Material PropertiesMultiscale structural characterization of biocompatible poly(trimethylene carbonate) networks photo-cross-linked in a solvent
Graphical abstract
Introduction
Biodegradable polymer networks have great potential in biomedical applications due to their biocompatibility and biodegradability [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15]. More specifically, tough elastomeric polymer networks are of interest as bulk materials [12], [16], [17], [18], [19], [20], [21]. Elastomeric polymer networks can be designed to exhibit mechanical properties required for their intended application, especially soft tissues [22]. Much work has been done to improve the toughness of the elastomeric networks, but it remains a challenge to obtain elastomers that are both degradable and tough [18].
To improve the toughness of elastomeric networks, the growth of micro-cracks must be hindered [23]. This has been extensively studied for both natural and synthetic elastomers, though many of these studies have been performed with non-degradable elastomers such as polyisoprene and poly(dimethyl siloxane) (PDMS) [24], [25], [26], [27], [28], [29]. The formation of micro-cracks in these networks was slowed down by introducing crystallizable domains into the polymer network, crosslinking in solvent, and crosslinking chains with bimodal chain length distributions.
Tough, biodegradable elastomeric networks have been preparedvia the photo-crosslinking of methacrylate-functionalized PTMColigomers (PTMC macromers) and acrylated poly(e- caprolactone-co-D,L-lactide) (P(CL-co-DLLA)) oligomers [16], [18], [30]. Such networks are formed by adding a photo-initiator which forms radical species upon light irradiation [31]. These radical species can initiate polymerization of the (meth)acrylate end-groups of the macromers, creating poly(methacrylate) kinetic chains as the networks are formed. In the case of PTMC-networks, toughness increased with macromer molecular weight [16]. In addition, the preparation of bimodal PTMC networks resulted in a significant increase in toughness [19]. For both PTMC- and P(CL-co-DLLA) macromers, crosslinking in solution resulted in less rigid networks that demonstrated increasing elongation with decreasing macromer concentrations, resulting in superior elastomer toughness [18], [30].
It has been suggested that the presence of solvent during crosslinking results in disentangled chains prior to crosslinking formation, which in turn leads to simpler topologies in the networks [25]. The crosslinks of such networks are more likely to be both spatial and topological neighbors as compared to networks prepared in bulk. In addition, networks prepared in solution have fewer chain-junction and inter-chain entanglements. The polymer chains in these networks are less-firmly embedded in the network structure; subsequently these networks deform more non-affinely. In order to fully understand the influence of crosslinking in solution on the macroscopic properties of elastomeric networks, the thermomechanical behavior and structural morphology of these networks need to be fully studied.
To facilitate this, a macroscopic experimental approach combining tensile testing, DSC and DMA analyses, and Time Domain Double Quantum NMR was undertaken in this work. Tensile tests yielded the macroscopic mechanical resistance of the studied PTMC samples, while DSC and DMA allowed the evolution of molecular mobility to be analyzed via observation of the glass transition temperature. Moreover, DMA allowed the characterization of the mechanical crosslink density of PTMC networks with varying molecular weight and solvent concentrations [32], [33]. These studies were complemented by Time Domain NMR. This specific technique has been principally used to characterize the structure, morphological organization and molecular mobility of polymeric networks [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45]. Double-Quantum sequences have been proven to effectively characterize elastomeric-like polymer networks, specifically their molecular mobility, crosslink density , and chain defect concentration [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], in addition to the evolution of these properties with temperature [58], [59], chemical [60], [61], [62] and physical modifications [63], and thermal aging [64], [65]. This is made possible due to the ability of this technique to discriminate dynamical and structural effects, permitting semi-local structural features of networks to be recovered from local dynamical measurements.
More extensively, Time Domain NMR has been efficiently used in combination with DMA analyses to study the relationship between the structure of PTMC networks of various macromer molar masses, and their macroscopic thermomechanical behavior [66]. Therefore, this work is a logical evolution of this previous study. By applying the same approach to analyze the influence of polymer concentration during PTMC network formation, we aim to deepen the understanding of the influence of intrinsic polymer structure on the macroscopic behavior of PTMC networks, which in turn will provide deeper insight regarding how to chemically tailor network structure, so as to better regulate and adjust PTMC specific macroscopic properties. PTMC networks were chosen for this study, as such networks are extensively studied for a range of biomedical applications requiring different properties, such as intervertebral disks [67], meniscus implants [17] and bone implants [20]. Its biocompatibility has been shown previously with, among others, synovium derived cells [68], mesenchymal stem cells [69], and chondrocytes [70] in vitro and in several studies in vivo [68], [71], [72].
Section snippets
Materials
Trimethylene carbonate (TMC) monomer was purchased fromHuizhou ForYou Medical Devices Co. (China). Hydroquinone,methacrylic anhydride, tin(II) 2-ethylhexanoate (Sn(Oct)2), Trimethylol propane (TMP), and triethylamine were purchased from Sigma (USA) and used as received. Dichloromethane and chloroform were obtained from Merck (Germany), and d-chloroform was purchased from VWR. Ethanol was obtained from Altia oyj (Finland). TPO-L (2,4,6-trimethylbenzoylphenyl phosphinate) was obtained from
Swelling characterization
The volume degree of swelling q was determined in triplicate at room temperature by swelling rectangular shaped specimens (5 × 5 × 1 mm) in chloroform for 24 h, which was sufficient time to reach solvent sorption equilibrium. The q was calculated from Eq. (1) where is the mass of the swollen networks, the mass of the networks after drying, and and the densities of PTMC (=1.31 g/cm) [16] and chloroform (=1.48 g/cm), respectively.
DSC analysis
The thermal
Results and discussion
Three-armed PTMC macromers were synthesized via the ring-opening polymerization of TMC into PTMC oligomers followed by functionalization with methacrylic anhydride. By adjusting the monomer-to-initiator ratio, oligomers with three different molecular weights were obtained. Table 1 shows the obtained oligomer molecular weights as confirmed by H-NMR. The subsequent functionalization resulted in macromers with a degree of functionalization of 86%. In Figure SI.4 (Support Information), a typical
Conclusion
This investigation has highlighted the advantages of combining a multiscale experimental approach to better understand the macroscopic mechanical properties of PTMC networks from their intrinsic structural morphology. By combining tensile testing, DMA analyses and NMR measurements it was shown that PTMC crosslink density depended on the polymer content during the crosslinking reaction; the lower the polymer content, the lower the crosslink density value. This was systematically observed
CRediT authorship contribution statement
Bas van Bochove: Conceptualization, Methodology, Software, Data curation, Writing - original draft, Visualization, Investigation, Supervision, Writing - review & editing. Steve Spoljaric: Conceptualization, Methodology, Software, Data curation, Writing - original draft, Visualization, Investigation, Supervision, Writing - review & editing. Jukka Seppälä: Conceptualization, Methodology, Software, Data curation, Writing - original draft, Visualization, Investigation, Supervision, Writing - review
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
This work made use of Aalto University Bioeconomy Facilities. The authors are deeply grateful towards Cédric Lorthioir for sharing the optimized Solid State NMR pulse sequence used in this work and towards Paul Sotta for fruitful discussions.
Funding
This project was funded by an Aalto University postdoctoral researcher project in synthesis of novel biopolymers (Finland) and by the Centre National de la Recherche Scientifique CNRS (France) . The authors declare no conflict of interests.
References (78)
- et al.
Sterilization, storage stability and in vivo biocompatibility of poly(trimethylene carbonate)/poly(adipic anhydride) blends
Biomaterials
(2000) - et al.
Thermo-sensitive transition of monomethoxy poly(ethylene glycol)-block-poly(trimethylene carbonate) films to micellar-like nanoparticles
J. Control. Release
(2006) - et al.
Introduction of enzymatically degradable poly(trimethylene carbonate) microspheres into an injectable calcium phosphate cement
Biomaterials
(2008) - et al.
Combined and sequential delivery of bioactive VEGF165 and HGF from poly (trimethylene carbonate) based photo-cross-linked elastomers
J. Control. Release
(2010) - et al.
Solid tumor penetration by integrin-mediated pegylated poly(trimethylene carbonate) nanoparticles loaded with paclitaxel
Biomaterials
(2013) - et al.
Nanoparticles of 2-deoxy-D-glucose functionalized poly(ethylene glycol)-co-poly(trimethylene carbonate) for dual-targeted drug delivery in glioma treatment
Biomaterials
(2014) - et al.
Flexible, elastic and tear-resistant networks prepared by photo-crosslinking poly(trimethylene carbonate) macromers
Acta Biomater.
(2012) - et al.
Tough biodegradable mixed-macromer networks and hydrogels by photo-crosslinking in solution
Acta Biomater.
(2016) - et al.
Dependence of properties of swollen and dry polymer networks on the conditions of their formation in solution
Polymer
(1985) - et al.
Nuclear magnetic resonance approach to fractal chain structure in molten polymers and gels: Characterization method of the spin-system response
Polymer
(1988)