Research Article: An in vitro and in vivo study on the properties of hollow polycaprolactone cell-delivery particles

Date Published: July 3, 2018

Publisher: Public Library of Science

Author(s): Barend Andre Stander, Fiona A. van Vollenstee, Karlien Kallmeyer, Marnie Potgieter, Annie Joubert, Andri Swanepoel, Lara Kotze, Sean Moolman, Michael S. Pepper, Arun Rishi.


The field of dermal fillers is evolving rapidly and numerous products are currently on the market. Biodegradable polymers such as polycaprolactone (PCL) have been found to be compatible with several body tissues, and this makes them an ideal material for dermal filling purposes. Hollow PCL spheres were developed by the Council for Scientific and Industrial Research (CSIR) to serve both as an anchor point and a “tissue harbour” for cells. Particles were tested for cytotoxicity and cell adherence using mouse embryo fibroblasts (MEF). MEFs adhered to the particles and no significant toxic effects were observed based on morphology, cell growth, cell viability and cell cycle analysis, suggesting that the particles are suitable candidates for cell delivery systems in an in vivo setting. The objective of providing a “tissue harbour” was however not realized, as cells did not preferentially migrate into the ported particles. In vivo studies were conducted in BALB/c mice into whom particles were introduced at the level of the hypodermis. Mice injected with PCL particles (ported and non-ported; with or without MEFs) showed evidence of local inflammation and increased adipogenesis at the site of injection, as well as a systemic inflammatory response. These effects were also observed in mice that received apparently inert (polystyrene) particles. Ported PCL particles can therefore act as a cell delivery system and through their ability to induce adipogenesis, may also serve as a dermal bulking agent.

Partial Text

Dermal filling is a popular method for addressing trauma, disease and age related contour defects of the skin [1, 2]. The size of the USA dermal filler market in 2016 was estimated at 2.6 million doses per annum and increased by 2% from 2015. This market consists of a range of injectable liquids and suspended solids, including hyaluronic acid, calcium hydroxyapatite (Radiesse®) and polymethyl-methacrylate microspheres (Artefill®) [3]. In 2014, the dermal filler portfolio available in Europe was estimated to be exponentially larger than that in the USA [4].

Apart from its tissue-filling requirement, the ideal tissue filler needs to have minimal adverse effects. Thus, the most important aspect when dealing with tissue fillers is their safety and biocompatibility. Biocompatibility can be achieved with careful design, concentrating on chemical composition, surface structure, surface charge and particle size [29]. Cell-material interactions can be modulated. When an inert surface is designed, it does not allow for adsorption of proteins and adhesion of cells [30]. It aims to prevent immune response activation and any interaction between the material and the surrounding environment. Such a design is biocompatible; however, it applies to more permanent synthetic replacement of damaged tissues. For co-transplantation of cells with cell delivery vehicles, materials promoting cell attachment, migration, proliferation, differentiation, long-term viability and cell functioning are more appropriate. This kind of delivery vehicle aims at creating “hybrid bioartificial organs” for tissue engineering [30].




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