Characterization of Eudragit Nanoparticle-Tailored β-Cyclodextrin/Thiolated Sodium Alginate/Polyethyleneglycol Polymer Hybrid as a Potential Bone Tissue Engineering Scaffold

Degeneration and damage of tissues can be caused by disease, injury, and trauma in the human body, which requires treatment to facilitate regeneration, replacement, and repair. Treatment modalities involved with tissue transplantation, like autograft or allograft, are associated with limitations such as the methods are expensive, painful, risky of rejection, and the possibility of infections [1]. The field of tissue engineering offers an alternative approach, where damaged tissue can be regenerated, rather than replaced, through the development of biological substitutes that maintain, restore, and recover tissue function. The scaffolds are capable of providing a suitable environment for tissue regeneration and primarily act as a template for the growth and development of new tissue [2].

Bone is a dynamic and well-vascularized tissue that constantly renews itself through the coordinated activity of osteoblasts and osteoclasts. Normally, bone has an excellent ability to heal on its own, and small defects can be repaired without the need for external support. However, when the defect is large, usually more than 2 cm in humans, the natural healing capacity is not enough to fully restore the bone’s structure and function [3]. In such cases, medical intervention becomes necessary, and scaffolds for bone tissue engineering can provide critical support for regeneration.

Alginate is a safe, biodegradable, and biocompatible polysaccharide material that has applications in vast areas of food science, drug delivery, cosmetics, and tissue engineering. Alginate has numerous biomedical applications with nontoxic character and excellent biocompatibility, and its potential is still under investigation with the development of novel composites [4]. An interesting approach to modulating the properties of a composite and scaffold is tailoring them with nanoparticles. The technique of development of nanoparticle-enriched composite and scaffold material can incorporate potential therapeutic features in the field of regenerative medicine [5].

Polyethylene glycol is a type of polyol polymer that exhibits suitable properties in scaffolds and composites for tissue engineering. Its biodegradability, nontoxicity, nonantigenicity, and nonimmunogenicity towards proteins and cells are considered to be its main advantages [6]. PEG has the capability of suppressing the non-specific uptake of nanomaterials via a cell membrane. The molecular weight selection of PEG is an important parameter as it plays a significant role in the biomineralization process during the action of a scaffold. As the molecular weight of PEG increases, the solubility of the polymer in water decreases, and this property plays a significant role in the biological function of scaffolds, composites, and drug delivery for tissue engineering applications [7].

Cyclodextrins are glucose-based, naturally existing cyclic oligosaccharides. β-CDs, among them, possess seven glucose units and have a significant use in the field of materials due to their ease of application and availability. Cyclodextrins have the efficiency of entrapping lipophilic molecules in a hydrophilic environment, and this property plays a significant role in the development of scaffolds in tissue engineering [8]. Scaffolds fabricated with β-CD have been shown to promote tissue engineering ability by elevating the oxygen concentration in tissue engineering constructs by regulating the self-assembly of collagen [9, 10]. It is also used in drug delivery systems where the drug-β-CD conjugate is stabilized by van der Waals forces and allows for prolonged drug release [11].

Eudragit L100 polymers are methacrylic acid–methyl methacrylate copolymers that are biocompatible, film-forming, and show pH-responsive solubility. Since Eudragit L100 remains insoluble at acidic pH but dissolves at pH values above 6, it can be used to preserve the integrity of scaffolds in physiological environments [12]. The incorporation of Eudragit nanoparticles into polymeric scaffolds can enhance the mechanical strength, modulate the degradation, and regulate the water uptake. The advantage of the hydrophilic and hydrophobic interactions of the copolymers makes it a suitable modifier for hybrid scaffolds for bone tissue engineering [13].

Modifying biomaterials to mimic the cellular environment can enhance their performance in tissue engineering. The biomaterials should be modified and guided to replicate the extracellular matrix (ECM) so that they can transport the growth factors and cell adhesive substances in the progression of tissue morphogenesis [14]. Biomaterials for tissue engineering should have a 3-dimensional model to support cell differentiation, proliferation, and cell seeding. Properties of scaffolds, such as porosity, water absorption, and gelling capacity, with optimum morphological features, help them degrade slowly during the formation of ECM. These properties make the scaffolds a vital element, acting as a starting material for cell attachment, proliferation, and the maintenance of their functional properties during in vitro and in vivo tissue engineering [15, 16]. The success of scaffold-oriented tissue engineering depends upon the physicochemical and biological properties of the scaffolds. Due to their capacity to replicate the ECM, naturally derived polymers are preferred over other broad ranges of materials like metals and ceramics in tissue engineering applications. An inappropriate combination of materials in scaffolds may lead to intricate processing, fast degradation, and improper mechanical strength due to inapt porosity [17].

In the present study, we have designed a scaffold material with a combination of TSA, polyethylene glycol, and β-CD, which was functionalized with Eudragit nanoparticles to balance the hydrophilic-hydrophobic property of the scaffold. The developed scaffold was investigated for different physicochemical properties and assessed for its bone tissue engineering ability in silico. The efficacy of the bone tissue regeneration was further evaluated by molecular docking studies.

Materials