Background: Phthalic acid esters are widely used to improve the plasticity of PVC in medical devices (MD). The most famous plasticizer is DEHP, whose use in medical devices has been contested by the European authorities since 2008. Several alternative plasticizers are being considered to replace DEHP, such as DEHT, TOTM, DINP or DINCH, but they are also released from the PVC throughout their life cycle and are metabolized in the same way as DEHP. Objectives: Our study focuses on the in vitro cytotoxicity of two alternative plasticizers (DINCH and DINP) contained in certain medical devices. They are likely to migrate and be transformed in vivo into the primary and secondary metabolites by a metabolism similar to that of DEHP. This preliminary study is the first to assess the in vitro cytotoxicity of oxidized metabolites of DINCH and DINP based on the EN ISO 10-993-5 standards documents. Methods: We have studied the complete multi-step organic synthesis of secondary metabolites of DINP and DINCH and have performed cytotoxicity tests on L929 murine cells according to the ISO-EN ISO 10993-5 standard design for the biocompatibility of a MD. The tested concentrations of obtained metabolites (0.01, 0.05 and 0.1 mg/mL) covered the range likely to be found for DEHP (total metabolism) in biological fluids coming into direct contact Highlights  7-oxo-MMeOCH and 5-oxo-MEHP induced no action on cell proliferation at 0.1 mg/mL  Among secondary metabolites of DEHP, 5-oxo-MEHP induced an action on L929  Among secondary metabolites of MMeOCH, 7-oxo-MMeOCH induced an action on L929  Secondary metabolites of MMeOCH are less toxic than MMeOCH  Secondary metabolites of MMeOP are not toxic like MMeOCH

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Human adipose-derived stromal cells (hASCs) are widely known for their immunomodulatory and anti-inflammatory properties. This study proposes a method to protect cells during and after their injection by encapsulation in a hydrogel using a droplet millifluidics technique. A biocompatible, self-hardening biomaterial composed of silanized-hydroxypropylmethylcellulose (Si-HPMC) hydrogel was used and dispersed in an oil continuous phase. Spherical particles with a mean diameter of 200 μm could be obtained in a reproducible manner. The viability of the encapsulated hASCs in the Si-HPMC particles was 70% after 14 days in vitro, confirming that the Si-HPMC particles supported the diffusion of nutrients, vitamins, and glucose essential for survival of the encapsulated hASCs. The combination of droplet millifluidics and biomaterials is therefore a very promising method for the development of new cellular microenvironments, with the potential for applications in biomedical engineering.

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