Post-Fabrication PEU Functionalization via Click Chemistry
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Solution Overview
Problem
Current methods for attaching bioactive molecules to amino acid-based poly(ester ureas) often result in denaturation or degradation, especially when done before the polymer is processed into its final form, limiting their biological activity and functionality.
Innovation Solution
Development of tyrosine-based poly(ester ureas) functionalized with pendent functional groups that can bond with bioactive molecules via click reactions after the polymer has been processed, utilizing monomers with specific structures and click chemistry methods to attach bioactive compounds such as peptides and growth factors post-fabrication.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If bioactive molecules are attached to PEU prior to processing, then the polymer can be fabricated into desired forms, but the biological activity is lost due to denaturation or degradation
Solution Approach 1:
The patent incorporates reactive functional groups (azide or alkyne) into the PEU polymer chain during synthesis, preparing the polymer in advance for post-fabrication conjugation. This preliminary action enables the polymer to be first fabricated into the desired form, then subsequently conjugated with bioactive molecules under mild conditions that preserve biological activity, thus resolving the contradiction between fabrication ease and biological activity preservation
Solution Approach 2:
The patent employs click chemistry reactions that operate under mild parameters (ambient temperature, aqueous conditions, short reaction times) for post-fabrication conjugation. These parameter changes allow the bioactive molecules to be attached after the polymer is formed, avoiding the high temperatures and harsh conditions of traditional pre-fabrication conjugation methods that cause denaturation, thereby preserving biological activity while maintaining fabrication flexibility
2Ease of manufacture
If conventional methods are used to attach bioactive molecules before processing, then conjugation can be achieved, but the bioactive molecules undergo denaturation or degradation
Solution Approach 1:
The patent uses click chemistry reactions (azide-alkyne cycloaddition) as an intermediary mechanism to conjugate bioactive molecules to PEU. This intermediary reaction pathway operates under mild conditions that are compatible with bioactive molecule stability, unlike conventional coupling methods that require harsh conditions. The click chemistry acts as a bridge that enables conjugation without compromising biological activity, thus resolving the contradiction between ease of manufacture and reliability
3Reliability
If reactive sites are incorporated into PEU for post-fabrication functionalization, then bioactive molecules can be attached after processing, but additional functionalization steps are required
Solution Approach 1:
The patent incorporates universal reactive functional groups (azide or alkyne) into the PEU polymer structure that can participate in multiple types of click chemistry reactions. This universality allows the same functionalized PEU to be conjugated with various different bioactive molecules (peptides, proteins, drugs) using the same reaction chemistry, thereby reducing the overall process complexity despite the additional functionalization step. The multi-functionality of the reactive groups simplifies the functionalization process rather than increasing it
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 approach allows for the efficient and stable attachment of bioactive molecules to poly(ester ureas post-fabrication, preserving their biological activity and enabling the creation of functionalized polymers for biomedical applications with enhanced biological interactions.
Implementation Method 1
tyrosine-based poly(ester ureas) functionalized with pendent functional groups that can bond with bioactive molecules via click reactions
Data Source
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AI summary
Amino acid-based poly(ester urea)s (PEU) are emerging as a class of polymers that have shown promise in regenerative medicine applications. Embodiments of the invention relate to the synthesis of PEUs carrying pendent "clickable" groups on modified tyrosine amino acids. The pendent species include alkyne, azide, alkene, tyrosine-phenol, and ketone groups. PEUs with Mw exceeding 100k Da were obtained via interfacial polycondensation methods and the concentration of pendent groups was varied by copolymerization. The incorporation of derivatizable functionalities is demonstrated using 1H NMR and UV-Vis spectroscopy methods. Electrospinning was used to fabricate PEU nanofibers with a diameters ranging from 350 nm to 500 nm. The nanofiber matricies possess mechanical strengths suitable for tissue engineering (Young's modulus: 30045 MPa; tensile stress: 8.51.2 MPa). A series of bioactive peptides and fluorescent molecules were conjugated to the surface of the nanofibers following electrospinning using bio-orthogonal reactions in aqueous media.