title: Long-term Local and Systemic Safety of Poly(L-lactide-co-epsilon-caprolactone) after Subcutaneous and Intra-articular Implantation in Rats.
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-∊-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.
authors: Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Yuval
authors: Y
authors: Ramot
authors: Tel Aviv University and Consultant in Toxicologic Pathology, Timrat, Israel anyska@bezeqint.net.
authors: Abraham
authors: A
authors: Nyska
authors: Ortho-Space Ltd., Caesarea, Israel.
authors: Elana
authors: E
authors: Markovitz
authors: Ortho-Space Ltd., Caesarea, Israel.
authors: Assaf
authors: A
authors: Dekel
authors: Harlan Biotech Israel Ltd., Rehovot, Israel.
authors: Guy
authors: G
authors: Klaiman
authors: Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem, Jerusalem, Israel.
authors: Moran Haim
authors: MH
authors: Zada
authors: Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem, Jerusalem, Israel.
authors: Abraham J
authors: AJ
authors: Domb
authors: Maronpot Consulting LLC, Raleigh, North Carolina, USA.
authors: Robert R
authors: RR
authors: Maronpot
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D007270:Injections, Intra-Articular; D007279:Injections, Subcutaneous; D008297:Male; D008422:Materials Testing; D011091:Polyesters / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D019736:Prostheses and Implants; D051381:Rats; D017207:Rats, Sprague-Dawley; D017006:Rotator Cuff / Q000187:drug effects*; D040521:Subcutaneous Tissue / Q000187:drug effects*
chemical_list: D001672:Biocompatible Materials; D011091:Polyesters; C062968:lactide-caprolactone copolymer
keywords: biocompatibility; biodegradability; biodegradable materials; rotator cuff syndrome; safety studies