Methacrylic Acid-Based Biomaterials for Subcutaneous Pancreatic Islet Transplantation
Bibliographic record
Abstract
Type 1 diabetes (T1D) is an autoimmune disease that results in the inability to control blood glucose levels, leading to hyperglycemia. Although currently managed by insulin injections, tighter regulation is required. An alternative treatment method is pancreatic islet transplantation. The subcutaneous space offers a promising site for islet transplantation as it is non-invasive and offers retrievability of the graft, however, this site requires external vascularization to support the metabolically demanding cells. Methacrylic acid (MAA) based biomaterials have proven to be an effective method for vascularizing the subcutaneous space and making it a suitable site for transplantation.Here we explore the use of MAA-based biomaterials for islet transplantation and evaluate its effect on the immune and oxygen environment of the subcutaneous space. We evaluated the ability of MAA-induced vascularization to support the viability of alginate-poly-l-lysine-alginate (APA) microencapsulated islets. Despite the lack of direct vessel integration, MAA was able to support microencapsulated islet function in the subcutaneous space resulting in a reversal of hyperglycemia in an immune compromised model. This offers a potential immune mitigation strategy for islet transplantation. To transition the MAA hydrogel to an allogeneic model, we also focused on how the immune cell niche is impacted. The delivery of MAA compared to PEG, resulted in an increased cellular response comprised primarily of neutrophils in an immune competent model. There was also a significant upregulation of Ifn-γ in Balb/c compared to SCID/bg with the delivery of MAA, pointing to a more pro-inflammatory cellular environment. The use of a neutrophil depleting antibody showed promise in addressing this acute response and promoting long-term engraftment of islets. We also explored the effect of MAA on the oxygen environment in the subcutaneous space. We highlighted the importance of hydrogel volume and cell density on islet engraftment and the reversal of hyperglycemia in a diabetic immune compromised mouse. Based on the Krogh Cylinder model which predicts oxygen tension within a cylindrical tissue, more vessels are required for hydrogel transplants of higher cell density to compensate for the increased oxygen demand. In this work we identified that a volume fraction of 0.005 is required for islet function based on vessel density and oxygen tension measurements. This offers a starting point for the scale up of the MAA hydrogel system: a larger hydrogel volume is required to support an increased islet dose in larger animals. Subcutaneous islet transplantation may offer a functional cure for Type 1 diabetes. In this work we demonstrate the potential and translatability of the MAA-based hydrogel as an islet delivery platform.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".