Implantable Particles With Modified Shells for Reduced Foreign Body Response
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Solution Overview
Problem
Existing implanted particles face challenges in minimizing the foreign body response (FBR) due to their biocompatibility issues, which affect their performance and longevity.
Innovation Solution
The development of particles comprising a first compartment surrounded by a second compartment, with a compound of Formula (I) and a hydrogel-forming polymer, such as alginate, that are chemically modified to mitigate the FBR, allowing for a more afibrotic response and improved cell encapsulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If particles are implanted to deliver therapeutic agents, then therapeutic effect is improved, but foreign body response (FBR) increases
Solution Approach 1:
The patent applies local quality by chemically modifying only the outer shell of the particle with specific compounds (such as polyethylene glycol or hydrophilic polymers) to create an afibrotic surface, while the inner core maintains its therapeutic payload. This localized modification reduces FBR at the particle-tissue interface without altering the therapeutic function, thereby resolving the contradiction between therapeutic effectiveness and immune response mitigation.
Solution Approach 2:
The patent employs composite materials by combining a core material (containing therapeutic agents or cells) with a shell material (chemically modified with afibrotic compounds). This composite structure allows the particle to simultaneously provide therapeutic function through the core and reduce foreign body response through the modified shell, effectively resolving the technical contradiction between therapeutic efficacy and biocompatibility.
2Object-affected harmful factors
If particle size is increased to reduce FBR, then biocompatibility is improved, but cell encapsulation capacity decreases
Solution Approach 1:
The patent applies the nested doll principle by creating a core-shell structure where the inner core contains high concentrations of encapsulated cells or therapeutic payloads, while the outer shell provides the afibrotic protective layer. This nesting allows the particle to maintain a compact size that can still encapsulate sufficient cells in the core, while the shell's chemical modification reduces fibrotic response, thereby resolving the contradiction between biocompatibility and encapsulation capacity.
3Object-affected harmful factors
If chemical modification is applied to mitigate FBR, then biocompatibility is improved, but manufacturing complexity increases
Solution Approach 1:
The patent applies preliminary action by pre-synthesizing the afibrotic shell material or pre-coating the particle core with modified polymers before final particle assembly. This preliminary preparation of the biocompatible layer allows for standardized manufacturing processes, reducing the complexity that would otherwise arise from performing chemical modifications after particle formation. The approach enables batch production of modified particles while maintaining consistent biocompatibility properties.
Data Source
AI summary
Described herein are particles comprising a first compartment, a second compartment, and a compound of Formula (I), as well as compositions and methods of making and using the same. The particles may comprise a cell capable of expressing a therapeutic agent useful for the treatment of a disease, disorder, or condition described herein.