307.4: Subcutaneous Bioabsorption of Nanofibrous Scaffolds Influence the Engraftment and Function of Neonatal Porcine Islets Xenografts in Mice
Bibliographic record
Abstract
Dr. Korbutt and Dr. Pepper Introduction: The subcutaneous space is currently being pursued as an alternative transplant site for human pancreatic islets, stem cell and xenogeneic derived-islets, due to its retrievability, minimally invasiveness, accommodation of large transplant volumes, and potential for monitoring graft function. However, transplantation of islets into an unmodified subcutaneous niche fails to reverse diabetes due to a lack of adequate blood supply. Biomaterial nanofibrous scaffolds can be functionalized to enhance the host tissues integration, provide a platform for the delivery of pro-engraftment growth factors, and immunomodulatory agents. Method: Herein, we utilize poly (ε-caprolactone) (PCL) and poly (lactic-co-glycolic acid) (PLGA) polymers to make nanofibrous scaffolds and functionalized with bioactive peptides, to prime the subcutaneous space into a more suitable environment. We implanted the nylon catheter (2 cm length, 6 French diameter) (deviceless space, DL), and nanofibrous scaffolds (scaffold was wrapped around the nylon catheter) such as PCL, PCL+RGD+VEGF (PCL+R+V), PCL+RGD+Laminin (PCL+R+L), PLGA and PLGA+Gelatin (PLGA+G) into the subcutaneous space of immunodeficient B6.129S7-Rag1tm1Mom/J mice for four weeks to create a prevascularized space. After 4 weeks, DL and scaffolds implanted mice and those intended for kidney capsule (KC) implantation were rendered diabetic by intraperitoneal injection of 180 mg/kg streptozotocin. Subsequently, neonatal porcine islets (3000 NPI) were transplanted under the KC or within the subcutaneous DL and scaffolds. Graft function was evaluated by monitoring non-fasting blood glucose, stimulated porcine insulin measurement, intraperitoneal glucose tolerance test, and histochemical analysis. Results: Our preliminary scaffolds implantation (no cells) study demonstrates that PCL, PCL+R+V and PCL+R+L scaffolds did not absorb and partially integrated with the host tissues (PCL based scaffolds remain intact at the implanted site) whereas PLGA and PLGA+G scaffolds were completely absorbed and integrated with the host tissues (no remnants of PLGA based scaffolds at the implanted site), and we also observed that there were numerous blood vessels innervated in and around these scaffolds. Compared with peptide functionalized PCL scaffolds, PLGA and PLGA+G fibrous scaffolds with NPI resulted in 86% and 100% euglycemia (*p< 0.05, **p<0.01 respectively), superior glucose clearance (*p<0.05) and greater stimulated porcine insulin secretion (*p<0.05). Moreover, PLGA and PLGA+G scaffolds exhibited comparable graft functions with the positive controls (DL and KC)(p>0.05). Conclusion: Our study demonstrates that PLGA based fibrous scaffolds facilitates the engraftment and function of NPIs in the subcutaneous space of diabetic mice. These collective data emphasize the support of biomaterial implants on cellular graft function in the subcutaneous space for clinical islet xenotransplant applications in a near future.
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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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".