Jigsaw Puzzle-Designed Polyphenol-Macromolecular Supramolecular Networks for Noninvasive Therapy of Deep-Tissue Oral Disease
Bibliographic record
Abstract
Transmucosal delivery of macromolecular biopharmaceuticals is favored for being noninvasive and bypassing first-pass metabolism. The oral mucosa provides a convenient route for patient-self-applied drug delivery, but its tight junctions and enzymatic environment hinder drug penetration. Here, we present a noninvasive nanoplatform based on a jigsaw puzzle design, enabling the construction of polyphenol-macromolecule supramolecular networks within ionic liquid (PMIL). Experimental and calculational analyses confirm that leveraging the multiple noncovalent interaction capabilities of green tea polyphenol (epigallocatechin gallate, EGCG), various macromolecular biopharmaceuticals (plasmids, siRNA, proteins, and polypeptides) can be self-assembled into PMIL nanoarchitectures. In periodontitis models, PMIL-loaded teriparatide demonstrated an exceptional tissue penetration capability, simultaneously reducing inflammation and promoting bone regeneration. PMIL enriched commensal and probiotic microbes unrelated to periodontal pathogenesis. Mechanistically, PMIL might modulate PI3K-Akt signaling to simultaneously reduce inflammation and promote bone regeneration. Our ingestible, modular platform provides a noninvasive solution for oral diseases and could be adapted for other macromolecular therapies.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".