{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T16:59:12Z","timestamp":1777913952360,"version":"3.51.4"},"reference-count":41,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2015,8,21]],"date-time":"2015-08-21T00:00:00Z","timestamp":1440115200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:p>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\u2122 devices (termed \u201ctest device\u201d). The test devices are made from a copolymer of poly-l-lactide-co-\u220a-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.<\/jats:p>","DOI":"10.1177\/0192623315600275","type":"journal-article","created":{"date-parts":[[2015,8,21]],"date-time":"2015-08-21T21:00:46Z","timestamp":1440190846000},"page":"1127-1140","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":53,"title":["Long-term Local and Systemic Safety of Poly(\n                    <scp>l<\/scp>\n                    -lactide-co-epsilon-caprolactone) after Subcutaneous and Intra-articular Implantation in Rats"],"prefix":"10.1177","volume":"43","author":[{"given":"Yuval","family":"Ramot","sequence":"first","affiliation":[{"name":"Hadassah\u2014Hebrew University Medical Center, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abraham","family":"Nyska","sequence":"additional","affiliation":[{"name":"Tel Aviv University and Consultant in Toxicologic Pathology, Timrat, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elana","family":"Markovitz","sequence":"additional","affiliation":[{"name":"Ortho-Space Ltd., Caesarea, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Assaf","family":"Dekel","sequence":"additional","affiliation":[{"name":"Ortho-Space Ltd., Caesarea, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy","family":"Klaiman","sequence":"additional","affiliation":[{"name":"Harlan Biotech Israel Ltd., Rehovot, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moran Haim","family":"Zada","sequence":"additional","affiliation":[{"name":"Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abraham J.","family":"Domb","sequence":"additional","affiliation":[{"name":"Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Ein Kerem, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert R.","family":"Maronpot","sequence":"additional","affiliation":[{"name":"Maronpot Consulting LLC, Raleigh, North Carolina, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2015,8,21]]},"reference":[{"key":"bibr1-0192623315600275","doi-asserted-by":"publisher","DOI":"10.1615\/JLongTermEffMedImplants.v21.i2.10"},{"key":"bibr2-0192623315600275","doi-asserted-by":"publisher","DOI":"10.5312\/wjo.v5.i5.557"},{"key":"bibr3-0192623315600275","doi-asserted-by":"publisher","DOI":"10.5435\/00124635-201402000-00002"},{"key":"bibr4-0192623315600275","doi-asserted-by":"publisher","DOI":"10.1016\/j.arthro.2013.06.014"},{"key":"bibr5-0192623315600275","first-page":"205","volume-title":"Banbury Report 25: Nongenotoxic Mechanisms in Carcinogenesis","author":"Brand K. 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