Injectable Pore-Forming Hydrogels for Cell Therapy
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Solution Overview
Problem
Current biocompatible hydrogel scaffolds for cell transplantation and host cell recruitment face challenges such as inadequate pore size for cell expansion and release, and exposure to hostile host environments during inflammation, limiting their effectiveness in tissue repair and regeneration.
Innovation Solution
The development of porous hydrogels that form in situ through the degradation of sacrificial porogens, allowing controlled pore formation and cell release or recruitment, with the porogen degrading more rapidly than the bulk hydrogel, enabling mechanical support and delayed cell deployment or recruitment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If biocompatible hydrogel scaffolds are used for cell transplantation, then cell protection from host inflammatory responses is improved, but pore size is insufficient for cell expansion and release
Solution Approach 1:
The hydrogel scaffold is segmented into two distinct phases: a bulk hydrogel phase providing structural integrity and protection, and sacrificial porogen particles dispersed within it. The porogens are degraded selectively to create macropores, while the bulk hydrogel remains intact to continue protecting cells from host inflammatory responses.
Solution Approach 2:
Sacrificial porogen particles are embedded within the bulk hydrogel and subsequently extracted through selective degradation. This extraction process creates macropores within the hydrogel matrix while the bulk hydrogel structure remains intact, providing both large pores for cell expansion and continued protective encapsulation.
2Productivity
If porous hydrogels are used to facilitate cell release, then cell recruitment and release are improved, but mechanical support is reduced
Solution Approach 1:
The scaffold is divided into load-bearing bulk hydrogel and pore-forming porogen components. The bulk hydrogel maintains mechanical strength while the porogens are degraded to create pores for cell migration, separating the structural support function from the pore formation function.
Solution Approach 2:
Sacrificial porogens are pre-embedded within the bulk hydrogel before cell transplantation. The porogens degrade selectively over time to create macropores that facilitate cell migration, while the bulk hydrogel maintains mechanical support throughout the process.
3Strength
If non-porous hydrogels are used initially, then mechanical support is improved, but cell migration and recruitment are limited
Solution Approach 1:
The hydrogel scaffold transitions dynamically from a non-porous state providing mechanical support to a macroporous state facilitating cell migration. This temporal evolution is achieved through selective degradation of sacrificial porogens embedded within the bulk hydrogel over time.
Solution Approach 2:
The porosity parameter of the hydrogel changes over time through selective degradation of sacrificial porogens. Initially non-porous for mechanical support, the hydrogel develops macropores as porogens degrade, enabling cell migration while maintaining bulk structural integrity.
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 provides a biocompatible, injectable hydrogel system that supports cell expansion and tissue repair by controlling pore formation and cell release, enhancing tissue regeneration and minimizing inflammatory responses.
Implementation Method 1
the first hydrogel degrades at least 10% faster than the second hydrogel
Implementation Method 2
the first hydrogel degrades more rapidly because it is cross-linked to protease-mediated degradation motifs
Implementation Method 3
the second hydrogel is cross-linked around the first hydrogel, i.e., the porogens (first hydrogel) are completely physically entrapped in the bulk (second) hydrogel
Implementation Method 4
The composite (first and second hydrogel) composition is permeable to bodily fluids, e.g., such as enzyme which gain access to the composition to degrade the porogen hydrogel
Data Source
AI summary
The invention provides compositions and methods to form pores in situ within hydrogels following hydrogel injection. Pores formed in situ via degradation of sacrificial porogens within the surrounding hydrogel facilitate recruitment or release of cells. Disclosed herein is a material that is not initially porous, but which becomes macroporous over time.