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 ªtissue harbourº 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 ªtissue harbourº 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 nonported;
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.
S1 File. Figure A: Chronic inflammation in the test animals over the trial period. Figure B:
Acute inflammation in the test animals over the trial period. Figure C: Tissue necrosis in the
test animals over the trial period. Figure D: Fibrosis in the test animals over the trial period.
Figure E: Granulomatous/foreign body response in the test animals over the trial period.
Figure F: Representative TEMs of skin biopsies of particles group (A) and particles+MEFs
group (B) in the in vivo experiment injecting particles+MEFs. Particles could be identified in
skin biopsies of both the particles and particles+MEFs groups. The aim of the TEM investigation
was to determine if any cells could be detected inside the particles. No cells were present
inside the particles in either group. These results reflect the conclusion that was made after the
light microscopy study, indicating that cells did not migrate into the ported PCL particles. Bar
in A = 5μm and in B = 10μm.
S2 File. In vitro and in vivo data. Table A: Groups of rats used in the biotoxicity trial. Table B:
Observations on mice in the in vivo experiment assessing the effect of ported PCL particles
and cells. Table C: Statistical comparisons preformed between the various white blood cell
types assessed from blood smears of experimental mice injected with ported PCL particles
with or without MEFs. Table D: Schedule of the in vivo experiment assessing the effect of
ported and non-ported PCL as well as polystyrene (PS) particles. Table E: Overview of the animals,
tests and procedures performed in the in vivo experiment assessing the effect of ported
and non-ported PCL as well as polystyrene (PS) particles in BALB/c mice.
S3 File. All data underlying the findings of the study.