Urethane dimethacrylate-based photopolymerizable resins for stereolithography 3D printing: A physicochemical characterisation and biocompatibility evaluation

Abstract

Vat photopolymerisation (VP) three-dimensional printing (3DP) has attracted great attention in many different fields, such as electronics, pharmaceuticals, biomedical devices and tissue engineering. Due to the low availability of biocompatible photocurable resins, its application in the healthcare sector is still limited. In this work, we formulate photocurable resins based on urethane dimethacrylate (UDMA) combined with three different difunctional methacrylic diluents named ethylene glycol dimethacrylate (EGDMA), di(ethylene glycol) dimethacrylate (DEGDMA) or tri(ethylene glycol) dimethacrylate (TEGDMA). The resins were tested for viscosity, thermal behaviour and printability. After printing, the 3D printed specimens were measured with a digital calliper in order to investigate their accuracy to the digital model and tested with FT-IR, TGA and DSC. Their mechanical properties, contact angle, water sorption and biocompatibility were also evaluated. The photopolymerizable formulations investigated in this work achieved promising properties so as to be suitable for tissue engineering and other biomedical applications.

Introduction

Over the last decade, three-dimensional printing (3DP) has experienced rapid growth and demonstrated great potential in different fields such as bioengineering, pharmaceuticals, microfluidics and electronics [1]. Among the 3DP approaches, the ones based on photopolymerisation such as stereolithography (SLA) and digital light processing (DLP) have attracted attention due to their easiness of use and quick production speed [2]. SLA was the first 3DP technology to be developed and subsequently patented by Charles Hull in 1984. This approach involves layer-by-layer photopolymerisation by crosslinking reactions of a photopolymerizable liquid through the use of a UV laser. Once a layer is polymerised, the building platform is lowered again into the photopolymerizable liquid and the cycle is repeated until the completion of the 3D structure [3, 4]. SLA allows the production of different 3D objects with a high degree of reproducibility offering an accurate final microstructure and geometry. However, it often requires a long time for post-processing and there is a low number of materials appropriate for SLA healthcare applications [3].

The starting material necessary for vat photopolymerisation (VP) 3DP is a mixture of three main components; a monomer or oligomer, which comprises reactive groups essential to build the polymeric network. The most used are acrylate and methacrylate as they are characterised by a fast reactivity. The physical and mechanical properties of the 3DP specimen will be determined by the backbone of the monomer. Another essential component is the photoinitiator, which the main function is to initiate the reaction as a consequence of light absorption. Sometimes a dye or colourant is also added in order to control the light penetration during the 3DP process and ensure high resolution [5].

Numerous photopolymerizable resins have been produced and many are commercially available, with the majority composed of multi-functional monomers based on methacrylate or acrylic esters [6]. The main drawback related to the application of photopolymerisation in the healthcare sector is the lack of availability of FDA-approved biocompatible photopolymerizable materials mainly related to the presence of unreacted products after the polymerisation (monomer, photoinitiator, and additives) [2]. Thus, there is an increasing demand for the development of novel photocurable resins that can be employed in the medical and pharmaceutical sectors [6]. One of the most employed biocompatible materials in VP 3DP is urethane dimethacrylate. Urethane dimethacrylate [7,9,9-trimethyl-4,13-dioxo-3,14-dioxa-5,12-diaza-hexadecane-1,16-diylbis(2-methylacrylate)] is a transparent, odourless, and hydrophobic compound mostly used in the photopolymerisation of dental resins, biomaterials, self-healing materials, and luminescent polymers [7]. For example, in a previous study, diurethane dimethacrylate (UDMA) was mixed with glycerol dimethacrylate (GDMA) and quaternary ammonium methacrylate to obtain an antimicrobial resin suitable for SLA 3DP, with the potential to be used for dental and orthopaedic applications [8]. UDMA possesses a high molecular weight and high viscosity, which could interfere with successful printing. For this reason, it is preferable to combine this monomer with a diluent able to decrease its viscosity and make it more suitable for printing. One of the mostly common diluents employed in association with urethane dimethacrylate is triethylene glycol dimethacrylate (TEGDMA) [9]. The latter is a hydrophilic, low-viscosity, difunctional methacrylic monomer employed as a crosslinking agent [10].

The potential of SLA 3DP in the healthcare sector was investigated by many research groups. SLA 3DP was used to develop different oral dosage forms such as immediate-release tablets, modified-release tablets and tablets containing multiple APIs [11,12,13]. Moreover, different groups explored its potential in the manufacturing of topical drug delivery systems, such as microneedles and topical films [14,15,16]. Finally, bio-medical scaffolds, dental prosthetics and medical devices were successfully manufactured by stereolithography 3DP [8, 17,18,19] .

Most of the previous studies employing SLA 3DP in the development of healthcare products use commercially available photocurable resins. Just few works present an investigation on the formulation. The most studied photocurable polymers in the healthcare sector have been poly (ethylene glycol) diacrylate (PEGDA) [11], poly (ethylene glycol) dimethacrylate (PEGDMA) [20] and poly (propylene fumarate)/diethyl fumarate (PPF/DEF) [21]. Preparing a photopolymerizable formulation by selecting the appropriate raw materials could be convenient leading to a reduction of the costs.

Starting from this background, the aim of this work is to investigate the suitability for SLA 3DP and biocompatibility of novel photopolymerizable resins based on UDMA combined with three different difunctional methacrylic diluents (e.g., tri(ethylene glycol) dimethacrylate—TEGDMA, di(ethylene glycol) dimethacrylate—DEGDMA, and ethylene glycol dimethacrylate—EGDMA). The resins were characterised in terms of viscosity and thermal behaviour. Spectroscopy was employed to evaluate the conversion of the methacrylate groups after printing and after curing. The mechanical properties, water sorption, contact angle and biocompatibility of the 3D-printed specimens were also investigated.

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Pitzanti, G., Mohylyuk, V., Corduas, F. et al. Urethane dimethacrylate-based photopolymerizable resins for stereolithography 3D printing: A physicochemical characterisation and biocompatibility evaluation. Drug Deliv. and Transl. Res. (2023). https://doi.org/10.1007/s13346-023-01391-y

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