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Biocompatibility and biodegradation of poly(lactic acid) (PLA) and an immiscible PLA/poly(ε-caprolactone) (PCL) blend compatibilized by poly(ε-caprolactone-b-tetrahydrofuran) implanted in horses

Abstract

This paper focuses on the biocompatibility and biodegradation of PLA and a recently developed PLA/PCL blend containing an in vitro nontoxic compatibilizer based on a low-molecular-weight triblock copolymer derived from ε-caprolactone and tetrahydrofuran. The polymers were implanted subcutaneously in the lateral surface of the neck of horses. Physical examination, plasma fibrinogen (PF) analysis, infrared thermography (IT), mechanical nociceptive threshold (MNT) analysis, and ultrasonography were performed. After 24 weeks, the biomaterials were removed for histochemical analysis using hematoxylin-eosin (HE) and picrosirius-hematoxylin (PSH) staining. Scanning electron microscopy (SEM) was employed to determine changes in the surface morphology of the PLA and PLA/PCL blend. There were no clinical or PF changes. IT indicated a transient increase in cutaneous temperature (CT), while MNT decreased after the procedure in both the implanted groups. Ultrasonography revealed edema after the procedure and the loss of echogenicity of the polymers after implantation. Both polymers elicited a foreign body response under microscopic analysis. The PSH technique revealed a fibrotic reaction with collagen deposition around the polymers. SEM showed surface roughness, suggesting a biodegradation process. In conclusion, PLA and the PLA/PCL blend were biocompatible and biodegradable, with potential for use in equine medicine.

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Acknowledgements

This work was funded by The São Paulo Research Foundation (FAPESP, process no. 2017/10959-4 and process no. 2015/26738-1) and the National Council for Scientific and Technological Development (CNPq, process no. 132700/2017-4). Also, this study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001. We thank Professor Áureo Evangelista Santana and the Clinical Pathology Laboratory of the Veterinary Hospital (FCAV/UNESP) for their excellent technical assistance, and Professor Fernando José Zara for his collaboration in conducting the scanning electron microscopy analysis. We also thank the Graduate Course Program in Veterinary Medicine (FCAV/UNESP) and the Department of Animal Morphology and Physiology (FCAV/UNESP) for the academic support. This work is part of the requirements to obtain a Ph.D. degree by Júlia Ribeiro Garcia de Carvalho in the Graduate Course in Veterinary Medicine (FCAV/UNESP), SP, Brazil.

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GCF and JRGC designed the study. GCF supervised the study. PPD and MAC developed and supplied the polymers used in the study, analyzed data concerning polymer biodegradation and wrote these results in the paper. JRGC, GC, and MLA performed the experiment and collected the data. JRGC, GC, ROV, SRT, and GCF analyzed the data and interpreted the results. GTP and GCF performed the statistical analyses. JRGC, GC, MLA, and GCF drafted the paper. ROV, SRT, PAC, PPD, MAC and GCF aided in planning and provided critical readings of the paper. JRGC and GCF wrote and finalized the article. All authors are aware of the content and have read and edited the paper.

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Correspondence to Guilherme C. Ferraz.

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The study followed the Ethical Principles in Animal Experimentation adopted by the Brazilian College of Animal Experimentation and was approved and supervised by the institutional animal use and care committee (006548/17).

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Carvalho, J.R.G., Conde, G., Antonioli, M.L. et al. Biocompatibility and biodegradation of poly(lactic acid) (PLA) and an immiscible PLA/poly(ε-caprolactone) (PCL) blend compatibilized by poly(ε-caprolactone-b-tetrahydrofuran) implanted in horses. Polym J 52, 629–643 (2020). https://doi.org/10.1038/s41428-020-0308-y

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