When Genes Meet Gels: Computational Immunogenetics of Dermal Fillers and Stratified Risk of Immune and Fibrotic Reactions across Compositions and Genotypes.

backgroundDelayed inflammatory and fibrotic reactions to dermal fillers remain unpredictable, reflecting complex interactions between product composition and host genetics.

objectiveTo develop and validate a computational framework integrating filler physicochemical attributes with simulated genetic variation to estimate relative immunologic and fibrotic risk across commercially available products.

methodsTwenty-six fillers were analysed using a hierarchical Bayesian model combining rheologic, structural, and compositional parameters with genotype-specific modifiers in AesthetiSIM™, a reproducible Docker-based environment. Posterior distributions were derived for biostimulatory, immunogenic, and fibrotic indices, and composite scores were normalized to the [0-1] interval. Sensitivity analyses included exposure-adjusted validation, leave-one-product-out cross-validation, and variance decomposition to assess robustness.

resultsRisk scores formed a continuous spectrum. Profhilo, Juvéderm Volite, Voluma XC, and Evolysse™ SMOOTH occupied the lowest strata (mean < 0.15), whereas Sculptra, Radiesse, and HArmonyCa showed the highest (mean > 0.75). The scores quantify relative risk gradients rather than absolute event probabilities. Cluster and heatmap analyses revealed distinct mechanistic classes consistent with known material properties.

conclusionDermal filler safety exists on a graded continuum determined jointly by composition and genetic susceptibility. This integrative, reproducible model provides an evidence-organized framework for personalized product selection and informed patient counselling in precision aesthetic practice. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .