**1. Introduction**

Periodontal disease is a chronic inflammatory condition caused by a highly pathogenic biofilm. If left untreated, it may result in irreversible destruction of the supporting periodontal tissues, which consists of the hard and soft tissues surrounding and supporting the teeth. In severe cases, reduced periodontal support can lead to tooth loss, requiring tissue bone augmentation and regeneration, followed by surgical procedures to restore the reconstitution of the complex structure of the tissue [1].

In clinical applications, various attempts have been made to repair the bone/periodontal apparatus over the last four decades. These include root surface conditioning, graft materials, non-resorbable membranes of polytetrafluoroethylene (e-PTFE), and bioceramic scaffolds [2]. However, the regeneration of defective or damaged bone/periodontal tissue has been challenging in reconstructive surgery. Furthermore, it is still considered a common cause of permanent functional loss and post-traumatic morbidity [3].

Hence, guiding the regeneration processes of the bone/periodontal apparatus's complex architecture still represents one of the most significant challenges in modern dentistry. From an anatomical and physiological perspective, the functional integration of composite scaffolds and/or polymeric matrices doped with nanoparticles that synchronously guide the tissue's regeneration is still demanding [4].

In recent years, scaffolds that combine a biodegradable polymers matrix, such as PCL, PLGA, or PLA doped with bioceramics (i.e., hydroxyapatite, TiO2, magnesium-calcium

**Citation:** Osorio-Arciniega, R.; García-Hipólito, M.; Alvarez-Fregoso, O.; Alvarez-Perez, M.A. Composite Fiber Spun Mat Synthesis and In Vitro Biocompatibility for Guide Tissue Engineering. *Molecules* **2021**, *26*, 7597. https://doi.org/10.3390/ molecules26247597

Academic Editors: Marek Brzezi ´nski, Małgorzata Ba´sko and Roberta Cassano

Received: 22 October 2021 Accepted: 10 December 2021 Published: 15 December 2021

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**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/).

silicate, β-Tricalcium phosphate, mineral trioxide aggregate, calcium phosphate) have received considerable attention as promising biomaterials with potential for next-generation bone tissue engineering scaffolds, since they provide peculiar bioactive signals to improve osteoconductivity and to enhance mesenchymal stem cells adhesion, migration, and differentiation [5–10]. In addition, among the different calcium ceramics used in the application in bone and periodontal surgery, there is also the use of zirconium oxide (ZrO2) due to its excellent physicochemical properties, its high chemical and dimensional stability, its low ionic and thermal conductivity, its excellent mechanical resistance, fracture toughness, its low cytotoxicity, and its biocompatibility response [11,12]. Moreover, the use of the thermoplastic aliphatic polyester as polylactic acid (PLA) in bone tissue engineering is because it has numerous interesting properties, including excellent mechanical properties, thermal stability, processability, and low environmental impact. However, its most important characteristic is that it is Food and Drug Administration (FDA) approved for the low toxicity and degradation products (H2O and CO2) that do not interfere with tissue healing. Indeed, the hydrolyzes of the constituent of PLA could be incorporated into the tricarboxylic acid cycle and excreted, making it a natural choice for biomedical applications [13,14].

Recently, the synthesis of polymeric nano- or microfibers with bioceramics via electrospinning has been widely applied in bone tissue engineering; due to its large surface/volume ratio, the process allows modification of their physical or chemical properties and enables precise control over the shapes and structures of the fibers, which is often reported in the literature [8,15–19]. Likewise, another versatile, low-cost, safe (does not employ high voltage), scalable, and versatile method that produces micro/nanoscale fibers from different synthetic and natural polymers is the air-jet spinning (AJS) method. This method utilizes a specialized spinning system nozzle, such as a commercial airbrush, a surface for collecting polymer fibers, and compressed gas through which the polymer solution and a pressurized gas are simultaneously ejected to form the fiber morphology, allowing the design of sheet-like platforms that could be applied in bone and tissue engineering [20–23]. Furthermore, poly(lactic acid) fiber scaffolds were successfully fabricated, and our in vitro biological response of mesenchymal stem cells showed that the polymer concentration and fiber size influenced the biocompatibility response. Furthermore, our results indicated that nanofibrous topography possesses the potential to enhance cell adhesion and proliferation and improve the cues to guide the fiber orientation by the cells; additionally, our in vivo studies showed that PLA fiber spun scaffolds are not cytotoxic in a Wistar rat model [24–26]. Moreover, our previous results, where we reported the synthesis of polymer composites composed of PLA/ZrO2 to attempt optimization of the fabrication by AJS, showed that composites have a fibrous morphology with a random distribution, with a diameter of fibers and mechanical properties depending on polymer and zirconia concentrations, suggesting that the PLA/ZrO2 composite may be used as a biomaterial [27]. Thus, we propose the preparation of a composite by using a polymer solution of 10% wt of PLA with 0.1 and 0.5 g of ZrO2 nanoparticles by the AJS method, with the final goal of finding a biomaterial for bone/periodontal tissue engineering, with the presence of bioceramic as an environmental cues signal needed to guide osteoblast cell responses.
