**1. Introduction**

Biodegradable materials have been widely studied for medical applications during the last decades due to their numerous benefits over non-biodegradable materials. Importantly, since these materials disappear after degradation, the implants do not need to be removed. Furthermore, implants prepared using biodegradable polymers can prevent recurrences in the event of fractures, as they can be designed to degrade at a rate that will slowly transfer the load to the healing bone, thus allowing for adequate healing [1,2]. However, these materials also have some technical limitations that make them difficult to process and use as a final product, such as limited control over physicochemical properties, because of the intrinsic raw material variability and difficulties in adjusting degradation rates [1,3].

Poly(lactic acid) (PLA) is one of the most widely used biopolymers and has the potential to be used as an alternative to high-cost, non-biodegradable biocompatible materials. PLA holds promising applications in several areas, particularly in packaging, agricultural

**Citation:** Carvalho, J.R.G.; Conde, G.; Antonioli, M.L.; Santana, C.H.; Littiere, T.O.; Dias, P.P.; Chinelatto, M.A.; Canola, P.A.; Zara, F.J.; Ferraz, G.C. Long-Term Evaluation of Poly(lactic acid) (PLA) Implants in a Horse: An Experimental Pilot Study. *Molecules* **2021**, *26*, 7224. https:// doi.org/10.3390/molecules26237224

Academic Editors: Marek Brzezi ´nski and Małgorzata Ba´sko

Received: 16 October 2021 Accepted: 24 November 2021 Published: 29 November 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

products, disposable materials, and the biomedical industry [4,5]. Among its advantages we list its biodegradability, renewability and low environmental impact when discarded. In addition, PLA has good biological safety, mechanical resistance, and processability profiles [6,7]. In the biomedical area, PLA has been used as a degradable suture, bone fixation device, material for surgical implants, drug delivery systems, and scaffolds for human and rodent tissue engineering applications [1,6,8,9].

Therefore, the medical application of PLA in horses can be an exciting opportunity for the experimental development of new biomaterials, as this species undergoes a fast and excessive healing process, which tends to follow abnormal repair reactions such as the formation of exuberant granulation tissue [10,11]. Moreover, with a global herd totaling about 61 million heads and a relevant world market, this animal species is part of the cattle production chain, utilized as a companion animal or in numerous sports, with emphasis on Olympic sports [12,13]. Thus, PLA may be an interesting alternative with potential application in equine medicine.

In the equine species, therapeutic polymer implants can mimic tissues, promote cell proliferation, and tissue reconstitution, forming a conjunctive capsule. Moreover, they can be combined with drugs for systemic or local action. However, polymer implants must be biocompatible and bioabsorbable [4,8]. There are few studies on the use of polymer implants in horses, with most of them involving their use to repair bone fractures [13–17]. Therefore, polymeric materials represent potential alternatives to the use of autologous and heterologous grafts, which have been limited to fracture correction in equine medicine [13,15]. Furthermore, biomaterials have been used for the treatment of joint damage [18–20] and drug delivery [21]. Among these studies, only one used PLA for internal fixation of fractures of horses' proximal sesamoid bone. PLA proved superior to metallic implants because the animals presented a lower degree of lameness and better-quality bone remodeling [14].

Our research group recently evaluated the biocompatibility and biodegradability of PLA and a polymer blend based on PLA and poly(ε-caprolactone) (PCL) compatibilized with a copolymer derived from ε-caprolactone and tetrahydrofuran, which was implanted subcutaneously in horses. However, the materials were only implanted for 24 weeks [22]. Herein, we expand these findings by evaluating the biocompatibility and biodegradability of six PLA implants in a horse up to 57 weeks. Such long-term evaluation of polymer implants has not been performed previously in horses. Our data shows that the PLA implants do not provoke toxic reactions and can be applied safely in vivo for extended times in the equine species.
