Elsevier

Chemical Engineering Journal

Volume 366, 15 June 2019, Pages 112-122
Chemical Engineering Journal

Directly photopatterning of polycaprolactone-derived photocured resin by UV-initiated thiol-ene “click” reaction: Enhanced mechanical property and excellent biocompatibility

https://doi.org/10.1016/j.cej.2019.02.045Get rights and content

Highlights

  • We report a photocured resin with enhanced mechanical property and excellent biocompatibility.

  • The resin can be photocured via UV through thiol-ene “click” chemistry.

  • We show the facile fabrication of high-resolution patterns (∼5 μm) using photolithography.

  • The technology is simple, versatile and has potential in bioengineering field.

Abstract

This paper reports a novel routine for the fabrication of a polycaprolactone-derived (PCL-derived) photocured material cross-linked by pentaerythritol tetra (PETMP) with enhanced mechanical property and excellent biocompatibility. The photocured material is cross-linked via UV irradiation through thiol-ene “click” chemistry. The main novelty of this technique is the facile fabrication of high-resolution patterns (∼5 μm) using photolithography, and without adding photo-initiators. The photocured material is studied regarding to its thermal property, mechanical property and cytocompatibility. DSC and DMA suggest that the flexibility and toughness of PCL-derived photocured material have improved. Accordingly, the PCL-derived photocured material achieves enhanced mechanical property (with the increase of PCL segment content from 0 to 38.0%, the photocured samples monotonically increased their breaking strength from 0.62 to 3.10 MPa and Young’s modulus from 1.39 to 9.22 MPa). Due to the incorporation of the PCL-derived copolymer, the material shows excellent affinity to cells, which is demonstrated by the cell proliferation and release of LDH. The hemolysis ratio of PCL-derived photocured materials is all <5%, while the PEGDA photocured material is ∼17%. It can also be observed that PCL-derived photocured material will improve the biocompatibility and reduce biotoxicity compared with PEGDA. This facile route for synthesis of biocompatible photocured resin with micrometer-resolute patterns has a good impact in bioengineering and biomedical fields.

Graphical abstract

In order to achieve a photocured resin with enhanced mechanical property and excellent biocompatibility, we have investigated a PCL-derived photocured material via UV through thiol-ene “click” chemistry and this facile route for fabrication of high-resolution patterns (∼5 μm) has a good impact in bioengineering and biomedical fields.

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Introduction

UV-curable rapid prototyping technology is a fast developing “green” technology. It has the advantages of high reaction efficiency, quick reaction speed, energy conservation and less organic volatile (VOC), thus photocurable polymers have a unique advantage in biomedical applications [1], [2], [3], [4], [5], [6]. Resins used while fabricating scaffolds for tissue engineering require possessing good biocompatibility and high resolution structure [7], [8], [9]. Recently, micropatterned resins, as cell culture substrates or microactuators are gaining attentions in bioengineering [5], [10]. UV irradiation is the facile fabrication of micropatterned resins by photolithography. For example [11], [12], [13], thiol-ene “click” reaction by UV irradiation could prepare micrometer-resolute hydrogel patterns with tailored architecture and multi-responsive properties.

However, most of the photocured resin involves large amounts of small molecules, such as photo-initiator, solvents and so on, which affect biological toxicity because of incomplete polymerization and organic residue [14], [15], [16]. Currently, there are abundant photocurable monomers [17], [18], [19], [20], [21], [22] that have been developed and commonly been applied in bioengineering and biomedical fields. The photocurable monomers like poly(ethylene glycol) diacrylate (PEGDA), hyaluronic acid (HA) and their derivatives, dextran, and PEGDA [17], [23], [24] have relatively higher commercial value because of their low price and high product maturity. These are widely used as crossing agents to prepare hydrogels or photocurable resins. They have potential applications in the fields of neural prosthetic devices, biosensors and drug delivery [25], [26], [27], [28]. Although the use of PEGDA has been relatively matured, there are still some unsolved problems. One of the problems is that PEGDA has poor toughness and ductility although it possesses strong mechanical properties. Another problem is that its biological toxicity is relatively high, that limits its further commercialization in the bioengineering [29], [30].

Caprolactone (CL), another widely used monomer for injectable drug-delivery system, cell culture, etc., has a good biocompatibility and elasticity [31], [32], [33], [34]. For example, Ai Ping Zhu’s team have prepared a foldable micropatterned hydrogel film made from PCL-b-PEG-b-PCL-DA by UV embossing, and the hydrogel was found to have good biocompatibility compared with PEGDA hydrogel [35]. Therefore, the combination of caprolactone and PEGDA can not only improve the biotoxicity and degradation performance of PEGDA, but also have potential to produce high precision products by 3D printing technology [5]. For example, researchers were able to produce a high resolution (<10 µm) tissue engineering scaffold by developing the structure of polycaprolactone-derived (PCL-derived) aliphatic copolymers initiated by two-photon polymerization (2PP). However, the device is very expensive and the rate of molding is slow. Therefore, it is urgent to develop a photocured material by UV rapid prototyping technology with high resolution, low cytotoxicity, and suitable mechanical properties [8], [32].

Herein, our group provides a novel routine for the preparation of the photocured material with excellent biocompatibility and enhanced mechanical property. We discovered that with the incorporation of the photocurable PCL-derived copolymer into PEGDA resin, the biotoxicity and mechanical property of PEGDA could be improved. Scheme 1A shows a general procedure to prepare the photocurable PCL-derived copolymer. The precursor was cross-linked by thiol-ene “click” reaction (Scheme 1B). The mercaptan group was used as the crosslinking agent to enhance the mechanical properties of the material and reduce the residue of small molecular initiator [11], [12], [36]. The feed reactants were all liquid in this methodology, which enabled the reaction with no solvent. Besides, thiol-ene polymerization can be carried out under the mild condition, because the reaction is insensitive to environmental conditions and has high reaction efficiency. This method has the advantages of simplicity, versatility and has no risks of contamination. The performance of PCL-derived photocured material by UV-initiated thiol-ene “click” reaction was greatly improved: (1) The mechanical strength and toughness of the photocured materials was enhanced significantly; (2) “Click” chemistry gave it the advantage of high precision patterning; (3) The biocompatibility of the photocured materials was greatly improved.

Section snippets

Materials

Poly(ethylene glycol) (PEG, Mn = 200), calcium hydride (CaH2), caprolactone (CL), acryloyl chloride, poly(ethylene glycol) diacrylate (PEGDA), pentaerythritol tetra(3-mercaptopropionate) (PETMP), 2,2-dimethoxy-2-phenylacetophenone (DMPA) and stannous octoate (Sn(Oct)2) were purchased from Aladdin Company (China). Toluene was purchased from Hangzhou Shuanglin Chemical Reagent Co., and ethanol was purchased from Zhejiang Hannuo Chemical Technology Co., Ltd.

Synthesis of PCL/PEG/PCL(PCEC)

A biodegradable triblock polyetherester

Synthesis and characteristic of precursor

As shown in Scheme 1A, a controlled ring-opening polymerization initiated by the hydroxyl group of the PEG molecule under the existence of Sn(Oct)2 could be obtained by controlling the content of PCL and the time of polymerization [33]. To confirm the formation of PCEC and ene-PCEC copolymers, 1H NMR was performed and the results were shown in Fig. 1. In Fig. 1A, peaks at the chemical shifts of 3.72 ppm and 4.06 ppm were assigned to methylene protons of single bondCH2CH2Osingle bond in PEG units and single bondCOOCH2single bond in PCL

Conclusions

In a summary, a facile method for the preparation of photocured material with excellent biocompatibility and enhanced mechanical property was demonstrated. It consisted cross-linked and micropatterned photocurable polymers through thiol-ene “click” chemistry via UV irradiation, without adding initiators. In this work, the control of the photocured material’s mechanical property and cell behavior depended on the content of PCL segment and the molecular weight of ene-PCEC copolymer. The main

Acknowledgements

This study was funded by the Natural Science Foundation of China (Nos. 81670433 and 81300236), the Natural Science Foundation of Zhejiang Province (Nos. LY16E030012, LY17E030006, LY18E030009 and LY19E030007), the Medical Scientific Research Foundation of Zhejiang Province (2016KYA097) and the Xin Miao Talent Program of Zhejiang Province (No. 2018R403052).

References (44)

  • Marga C. Lensen et al.

    Micro- and nanopatterned star poly(ethylene glycol) (PEG) materials prepared by UV-based imprint lithography

    Langmuir ACS J. Surfaces Colloids

    (2007)
  • K.W. Lee et al.

    Poly(propylene fumarate) bone tissue engineering scaffold fabrication using stereolithography: effects of resin formulations and laser parameters

    Biomacromolecules

    (2007)
  • A. Sigen et al.

    Hyperbranched PEG-based multi-NHS polymer and bioconjugation with BSA

    Polymer Chem.

    (2017)
  • B. Chollet et al.

    Multiscale surface-attached hydrogel thin films with tailored architecture

    ACS Appl. Mater. Interfaces

    (2016)
  • B. Chollet et al.

    Tailoring patterns of surface-attached multi-responsive polymer networks

    ACS Appl. Mater. Interfaces

    (2017)
  • T.O. Machado et al.

    Thiol-ene polymerisation: a promising technique to obtain novel biomaterials

    Eur. Polymer J.

    (2016)
  • L. Chang et al.

    Synthetic melanin E-ink

    ACS Appl. Mater. Interfaces

    (2017)
  • J. Wei et al.

    Novel highly efficient macrophotoinitiator comprising benzophenone, coinitiator amine, and thio moieties for photopolymerization

    Macromolecules

    (2009)
  • B. Gacal et al.

    Synthesis and characterization of polymeric thioxanthone photoinitatiors via double click reactions

    Macromolecules

    (2008)
  • O. Kufelt et al.

    Hyaluronic acid based materials for scaffolding via two-photon polymerization

    Biomacromolecules

    (2014)
  • J. Decock et al.

    In situ photo-patterning of pressure-resistant hydrogel membranes with controlled permeabilities in PEGDA microfluidic channels

    Lab on A Chip

    (2018)
  • L. Ouyang et al.

    A generalizable strategy for the 3D bioprinting of hydrogels from nonviscous photo-crosslinkable inks

    Adv. Mater.

    (2017)
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    Yazhi Zhu, Jian Shen and Zheng Gu contributed equally to this work.

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