**1. Introduction**

Bioactive glass-based biomaterials (BGs) have shown successful applications in bone tissue repair and regeneration due to their good biocompatibility, osteoconductivity, and bone-bonding ability when implanted in vivo without any interfaces of fibrous connective tissue [1–4]. This high bone-bonding ability with living bone tissue is considered to be highly associated with their bone-like apatite layer formation [5]. Because BG has a high conductivity and bone bondability, and enhanced bone regeneration potential, the application of BG-based biomaterials in bone tissue regeneration has widely attracted attention in recent years [6]. However, pure BG is limited for use in bone tissue engineering applications due to its inherent brittleness and low flexibility. Furthermore, it is difficult for BG to form various shapes for improving in vivo applications. Hence, there is a considerable need to design and fabricate highly bioactive glass-based biomaterials with tough mechanical properties for bone tissue engineering applications.

As compared with inorganic bioactive glass materials, biopolymers exhibit unique biological physical and biochemical properties, such as high toughness, electrometric properties, greater capacity for body fluid absorption, and better gel forming capacity [7]. Hence, it is reasonable to incorporate inorganic nanoparticles into a polymer matrix to produce nanocomposites with optimized physicochemical properties, such as bioactive

**Citation:** Chen, J.; Que, W.; Lei, B.; Li, B. Highly Bioactive Elastomeric Hybrid Nanoceramics for Guiding Bone Tissue Regeneration. *Coatings* **2022**, *12*, 1633. https://doi.org/ 10.3390/coatings12111633

Academic Editor: Jun-Beom Park

Received: 5 October 2022 Accepted: 25 October 2022 Published: 27 October 2022

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glass micro-nanoscale particles-poly(caprolactone) (MNBG-PCL) biomaterials [8,9]. Actually, the addition of bioactive phases significantly improves the mechanical modulus, biomineralization activity, and biocompatibility in osteoblasts of the PCL matrix [10–12], but a particle-based inorganic phase is an obstacle to the enhancement of the strength and toughness of the polymer simultaneously due to its poor interactions [13]. Recently, molecular-level-based silica-based glass sol was added into a polymer solution to synthesize the bioactive glass–polymer hybrid biomaterials, including BG-PCL, BG-gelatin, BG-chitosan, and BG-poly(ethylene glycol) [14–16]. In the case of the molecular hybridization, the obtained hybrids show the stable mechanical property, biomineralization activity, and osteoblast biocompatibility. As a result, the development of silica-based hybrid polymer biomaterials for effective bone tissue regeneration applications is highly promising [17].

In the guiding bone tissue regeneration application, the guiding membrane biomaterials are crucial to enhance the tissue repair through preventing the invasion of external protein and cells [18]. The ideal guiding membrane should be tough, bioactive, and easyhandling. In our previous work, poly(dimethylsilicone)-bioactive glass-PCL (PBP) hybrid membranes without fracture were successfully fabricated via a sol-gel process, which exhibited a controlled surface morphology, mechanical property, and biomineralization [10]. There is still much space to improve the apatite-forming ability (biomineralization activity) and osteoblast biocompatibility of the PBP hybrid membrane. Human bone tissue is a typical organic–inorganic composite consisting of nano-crystalline hydroxyapatite (nHA) and collagen polymer. Artificial HA has received more attention as a bioactive ceramic material in bone replacement and repair applications due to its similar structure and composition to natural apatite. It was selected as an inorganic additive for biomimicking. In addition, some published works suggest that HA supplementation can provide pH buffers for acid-released production [19–21]. In this regard, incorporating nanoscale HA into biomaterials may be a promising option for enhancing biomineralization activity and osteoblastic ability.

In this study, the crack-free nHA-PBP hybrid membranes are prepared via a typical sol-gel method. The effects of the addition of nanoscale HA (nHA) on the structural property and biomineralization activity of the PBP hybrids are also investigated. In addition, the purpose of this study is to analyze the effects of nHA-PBP hybrid membranes with different HA loading concentrations on cell attachment to examine the basic biocompatibility of hybrid materials. It is anticipated that the incorporation of nHA can significantly improve the biomineralization and osteoblastic biocompatibility of the nHA-PBP hybrid biomaterials.

#### **2. Experimental**

## *2.1. Materials*

Tetraethoxysilane (TEOS, Si(OC2H5)4), calcium nitrite (Ca(NO3)2·4H2O), isopropylalcohol (IPA), tetrahydrofuran (THF), dichloromethane (DCM), and hydrochloric acid (HCl, 35%) were obtained from Guanghua Chemical Factory Co., Ltd. (Guangzhou, China). Polydimethylsiloxane (PDMS, HO-[Si(CH3)2-O-]nH, Mn = 1100) was provided by Alfa (Alfa, Ward Hill, MA, USA). Poly(caprolactone) (PCL, (C6H10O2)n) (Mn = 80,000) was supplied by Sigma-Aldrich (Sigma-Aldrich, St. Louis, MO, USA). Nano-hydroxyapatite (nHA) powder (consisting of loose aggregates of approximately 100 nm crystals) was purchased from Alfa Aesar (Ward Hill, MA, USA)

#### *2.2. Synthesis of nHA-PBP Hybrid Membrane*

The nHA-PBP hybrid membranes were synthesized. Briefly, 10 mL IPA and 20 mL THF were combined to form co-blended solvents, TEOS (6.5 g) was first dissolved in this aqueous solution. Thirty minutes later, 1.5 mL of 35% HCL, 12 mL of water, and 2.2 g of PDMS were added into the solution for completely catalyzation and hydrolyzed reaction for 30 min. Then, the Ca(NO3)2·4H2O, IPA, and H2O were added to the aforementioned solution. The generated bioactive PDMS-BG sol was then mixed with the DCM solution of PCL and further stirred for 30 min. To obtain the nHA-PBP hybrid sol, the predetermined containing nHA (0, 20, 30, 40, and 50 wt% relative to the PCL polymer) was added and vigorously stirred for 20 h. Then, the mixture was poured into the Teflon dishes and dried at 37 ◦C for 12 h to form the nHA-PBP mixed gel. Finally, after heating the mixed gel at 60 ◦C for 12 h, the nHA-PBP hybrid membranes were obtained.
