Long-term local and systemic safety of poly(l -lactide-co-epsilon-caprolactone) after subcutaneous and intra-articular implantation in rats

Yuval Ramot, Abraham Nyska, Elana Markovitz, Assaf Dekel, Guy Klaiman, Moran Haim Zada, Abraham J. Domb, Robert R. Maronpot

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

The use of biodegradable materials is gaining popularity in medicine, especially in orthopedic applications. However, preclinical evaluation of biodegradable materials can be challenging, since they are located in close contact with host tissues and might be implanted for a long period of time. Evaluation of these compounds requires biodegradability and biocompatibility studies and meticulous pathology examination. We describe 2 preclinical studies performed on Sprague-Dawley rats for 52 weeks, to evaluate clinical pathology, biocompatibility, biodegradability, and systemic toxicity after implantation of 2-layered films or saline-inflated balloon-shaped implants of downsized InSpace™ devices (termed 'test device'). The test devices are made from a copolymer of poly-l-lactide-co-âš-caprolactone in a 70:30 ratio, identical to the device used in humans, intended for the treatment of rotator cuff tears. Intra-articular film implantation and subcutaneous implantation of the downsized device showed favorable local and systemic tolerability. Although the implanted materials have no inherent toxic or tumorigenic properties, one animal developed a fibrosarcoma at the implantation site, an event that is associated with a rodent-predilection response where solid materials cause mesenchymal neoplasms. This effect is discussed in the context of biodegradable materials along with a detailed description of expected pathology for biodegradable materials in long-term rodent studies.

Original languageEnglish
Pages (from-to)1127-1140
Number of pages14
JournalToxicologic Pathology
Volume43
Issue number8
DOIs
StatePublished - 1 Dec 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 by The Author(s).

Keywords

  • biocompatibility
  • biodegradability
  • biodegradable materials
  • rotator cuff syndrome
  • safety studies

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