Carrier-Limited Release Risk in Electrospun Nanofibers for Regenerative Endodontics: Constraint Discovery from 25 Formulations

Abstract

Regenerative endodontics needs an intracanal carrier that keeps disinfecting across a dressing interval that clinicians schedule at one to four weeks, without harming the stem cells that rebuild the pulp. We ask what one completed 25-formulation electrospinning campaign of poly(vinylpyrrolidone) (PVP) fibers carrying metronidazole, ciprofloxacin, minocycline and Ca(OH)2 can decide, and use machine learning for constraint discovery and decision support rather than as a new predictor. After an audit against the source thesis, logistic regression predicts fine-fiber formation at 96% leave-one-out accuracy, but a one-threshold rule does as well, the gain over the 80% majority baseline is not significant (exact McNemar p = 0.125), and accuracy falls to 84% when mixture loading is encoded per component. Diameter models interpolate within formulation families (ridge MAE 193 nm, 95% CI 96 to 317 nm) and fail across them (R^2 < 0). Because the campaign never measured release, we assemble a same-drug, cross-carrier evidence table: 17 bounded metronidazole and ciprofloxacin observations from seven studies, with two-sided censoring. Water-soluble carriers (PVP, PVA) completed release within 80 h (PVP within 8 h); no water-insoluble monolithic carrier reached 90% within its observation window, releasing 1.5 to 50%; both within-study comparisons separate at matched loading; and blend, core-shell and thick-mat architectures released over 3 to 28 days. The PVP mats therefore carry a carrier-limited release risk, not a proven ceiling, and one dissolution experiment can confirm or overturn it. A censoring-aware screen keeps three necessarily and one possibly nondominated formulation, and fixed-budget replays show that uncertainty sampling finds failed formulations sooner, except the one it is confidently wrong about.