# Preclinical Performance of Customized Polycaprolactone-Based Hybrid Bone grafts
## 1 Introduction  
The periodontal ligament is a connective tissue that is located between the root cement and the internal cortical of the alveolus. In this tissue, stem cells (PDLSCs) with the ability to differentiate into cells of the periodontal ligament are present and have different functions such as dental support, supplying nutrients and maintaining the homeostasis of the teeth through continuous regeneration [1, 2, 3]. On the other hand, the alveolar bone is a mineralized connective tissue made up of three types of cell lines: osteoblasts, osteoclasts, and osteocytes. It is a dynamic tissue that undergoes constant remodeling. This regeneration is carried out through three phases: the first consists of resorption and is carried outthrough osteoclasts; the second phase of bone formation is the transition period, in which bone formation and destruction take place at the same time; and the third phase is that of bone formation only through osteoblasts [3]. This regeneration cannot always be carried out, and therefore, the bone cortical is destroyed. Bone loss of the upper and lower jaws is mainly caused by pathogenic microorganisms, environmental factors, bad habits such as smoking, genetic factors, or a lack of replacement after tooth loss. This issue of bone loss has led to the development of different techniques to promote osteogenesis and thus combat the defect, since bone is a dynamic tissue. Some of these techniques include bone grafting and the use of scaffolds, stem cells, growth factors, and other biomaterials [4; 5]. The primary function of the material in these techniques is to stimulate the regeneration of bone tissue in areas that are affected by defects (such as bone loss in periodontitis) by degrading in the same place to facilitate the replacement of the material by newly formed bone tissue. Nanocomgiate biomaterials are relatively novel and consist of a polymeric and biodegradable structure that includes nano-sized materials with a bioactive function [6]. The biomaterial characteristics that must be considered are its chemical composition; biological characteristics, such as providing osteoinduction and biocompatibility; biodegradation; and manufacturing process. Biomaterials that are used in bone tissue engineering can be degradable or non-degradable and synthetic or natural. Several materials are used today. Natural polymers: these are polymers obtained from natural substances. The main characteristic of these types of materials is their great biocompatibility; however, they have different disadvantages, such as procurement difficulties, production limitations, and their high cost. These types of polymers include collagen, gelatin, fibrinogen, or polysaccharide polymers [7]. Synthetic polymers: these are polymers that are artificially formed through chemical processes. These polymers have a longer storage time and higher production capacity and can achieve physical properties that are very similar to those of bone. Some polymers, such as polylactic acid (PLA), polycaprolactone (PCL), and polyglycolic acid (PGA) [8], are modified with other substances, such as hydroxyapatite. PCL is a linear synthetic polymer and used as a biomaterial in the field of health due to its beneficial properties such as porosity, slow degradation (thus offering greater load support), high biocompatibility, and lower release of acidic products compared with other polymers. However, pure PCL has some disadvantages. Because it is a hydrophobic material, it lacks the osteogenic potential for the formation of bone tissue; for this reason, PCL has been combined with different inorganic materials to improve its weaknesses. This is how the combination of PCL with hydroxyapatite (HA) nanocrystals emerged. This mixture of both materials offers mechanical and biological improvements to reduce its limitations, making it a promising material in scaffolds [9]. Strontium has also been used in combination with PCL due to the improvement in biological and osteoinductive properties that it offers for bone formation [10].