Interspecies Differences in Reaction to a Biodegradable Subcutaneous Tissue Filler

Abstract

Soft tissue filler products have become very popular in recent years, with ever-increasing medical and aesthetic indications. While generally considered safe, the number of reported complications with tissue fillers is growing. Nevertheless, there is no specific animal model that is considered as the gold standard for assessing safety or efficacy of tissue fillers, and there are very little data on interspecies differences in reaction to these products. Here, we report on interspecies differences in reaction to a subcutaneous injectable co-polyester, composed of castor oil and citric acid. Comparison of the histopathological local tissue changes following 1-month postimplantation, indicated that in rats the reaction consisted of cavities, surrounded by relatively thin fibrotic enveloping capsule. In contrast, an unexpected severe inflammatory granulomatous reaction was noticed in Sinclair minipigs. To our knowledge, this is the first report on significant interspecies differences in sensitivity to tissue fillers. It emphasizes the importance of using the appropriate animal model for performing preclinical biocompatibility assays for biodegradable polymers, tissue fillers, and implanted medical devices in general. It also makes the Sinclair minipig subject for scrutiny as an animal model in future biocompatibility studies.

Biocompatibility, biodegradation and biomedical applications of poly(lactic acid)/poly(lactic-co-glycolic acid) micro and nanoparticles

“…It is worthy to mention that biocompatibility is not only the polymer's intrinsic property-dependent or particulate type-dependent, but also, biological environment-dependent and hence, intensity and length of specific polymer-tissue interactions can be varied greatly in different organs, tissues and species (Makadia and Siegel 2011;Ramot et al 2016Ramot et al , 2015. Thus, site of administration of PLA and PLGA based DDS greatly impacted foreign body responses.…”

Pathology of Bioabsorbable Implants in Preclinical Studies

“…This decrease in irritancy score as time progressed was due to the slower bioabsorption profile of the control implant, with early time points having a relatively benign appearance in the control group compared to the test group while later time points demonstrated active bioabsorption in both treatment groups. Ramot, Touitou, et al (2015) reported on interspecies differences in reaction to a subcutaneous injectable copolyester, composed of castor oil and citric acid. The test compound was intended for use as dermal filler and was tested for its tissue biocompatibility in rats and pigs.…”

The minipig as a new model for the evaluation of doxorubicin‐induced chronic toxicity

“…Mouse models have also been used extensively (Shuai et al ., ; Desai et al ., ), however, while providing important insights into doxorubicin‐induced toxicity and possible interventions, there are several limitations that question the clinical relevance of the mouse model to humans (Desai et al ., ). The minipig has emerged as a translational, non‐rodent animal model for safety assessment and regulatory toxicity studies (Nunoya et al ., ; Vezzali et al ., ; Ganderup et al ., ; Zhang et al ., ; Ramot et al ., ), and has been suggested to present a better profile in terms of the similarity to humans and utility to various type of studies (Bode et al ., ; van der Laan et al ., ). This is especially important when evaluating cardiovascular toxicity, based on the high similarity between cardiac anatomy and physiology between minipigs and humans (Stubhan et al ., ).…”