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.
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Buffer systems, artificial saliva, and selected saliva/serum samples show that PDA-based biosensing platforms can achieve improved biomolecule immobilization, signal transduction, fluorescence/electrochemical/SERS detection, and salivary biomarker analysis.
“Buffer systems, artificial saliva, and selected saliva/serum samples show improved biomolecule immobilization, signal transduction, fluorescence/electrochemical/SERS detection, and salivary biomarker analysis.”
From Polydopamine-Based Biomaterials in Oral Medicine: Applications, Mechanisms, and Translational Challenges (2026) · cites this paper as [20]
Data from a New Zealand rabbit tibial implantation model demonstrated favorable host responses to PDA-modified titanium alloy screws.
“With respect to in vivo tissue compatibility, data from a New Zealand rabbit tibial implantation model demonstrated favorable host responses to PDA-modified titanium alloy screws.”
From Polydopamine-Based Biomaterials in Oral Medicine: Applications, Mechanisms, and Translational Challenges (2026) · cites this paper as [20]
Immunohistochemical analysis showed that the expression of inflammatory markers CD68 and CD3 peaked at approximately 2 weeks and subsequently declined, while the macrophage M1/M2 ratio decreased from 2.1 to 0.6.
“Immunohistochemical analysis showed that the expression of inflammatory markers CD68 and CD3 peaked at approximately 2 weeks and subsequently declined, while the macrophage M1/M2 ratio decreased from 2.1 to 0.6.”
From Polydopamine-Based Biomaterials in Oral Medicine: Applications, Mechanisms, and Translational Challenges (2026) · cites this paper as [20]
Histological analysis at 4, 12, and 26 weeks post-implantation revealed only mild, localized mononuclear cell infiltration on hematoxylin and eosin staining, without the formation of thick fibrous capsules (<50 μm).
“Histological analysis at 4, 12, and 26 weeks post-implantation revealed only mild, localized mononuclear cell infiltration on hematoxylin and eosin staining, without the formation of thick fibrous capsules (<50 µm).”
From Polydopamine-Based Biomaterials in Oral Medicine: Applications, Mechanisms, and Translational Challenges (2026) · cites this paper as [20]
Cited by
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Ramot, Y., Rotkopf, S., Gabai, R. M., Zorde Khvalevsky, E., Muravnik, S., Marzoli, G. A., Domb, A. J., Shemi, A., & Nyska, A. (2016) · Toxicologic Pathology · doi:10.1177/0192623316645860 · Cited by 64 · see citing works
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Paiva, J. C. C., Oliveira, L., Vaz, M. F., & Costa-de-Oliveira, S. (2022) · Bioengineering · doi:10.3390/bioengineering9080409 · Cited by 53 · see citing works
Haim Zada, M., Kumar, A., Elmalak, O., Markovitz, E., Icekson, R., & Domb, A. J. (2020) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2019.118870 · Cited by 33 · see citing works
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Bachtiar, E. O., Ritter, V. C., & Gall, K. (2021) · Journal of the Mechanical Behavior of Biomedical Materials · doi:10.1016/j.jmbbm.2021.104650 · Cited by 27 · see citing works
Yang, Z., Song, W., Lv, L., Zhai, S., Liu, Y., Cui, H., Li, X., Gao, F., & Chu, S. (2026) · International Journal of Nanomedicine · doi:10.2147/ijn.s611922
“1,20,106 Taken together, existing evidence supports the conclusion that PDA-based materials exhibit favorable cytocompatibility and tissue tolerance.”
- Authors
- Ramot, Y., Nyska, A., Markovitz, E., Dekel, A., Klaiman, G., Zada, M. H., Domb, A. J., & Maronpot, R. R.
- Affiliations
- Hadassah Medical Center (IL)
- Tel Aviv University (IL)
- Ortho-Space Ltd., Caesarea, Israel
- Harlan Biotech Israel Ltd., Rehovot, Israel
- Hebrew University of Jerusalem (IL)
- Maronpot Consulting LLC, Raleigh, North Carolina, USA
- Corresponding author
- Nyska, Abraham
- Venue
- Toxicologic Pathology
- Publisher
- SAGE Publications
- Published
- 2015-08-21
- Volume
- 43
- Issue
- 8
- Pages
- 1127-1140
- ISSN
- 0192-6233 (ISSN-L)
- 1533-1601
- OpenAlex
- W2147897282
- Cited by
- 55
- References
- 0
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 2 · 2023: 8 · 2022: 3 · 2021: 6 · 2020: 10 · 2019: 7 · 2018: 4 · 2017: 1 · 2016: 6
- FWCI
- 1.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicologic Pathology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › biodegradable polymer synthesis and properties
- Health Sciences › Medicine › Surgery › Orthopaedic implants and arthroplasty
- Health Sciences › Medicine › Surgery › Surgical Sutures and Adhesives
- Keywords
- poly(L-lactide-co-ε-caprolactone), biodegradable polymers, biocompatibility, biodegradability, systemic toxicity, subcutaneous implantation, rotator cuff tear, fibrosarcoma, orthopedic implants
- MeSH terms
- Animals, Biocompatible Materials, Injections, Intra-Articular, Injections, Subcutaneous, Male, Materials Testing, Polyesters, Rotator Cuff, Rats, Sprague-Dawley, Prostheses and Implants, Subcutaneous Tissue, Rats
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