Titanium salts tested in reconstructed human skin with integrated <scp>MUTZ</scp>‐3‐derived Langerhans cells show an irritant rather than a sensitizing potential
Bibliographic record
Abstract
Abstract Background The nature of clinically related adverse reactions to titanium is still unknown. Objective To determine whether titanium salts have irritant or sensitizing potential in a reconstructed human skin (RHS) model with integrated Langerhans cells (LCs). Methods RHS‐LCs (ie, reconstructed epidermis) containing primary differentiated keratinocytes and CFSE+CD1a+‐LCs generated from the MUTZ‐3 cell line on a primary fibroblast‐populated collagen hydrogel (dermis) were topically exposed to titanium(IV) bis(ammonium lactato)dihydroxide (TiALH). LC migration and plasticity were determined. Results TiALH resulted in CFSE+CD1a+‐LC migration out of the epidermis. Neutralizing antibodies to CCL5 and CXCL12 showed that LC migration was CCL5 and not CXCL12 mediated. LCs accumulating within the dermis after TiALH exposure were CFSE+Lang+CD68+ which is characteristic of a phenotypic switch of MUTZ‐LC to a macrophage‐like cell. Furthermore, TiALH did not result in increased interleukin (IL)‐1β or CCR7 messenger RNA (mRNA) in the dermis, but did result in increased IL‐10 mRNA. In addition, monocultures of MUTZ‐LCs failed to increase LC maturation biomarkers CD83, CD86, and CXCL‐8 when exposed to noncytotoxic concentrations of four different titanium salts. Conclusion These results classify titanium salts as irritants rather than sensitizers and indicate that titanium implant‐related complaints could be due to localized irritant‐mediated inflammation arising from leachable agents rather than a titanium metal allergy.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".