Biocompatibility of poly(lactic acid) (PLA) and PLA/poly(e-caprolactone) (PCL) blend implanted in horses

Author(s)

Júlia Ribeiro Garcia Carvalho

• Document type: Master's Dissertation
• Press: Jaboticabal. 2019-04-09.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Ciências Agrárias e Veterinárias. Jaboticabal
• Defense date: 2019-02-25
• Advisor: Guilherme de Camargo Ferraz

Abstract

Biomaterials are designed to interact with biological systems, which may be synthetic as metal, or natural as biopolymers. The development of new technologies from renewable sources is widely used in the different areas of knowledge due to the great concern with the preservation of the environment. In veterinary medicine, there is interest in the development of long-lasting drug formulations, with biopolymers being feasible alternatives to play the role of carrier, as well as their use as scaffolds for bone regeneration, sutures, screws, pins and plates for orthopedic surgeries. The objective of this study was to evaluate the biocompatibility of poly(lactic acid) (PLA) and PLA/poly(ε-caprolactone) (PCL) new blends implanted subcutaneously in horses. Six equine, 3 male and 3 female, cross-breed, aged between 10 and 18 years and mean weight of 405 kg ± 37 were used. The experiment was composed of four experimental groups: control group (C), negative implant group (IN), PLA group and PLA/PCL group, being that the last two were submitted to the implantation of pure PLA and the PLA/PCL blends, respectively. The horses were submitted to a surgical procedure for implantation of the biopolymers in the subcutaneous tissue, on the lateral side of the neck. The polymers remained implanted for 6 months, and evaluations were performed before, 6, 12, 24, 48, 72, 96, 120, 144, 168 h, 2, 3, 4, 5, 6, 7, 8, 16 and 24 weeks after implantation. The physical examination consisted of evaluation of heart rate (HR), respiratory rate (RR), body temperature (BT), intestinal motility (IM), degree of hydration (DH), apparent mucosal coloration (AMC), and capillary filling time (CFT). The plasma fibrinogen concentration (PF) was determined. Infrared thermography (IRT) was used to determine the inflammatory response. The nociceptive response was evaluated by von Frey filaments (VFF). Ultrasound examination (US) was performed to evaluate the local responses to the presence of the material, in addition to the echogenicity of the polymers. At the end of the implantation period, the biomaterials were removed by means of cutaneous biopsy for histopathological analysis, using hematoxylin-eosin (HE) and picrosirius-hematoxylin (PSH) staining. Scanning electron microscopy (SEM) was performed to evaluate the structure and biodegradation of the material. Variance analysis was applied for repeated measurements followed by the Tukey test. The non-parametric Mann-Whitney test was used to evaluate the histopathological variables. All analyzes were performed with p <0.05. There was no change of clinical importance in the intra and intergroup comparisons for HR, RR, BT, IM, DH, AMC, CFT and PF. The IRT showed transient elevation of the cutaneous temperature (CT) of the implanted groups (PLA and PLA/PCL). Between 24 and 72 h after implantation, there was an increase in CT of the implanted groups (PLA and PLA/PCL) when compared to the IN and C groups. Nociceptive evaluation showed a decrease in the mechanical nociceptive threshold (MNT) of the implanted groups (PLA and PLA/PCL) and the IN group, in relation to group C, between 6 and 120 h after the procedure. There was a decrease in the MNT of the implanted groups in relation to the IN group 48 h after implantation. In the US, it was possible to observe greater edema in the implanted groups and in the IN group, in relation to the group C, between 6 and 168 h after the procedure. Between 48 and 96 h, the implanted groups had a higher degree of edema than the IN group. In addition, it was possible to show loss of echogenicity of the polymers, which started in the 5th week for the PLA group, and in the 6th week for the PLA/PCL group. In HE, it was possible to observe the formation of a granulomatous inflammatory reaction type foreign body, with no difference between the two types of polymers. In PSH, greater aggregation and compactness of the collagen fibers of the layer surrounding the polymer for the PLA group was observed. In the SEM it was possible to observe that the biomaterials (PLA and PCL/PLA) were in the process of biodegradation. It is concluded that both pure PLA and PLA/PCL blends are biocompatible and biodegradable with potential use in equine medicine. (AU)

• FAPESP's process: 17/10959-4 - Applicability of biopolymers implanted in horses
• Grantee: Júlia Ribeiro Garcia de Carvalho
• Support Opportunities: Scholarships in Brazil - Master