Biological response in photopolymer additive manufacturing: a review of formulation chemistry, workflow variables and qualification constraints in dental and biomedical applications

Abstract

Photopolymer vat photopolymerisation has expanded from prototyping into manufacturing and research workflows for dental and biomedical devices, including direct-printed clear orthodontic aligners, denture bases, surgical guides and research platforms. The regulatory environment has evolved in parallel through EU Medical Device Regulation 2017/745, revisions within the ISO 10993 series, and increased regulatory scrutiny of photopolymer constituents such as diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO). Against this backdrop, the term biocompatible resin continues to be used in ways that can conflate properties of a liquid formulation with the biological response of the cured printed device. The biological response of a printed device is not defined by formulation alone; it emerges from the interaction between formulation chemistry, photopolymerisation, post-processing, ageing under intended-use conditions and the chemical and mechanical environment of the device in service. This review examines the hypothesis that biocompatibility in photopolymer additive manufacturing is more appropriately treated as an outcome of interacting engineering layers — formulation design, workflow control, extraction qualification and temporal stability — than as a property of the raw material. The hypothesis is examined against the peer-reviewed evidence base on residual species characterisation, postcure degree of conversion, photoinitiator substitution, cytotoxicity assessment, hydrolytic and salivary stability and clinical performance of additively manufactured dental and medical devices. Two broad formulation approaches currently observed in the field — oligomer-dominant systems with reduced low molecular-weight reactive fraction, and conventional monomer-based formulations with screened components and partial bio-derived content — are mapped against the application space, with the limitations of each approach made explicit. Standardised extractables methodology and longer-term clinical follow-up emerge as principal research priorities through 2030.