Biocompatibility assessment of encapsulation materials for micro LED biomedical applications: in vivo and in vitro studies

Abstract

The integration of Micro Light-Emitting Diodes (µLEDs) into biomedical systems holds significant promise for applications such as optogenetics, neural stimulation, and implantable biosensing. A critical challenge in realizing the clinical translation of such devices lies in ensuring the long-term biocompatibility of their encapsulation materials. In this study, we systematically evaluated the short-term (4-week) biocompatibility of three candidate encapsulation materials—Polydimethylsiloxane (PDMS), Ecoflex, and Kapton—and their respective µLEDs composites through a combination of in vitro and in vivo assays. In vitro cytotoxicity was assessed using direct contact morphology analysis, MTS mitochondrial activity assay, and Annexin-V/Propidium Iodide(PI)-based flow cytometry on L-929 fibroblasts. All materials demonstrated minimal cytotoxicity and apoptosis, with cell viability exceeding 90% and apoptotic indices remaining below 2.1%, meeting ISO 10993-5 criteria. Additionally, arsenic elution testing via inductively coupled plasma-mass spectrometry (ICP-MS) revealed concentrations far below toxicological thresholds, with Ecoflex and Kapton exhibiting undetectable levels. For in vivo evaluation, the materials were subcutaneously implanted into Sprague–Dawley rats. Histological analysis (Hematoxylin and eosin staining) conducted after 4weeks revealed no signs of necrosis or severe inflammatory response. Semiquantitative scoring indicated low fibrosis, inflammatory cell infiltration, and angiogenesis, with all materials falling within acceptable biocompatibility ranges. Collectively, these findings confirm that PDMS, Ecoflex, and Kapton, both as standalone films and in LED-integrated forms, exhibit excellent biocompatibility in short-term implantation models. This work provides a comparative foundation for selecting safe encapsulation materials in the development of implantable µLEDs bioelectronic systems and underscores the importance of multi-dimensional evaluation frameworks in preclinical safety assessment. © 2025 Elsevier B.V., All rights reserved.