MAP Scaffold Delivery of Dissociated Islet Cells Without Preconditioning
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Solution Overview
Problem
The scarcity of donor islets for pancreatic islet transplantation and the need for pre-conditioning of dissociated islets prior to implantation pose challenges in effectively treating Type 1 diabetes.
Innovation Solution
The use of a microporous annealed particle (MAP) scaffold to deliver enzymatically dissociated islet cells, which allows for the encapsulation of insulin-releasing pancreatic islet cells, providing a viable alternative to traditional transplantation methods without the need for pre-conditioning.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If dissociated islet cells are delivered without pre-conditioning, then the treatment time is reduced and productivity is improved, but the reliability of cell survival and function deteriorates
Solution Approach 1:
The scaffold is pre-engineered with microporous structures and bioactive molecules before cell delivery, creating a pre-conditioned environment that eliminates the need for in vitro cell pre-conditioning while ensuring cell survival and function upon implantation
Solution Approach 2:
The biodegradable scaffold acts as an intermediary carrier that protects dissociated islet cells during delivery and provides a temporary supportive structure that facilitates cell aggregation and survival in the hostile in vivo environment without requiring pre-conditioning of the cells themselves
2Reliability
If donor islets are used for transplantation, then the cell source is reliable, but the quantity of available islets is insufficient
Solution Approach 1:
Whole islets are enzymatically dissociated into individual cells or small clusters, which are then delivered via the scaffold. This segmentation increases the quantity of deliverable cell units from limited donor islets while the scaffold facilitates their reorganization into functional structures
Solution Approach 2:
The invention changes the physical state of islet delivery from intact whole islets to dissociated cells delivered within a scaffold matrix, altering the delivery parameters to enable use of limited donor material while maintaining therapeutic effectiveness
3Reliability
If cell aggregation is performed in vitro prior to implantation, then the reliability of cell function is improved, but the complexity of the procedure and time required increase
Solution Approach 1:
The scaffold is designed to enable cells to self-organize and aggregate in situ after implantation through its microporous structure and bioactive cues, eliminating the need for complex in vitro aggregation procedures while achieving reliable cell function
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
The MAP scaffold supports the survival and function of dissociated islet cells both in vitro and in vivo, offering a promising treatment for Type 1 diabetes by mimicking native islet structure and facilitating cell-cell signaling.
Implementation Method 1
microporous annealed particle (MAP) scaffold
Implementation Method 2
microporous annealed particle (MAP) scaffold
Data Source
AI summary
Provided are compositions that include single cell suspensions of pancreatic islet cells, pancreatic islet-like cells derived from iPS cells, or combinations thereof, wherein the cells are present within a MAP scaffold and/or are encapsulated by MAPs. In some embodiments, the MAP scaffold and/the MAPs have a polymer backbone that includes poly(ethyleneglycol) (PEG), hyaluronic acid, polyacrylamide, polymethacrylate, alginate, collagen, or any combination thereof. Also provided are methods for using the presently disclosed compositions for treating Type 1 diabetes, for example by administering to a subject with Type 1 diabetes such a composition via a route and in an amount effective for treating the Type 1 diabetes in the subject. In some embodiments, the administering includes injecting the composition into a kidney capsule, subcutaneously, intraperitoneally, into adipose tissue, intramuscularly, intrahepatically, and/or intrapancreatically into the subject.