as single-use implants. These engineered axons serve their bridging function and can be replaced if necessary, eliminating the need for precious donor nerve tissue. The bioreactor system enables production of these temporary but effective neural conduits.
3Stability of the object's composition
If end-to-side coaptation is performed to protect distal pathway, then distal nerve structures are maintained, but donor nerve deficit occurs and procedure complexity increases
Solution Approach 1:
The patent applies extraction by removing the need for end-to-side coaptation procedures entirely. Instead of performing complex surgical maneuvers to temporarily attach donor nerve to distal stump for pathway protection, the invention directly implants engineered axonal tracts into the nerve gap. This eliminates the additional surgical steps and donor nerve requirements associated with coaptation procedures.
Data Source
AI summary
The present invention includes a composition comprising a tissue engineered axonal tract, as well as a method of making it. The invention also includes methods for treating nerve injury in a subject by contacting the site of nerve injury with a tissue engineered axonal tract, wherein the axons from the tissue engineered axonal tract fuse with axons from the subject.