Comparative Role of Chain Scission and Solvation in the

Subscriber access provided by UNIVERSITY OF TOLEDO LIBRARIES

B: Biomaterials and Membranes

Comparative Role of Chain Scission and Solvation in the Biodegradation of Polylactic Acid (PLA) Aleena Alex, Nirrupama Kamala Ilango, and Pijush Ghosh J. Phys. Chem. B, Just Accepted Manuscript • DOI: 10.1021/acs.jpcb.8b07930 • Publication Date (Web): 25 Sep 2018 Downloaded from http://pubs.acs.org on September 27, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

The Journal of Physical Chemistry

Comparative Role of Chain Scission and Solvation in the Biodegradation of Polylactic Acid (PLA) Aleena Alex1, Nirrupama Kamala Ilango1, Pijush Ghosh1* 1. Nanomechanics and Nanomaterials Laboratory, Indian Institute of Technology Madras, Chennai-600036, Tamil Nadu, India

*Corresponding author

Associate Professor Department of Applied Mechanics Room: MSB 224A Indian Institute of Technology, Madras Chennai, India. Phone: +91-44-2257-4060 (office) : +91-44-2257-5082 (Lab) Email: [email protected] https://home.iitm.ac.in/pijush/index.html

1

ACS Paragon Plus Environment

The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Abstract The molecular mechanism behind the process of biodegradation and consequently the loss in mechanical properties of Polylactic acid (PLA) requires detailed understanding for the successful designing of various technological devices. In this study, we examine the role of free water and chain scission in this degradation process and quantify the mechanical properties of pristine and nanoparticle-reinforced PLA as it degrades over time. The in-situ mechanical response of the degrading polymer is determined experimentally using nano-Dynamic Mechanical Analysis (nanoDMA). Water present in the polymer matrix contributes to hydrolysis and subsequent scission of polymer chains. Water in excess of hydrolysis, however, alters the load transfer mechanism within the polymer chains. Molecular mechanism study applied in this work provides detailed insights into the relative role of these two mechanisms-i) chain scission and ii) solvation- in the reduction of mechanical properties during degradation. Functional groups such as ester (-COO-) and terminal acid (-COOH) interact with water molecules leading to the formation of water bridges and solvation shells, respectively. These are found to hinder the load transfer between polymer chains. It is observed that, compared to scission, solvation plays a more active role in the reduction of mechanical properties of degrading PLA.

2


Page 2 of 46

Page 3 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


1.0 Introduction Polylactic acid (PLA) is a biodegradable polymer which has attractive technological applications based on its several desirable properties such as biocompatibility, non-toxicity to the human body etc. PLA finds major application in medical implants due to its bioresorbable nature. It is used for the preparation of sutures, bone screws and scaffolding for tissue regeneration 1-12. These varied applications desire different critical properties. For example, higher mechanical properties are desirable for load carrying applications such as bone screws. The slow degradation and lowering of mechanical properties over time are also advantageous in certain cases. For example, the healed bone or tissue gets sufficient time in which the load is gradually transferred from implant to the bone. On the other hand, for scaffolding applications, flexibility is critical 2. In applications where tissue or bone healing rate is fast, it may be desirable for the implant to lose its mechanical properties more rapidly. Thus, it is not only important to investigate various mechanical properties of different isomers of PLA but also to quantify the rate at which they lose their load carrying capacity due to degradation. This loss in mechanical properties at macro length scale is a result of various underlying micro and nanomechanical phenomena. The relationship between polymeric nanostructure and molecular interactions is thus of great interest for the rational design of products with targeted applications. In our study, we have used Poly (D, L-lactic acid) (PDLLA) which is an atactic, amorphous polymer formed by the polymerization of meso-lactide 3, 17, 25. Bioactive ceramics such as hydroxyapatite (HAp) have often been introduced into the PDLLA matrix in order to improve its mechanical properties 2, 10, 26

. In this work, we have referred to the isomer PDLLA as PLA throughout the manuscript.

Different molecular phenomena have been reported which initiate, accelerate, decelerate or inhibit degradation. Several underlying micro and nanomechanical features such as polymer 3



functional group, water absorption, crystallinity, molecular weight distribution, presence of reinforcing particles etc. are altered during degradation. These changes, in turn, alter the resultant mechanical strength of the polymer matrix. It is important to note that most of these factors are coupled. For example, in PLA, degradation occurs due to the breakage of polymeric chains to lower oligomeric lactic acid unit as a result of hydrolysis. Consequently, molecular weight reduces and molecular weight distribution changes 13-15, 18. Since the presence of water is essential for the scission to be triggered, increased water absorption leads to increased scission, consequently altering the molecular weight distribution 4-6. Shirazi et. al (2014) 16 reported that even after extensive scission, the remaining polymer chains in the matrix are long enough to support the mechanical load applied. Thus they reported a time lag between scission of polymer chains and reduction of mechanical strength. However, as time progresses, chains become shorter, finally yielding to the applied load. The position at which scission occurs is also of interest in determining mechanical strength. Scissions near the end of polymer chains lead to the formation of water-soluble oligomers which catalyzes the hydrolysis reaction. This self-catalysis would lead to further scission. However, a random scission at the middle of the polymer chain has a greater impact in reducing the molecular weight and consequently, the mechanical properties 4-6. The kinetics of scission has been described by various statistical models which takes into account parameters such as order of hydrolysis reaction, cross-links per backbone chain, mass fraction of network contained in the backbone etc 19-21. Presence of water in the polymer matrix is another leading cause of reduction of mechanical properties. It has been reported that moisture ingress degrades mechanical properties by three different mechanisms 22-24. Firstly, water diffuses into the micro gaps or free volumes between polymer chains, thus disrupting the load transfer mechanism between the chains. Secondly, the capillary transport of water into the gaps may lead to flaws at the interface between the polymer 4


Page 4 of 46

Page 5 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


and reinforcing material such as fiber or nanocomposites. Thirdly, water may induce swelling behavior which propagates microcracks within the polymer matrix. Water enhances the viscous nature of the polymer matrix as it acts as a plasticizer between the polymer chains leading to higher yield. In addition to these physical mechanisms, in polymers such as PLA, presence of water accelerates hydrolysis and break down polymer chains to lower oligomeric units 4-6, 24. This in turn alters the mechanical properties of polymer matrix. In this work, we emphasise on the two major factors contributing to degradation and reduction in mechanical strength- i) chain scission and ii) solvation. The major objective of this paper is to examine the relative roles of these two mechanisms in the reduction of mechanical strength by decoupling them with the help of molecular modelling. The effect of hydrophilic HAp nanoparticle on enhancing the mechanical properties in the pristine and degraded state of PLA is also investigated. Prior to the understanding of the mechanism, the mechanical properties of degrading PLA were measured applying nano Dynamic Mechanical Analysis (nanoDMA). These observations are later correlated and explained using molecular dynamics simulations. 2. Materials and Methods 2.1 Materials and Film Preparation Poly (D, L lactide) of molecular weight 75,000-120,000 g/mol was supplied by Sigma Aldrich (Product Code: P1691). 500mg of PLA crystals were dissolved in 2.5 ml of tetrahydrofuran (THF) solution. The mixture was placed in a sealed container and immersed in an ultrasonic bath for 1 hour and stirred further using a magnetic stirrer at a rate of 200 rpm until a homogeneous mix is obtained. 1%, 5% and 10 % hydroxyapatite (HAp)/PLA nanocomposites were also similarly prepared with THF. Once the crystals and nanoparticles have completely dissolved, the solution was removed from the magnetic stirrer and cast into a Petri dish. The samples were 5



sealed and placed in the desiccator for 24 hours for the solution to evaporate. All samples were maintained at a temperature of 240C and relative humidity (RH) of 50-60%. Samples used for FTIR and GPC were maintained at a higher humidity (RH 95%) to induce accelerated degradation. All experiments were repeated for at least 3 set of samples. 2.2) Nanomechanical Characterisation The samples used for nanoindentation were initially cast into a glass Petri dish and indentation was performed in-situ without removing them from the container to avoid stress localizations. It was observed that PLA forms a transparent and smooth film surface initially and as time progresses it turns to milky white in color with bubbles visible on the surface. During nanomechanical testing it was ensured that the tests were conducted on the intact portions of the surface. The tests were repeated on a minimum of 10 points on each sample and mean value with standard deviation is reported. 2.2.1 Dynamic Nanoindentation Dynamic nanoindentation or nanoDMA is employed in this work for the determination of storage modulus (E), loss modulus (G), hardness (H) and phase lag (δ). The working principle and property estimation from dynamic nanoindentation are explained in detail in Supporting Information (SI1). Figure 1 shows the loading path adopted for all the dynamic measurements in this work. Frequency sweep load function was applied with the frequency values varying from 200 to 50 Hz. The dynamic load has an amplitude of 1µN since it is normally recommended that the oscillatory load amplitude should ideally be 1/50th of the static load applied 27-29. The reliability of nanoindentation tests is extremely sensitive to a good surface finish. An ideal surface is easy to achieve at the initial stages of degradation (0-20 days) but particularly difficult in later stages and especially in easily degraded samples such as PLA. Hence, at later stages it was ensured that the indented surface is free of bubbles or excessive moisture. Finding an ideal 6


Page 6 of 46

Page 7 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


location in the sample where indentation can be performed and reliable results can be obtained was accomplished by multiple trial and error process involving extensive SPM imaging of the surface, roughness analysis and finally indentation. 2.3 Fourier Transform Infrared (FTIR) Spectroscopy IR spectra were recorded using Bruker Tensor II spectrometer. The measurements were taken using ATR of Zinc Selenide crystal, from wavenumber 400cm-1 to 4000cm-1, at a resolution and scan rate of 4cm-1 and 128 scans respectively.

Figure 1: The frequency sweep loading used for Dynamic nanoindentation. The frequencies at which mechanical properties are plotted are chosen from the start, middle and end of the sweep. 2.4 Gel Permeation Chromatography (GPC) The molecular weight of PLA for different curing time was measured at room temperature on a Waters GPC (Waters, Eschborn, Germany) system with Waters 515 HPLC pump and three Phenomenox columns connected in series (guard column, 500, 103 , and 104 Å; 5 -mm particle size). Waters 2487 dual K absorbance UV detector and 2414 RI detector with Empower software 7



data analysis package supplied by Waters was employed for data analysis. Tetrahydrofuran (THF) at a flow rate of 1ml/min was used as a solvent and narrow molecular weight polystyrene (PS) was used for calibrating the system. The wavelength of 210nm was used for PLA. In accordance to existing literature PLA has absorption at 210nm in the UV region. Same detectors were used for PS calibration as well at 254nm. While applying GPC to PLA using polystyrene as the standard it should be noted that the data reported can only be considered as semi-quantitative. As GPC separates on the principle of hydrodynamic volumes of polymer coils, for a given molecular weight both PS and PLA will have different sizes in the solution. Since polystyrene has an aromatic side chain it will occupy a larger hydrodynamic volume compared to the PLA of similar molecular weight. Thus the retention time of PLA may be under represented especially at lower molecular weights. Hence the reported molecular weights of PLA are not absolute values, but polystyrene equivalent molecular weights. As a result, it was observed that the lower molecular weights obtained for pristine PLA differed from the manufacturer values. However, this data is only used to observe the decreasing trend of molecular weights, as PLA degrades with the pristine PLA as reference. More than the absolute values, the trend is important for the discussion. Also, in spite of these limitations, PS has been used as the standard for PLA in multiple previous studies 30-32. 2.5 Molecular Dynamics Simulation The molecular mechanisms responsible for the reduction in strength during degradation can be evaluated using Molecular Dynamics (MD) simulations. PLAFF3 force field proposed by McAliley and Bruce, 2011 33 was used to describe the bonded and non bonded interaction parameters of PLA. This forcefield was specifically developed for modelling PLA combining the CHARMM and OPLS force fields. The parameters of this forcefield were suitably adjusted by 8


Page 8 of 46

Page 9 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


the developers to reproduce experimentally observed melt density, crystal structure conformations, glass transition temperature (Tg) and volume expansion of PLA. PDLLA is amorphous in nature compared to PLLA and PDLA which are semi crystalline. It has been demonstrated that the forcefield used in the study PLAFF3 is better suited than its predecessors (PLAFF and PLAFF2) 34, 35 for modelling the amorphous dihedral angle distributions in PLA. PLAFF3 also fits the glass transition temperature of PLA with far more accuracy compared to its predecessors. Thus, among the available force fields PLAFF3 was found to be the best suited force field for PDLLA33. However, it should be noted that PLAFF3 does not take into account the stereo isomeric properties of PLA. CHARMM force field was adopted for defining the interaction parameters of HAp nanoparticles 36-37

and TIP3P water model was used for water molecules 38. All parameters used for various

models and the corresponding force field equations are provided in the Supporting Information (SI2.1). 2.5.1) Model Building and Simulation details First set consists of 5 unsolvated systems of varying monomer lengths of PLA. i.e. 25M-400C, 50M-200C, 100M-100C, 200M-50C and 1000M-20C where M stands for the number of monomers and C stands for the number of chains. The 1000M-20C system was considered as pristine PLA as the molecular weight of 1000 monomer chain (~72000 g/mol) is close to the range of the actual molecular weight of PLA used in the experiments (75000-120000 g/mol). Fully degraded PLA was simulated as the lowest monomer length (25M-400C) with 50% weight of water molecules. Thus, in the second set, for the varying degree of polymerization we incorporated varying degree of water saturation. ie. 1) 1000M-20C-0% water, 2) 200M-50C-5% water, 3) 100M-100C-10% water, 4) 50M-200C-20% water and 5) 25M-400C-50% water. In the 9



third set, the above pristine (unsolvated 1000M-20C-0% water) and fully degraded (solvated 25M-400C-50% water) PLA systems were incorporated with 5% weight of HAp nanoparticles. The initial configurations of all the systems were prepared using Packmol 39. A typical simulation box containing 25M-400C PLA with 50 % water and 5% HAp is shown in Figure 2. The system was minimized and then equilibrated in the NPT ensemble with 300K temperature and 1 atm pressure. A bulk density of 1.25 g/cc corresponding to the original density of PLA was ensured for all unsolvated systems by controlling the simulation box volume. At the end of equilibration, a deformation at the rate of 0.02% of original box length per 10-15 second was applied along Z-axis. The box was subjected to a maximum strain of 100%. Stress was calculated as the negative of total pressure along the direction of strain. The stress-strain relationship was plotted and Young’s modulus (E) was determined as the slope of the initial linear portion of the curve. There is an alternative method to perform deformation using step-wise NVT dynamics. In this method, the system is strained using displacement control. After every step of strain, the system is equilibrated in NVT dynamics. The method is generally used in problems in which the state of the system at each percentage strain is of interest to the observer. For example, a coupled diffusion-deformation problem in which water dynamics within a strained polymer matrix and the alterations it creates in the free volume is of interest. However, since our focus is primarily the stress-strain relationship and not the state of the system at different percentage strain, the first method of NPT dynamics is adopted in this study. All simulations were repeated five times for five different initial configurations of PLA-HApwater. The step by step simulation details, including energy minimization, equilibration and production/deformation are provided in Supporting Information (SI2.2). 10


Page 10 of 46

Page 11 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Two additional set of simulations are also performed in order to confirm some of the observations. In the first set the degree of polymerization is varied maintaining the percentage of water constant (5%). Four systems are obtained in this set ie. 1) 200M-50C-5% water, 100M100C-5% water, 3) 50M-200C-5% water and 4) 25M-400C-5% water. In the second set the degree of polymerization is fixed (100M-100C) and the water saturation is varied. Five systems are obtained in this set ie. 1) 100M-100C-0% water, 100M-100C-5% water, 100M-100C-15% water and 100M-100C-20% water. The results of these simulations are provided in Supporting Information (SI6).

Figure 2: A typical molecular model of PLA/HAp with water molecules. All simulations were performed using Large-Scale Atomic Molecular Massively Parallel Simulator (LAMMPS)40. Visualisation and trajectory analysis were carried out using Visual Molecular Dynamics (VMD) 41.

11



3. Results The degrading PLA films are often brittle and thus unsuitable for standard testing procedures such as a uniaxial tensile test for determining its mechanical properties. Nanomechanical testing techniques such as nanoindentation and nanoDMA not only facilitates indentation on in-vitro degraded samples but also enables to quantify the spatial heterogeneity in mechanical properties of nanocomposites (PLA/HAp). Quasi-static nanoindentation determines Young’s modulus (E) and Hardness (H) of purely elastic and viscoelastic materials at the nanoscale. However, for rubbery polymers such as PLA, quasi-static nanoindentation is not suitable due to the larger viscous component. When the material strain is non-synchronous with the applied stress, there is a time lag between the loading and deformation response. During nanoindentation of polymeric materials, this time lag often results in a persisting deformation during a hold period as the load is kept constant. During unloading, this leads to a nose in the initial part of the unloading curve which in extreme cases results in a negative stiffness 27-29. The effect can be controlled by varying the loading rate and holding time. However, for a highly viscoelastic material such as PLA, it was observed that the nose effect persists even after a very slow loading and a prolonged holding. It was thus determined that quasi-static indentation is not a suitable method to determine the elastic modulus (E) and hardness (H) of pristine PLA and PLA/HAp nanocomposite. Alternatively, dynamic nanoindentation is employed to determine the storage modulus, loss modulus and tan δ of the system. 3.1) Dynamic Nanoindentation Figure 3 shows the variation of dynamic properties such as storage modulus and tan δ of PLA and PLA/5HAp over a period of 0-55 days from the point of casting. A similar variation of 12


Page 12 of 46

Page 13 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


hardness and loss modulus is provided in Supporting Information (SI3). The storage modulus and hardness quantify the elastic response of a material and loss modulus and tan δ quantify the viscous response of a material over a period in which the material undergoes degradation. Tan δ is computed as the ratio of storage modulus to loss modulus. The properties are quantified at different frequencies ranging from 51.5 to 201.5 Hz during dynamic nanoindentation. The representative values at 51.5 Hz, 125 Hz, and 201.5 Hz are reported here. The storage modulus, loss modulus, and tan δ does not show significant dependence on the frequency with the variability in values less than 15% in most of the cases. However, few points exhibit a larger variability. For instance, storage modulus values on the 55th day in pure PLA (Figure 3) exhibits a positive correlation with frequency. This can be explained by the load rate dependence of elastic modulus. At higher frequencies, elastic properties are often overestimated and viscous properties are underestimated due to lower response time. It is observed that such frequency dependent response is predominant at the later stages of degradation. All properties are reported from the lower range of frequency (51.5 Hz) and considered as the representative value henceforth. Addition of nanoparticles (HAp in this study) enhances the mechanical properties of pristine PLA matrix. As determined, storage modulus is found to vary from 1-3 GPa for pristine PLA and from 2-6 GPa for PLA/5HAp nanocomposite. Over the period of 0 to 55 days, the storage modulus of PLA is observed to increase during the initial stages (up to 10-25 days). This increase in strength can be attributed to the realignment of polymer chains within the matrix during the initial period and the slowly increasing level of water saturation. The mechanism responsible for this initial increase is discussed in detail in subsequent section. Following this initial increase, around 25-35 days, the mechanical properties start to decrease. This point can be considered as the onset of degradation. 13



Figure 3: Frequency dependence of storage modulus and tan δ values for (a, c) PLA and (b, d) PLA/5HAp over a period of 0-55 days The detailed frequency sweep data of storage modulus for pure PLA and 1%, 5% and 10% HApPLA nanocomposite over a period of 0 to 55 days is provided in the Supporting Information (SI4). It is observed that for pure PLA, the maximum value of storage modulus, averaging around 3 GPa, is obtained on the 10th day after which the value reduces. For 5% HAp, maximum value of approximately 4-6 GPa is observed on the 25th day. This possibly indicates that the onset of degradation and subsequent reduction in mechanical properties are faster in pure PLA compared to PLA/HAp nanocomposite. This shift could be due to the hydrophilic nature of the HAp nanoparticles. When water molecules cluster around the nanoparticles they disrupt the 14


Page 14 of 46

Page 15 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


interaction between polymer and HAp. In addition it could also mean that more water is attracted to HAp, less water is available to interact with the polymer triggering hydrolytic degradation. The storage modulus of nanocomposite system on the 25th day is almost twice that of the pristine polymer. However, as the polymer degrades (55th day) the storage modulus (~0.7 GPa) and hardness (~0.002 GPa) values become comparable for both the pristine and nanocomposite systems. This indicates that during degradation the influence of nanoparticle reduces and subsequently becomes negligible in the degraded state and thus they no longer contribute to storage modulus of polymer matrix. However, for tan δ, loss modulus or creep displacement, a similar trend is not observed. At the beginning of curing process (0th day), tan δ is greater than 1 as the material exhibits high viscous behavior. Over the curing period, this value reduces and becomes constant between 1035 days. As degradation sets in for pure PLA, tan δ rises to gel point, where the value of storage modulus is equal to that of loss modulus, on the 55th day. In case of PLA/5HAp, the tan δ value reduces initially (0-10 days) and then remains constant for up to 55 days without further increase. These observations suggest that the initiation of drop in mechanical properties due to degradation is delayed in the nanocomposite reinforced systems. In all the experimental observations, the general trend of initial increase and eventual decrease in storage modulus is sustained. Similarly the initial decrease and subsequent increase in tan δ is also constant. Nevertheless it should be noted that the frequency of the tests varies between 5-10 days in these experiments. Thus, it is extremely difficult to determine the exact point of onset of degradation from the time dependent behaviour of storage modulus, loss modulus and tan δ values obtained in this study. However, we can still infer a broader range of time at which the reduction in mechanical properties is initiated.

15



3.2) Fourier Transform Infrared (FTIR) Spectroscopy The FTIR spectra of samples stored under high humidity conditions for accelerated degradation is shown in Figure 4. RH maintained greater than 95% provides excess water to the polymer matrix for hydrolysis as well as for solvation. A broad peak at 3387 cm-1 corresponding to O-H stretching vibrations is observed in the spectra for 20 and 30 days old sample whereas it is absent until 10th day. This peak indicates that the PLA under high humidity has possibly undergone extensive hydrolysis by the 20th day. It is reported that for hydrolysis, it is necessary to have enough free water in the matrix 4.

Figure 4: ATR spectrum of PLA maintained under high humidity conditions over a period of 0 to 30 days The sharp peak at 1747 cm-1 corresponds to C=O carbonyl stretch and 1082 cm-1 correspond to C-O-C stretch. The peaks at 2944-2994 cm-1 corresponds to C-H stretch. The peak around 750 cm-1 corresponds to –C=O of terminal -COOH (carboxylic acid).

16


Page 16 of 46

Page 17 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


3.3) Gel Permeation Chromatography (GPC) The variation in the distribution of molecular weight observed in GPC over time is shown in Figure 5. It is observed that the molecular weight continuously decreases over the period of 0-30 days. The spread of molecular weights represented by the standard deviation is also observed to reduce over time. Thus as degradation proceeds, the chains become more and more uniformly sized. It is observed that for pristine PLA the average molecular weight is 60000 g/mol. On the 30th day, this average value has halved to 30000 g/mol. Samples preserved under high humidity shows faster degradation consistently as the hydrolysis triggered by the presence of water is critical in controlling the rate of degradation.

Figure 5: Distribution of molecular weight of PLA maintained under normal and high humidity conditions obtained over a period of 0 to 30 days 3.4) Molecular Dynamics Simulations In this study, we consider five unsolvated systems, as discussed in the methodology, of approximately same size and density (1.25g/cc), however, with varying chain lengths. These models represent different stages of degradation due to random scission. It is observed that 17



between these systems there is no significant difference in a stress-strain relationship or Young’s modulus (E) value as indicated by Figure 6. The possible reason for this observation is discussed in the subsequent section.

Figure 6: Comparison of Young’s Modulus (E) in PLA of varying chain length and unsolvated and solvated system. The second set of simulations was performed on the same 5 unsolvated PLA systems by incorporating the varying degrees of water saturation from 0% to 50% as shown in Figure 6. It is reported that in PDLLA the degree of saturation rises from 1% to 40% within a period of 10 to 40 days 32. Thus the highest level of saturation was chosen to be 50%. It is observed that there is a significant lowering of maximum stress and Young’s modulus in this solvated system (2.86 േ 0.09 GPa) compared to the non-degraded (unsolvated) system (4.28 േ 0.13 GPa) as shown in Figure 6. For varying water saturation, the Young’s Modulus initially increases (0%-5%) and 18


Page 18 of 46

Page 19 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


then starts decreasing (5% to 50%). This is analogous to our observations from the nanoDMA estimation of storage modulus where the mechanical properties initially increases and then subsequently reduces (Figure 3). The third set of systems considered for the molecular dynamics study are the pristine (1000M20C-0% water) and degraded (25M-400C-50% water) PLA with and without 5% HAp nanoparticles. It is reported previously 2, 10, 26, 42 that presence of nanoparticles enhances the mechanical properties of the polymeric system. However, it is also observed from nanoDMA that the degraded PLA/HAp system shows minimal enhancement in mechanical properties (2.99 േ 0.19 GPa). Nevertheless, compared to a pristine system, the 5% HAp reinforced PLA exhibits a higher mechanical strength of 4.62 േ 0.14 GPa. Thus, it is observed that in a degraded system, the presence of HAp nanoparticles has negligible influence in enhancing the mechanical strength. The stress-strain plots of all the systems mentioned in this section are provided in the Supporting Information (SI5). 4. Discussion The combination of experimental and nanomechanical investigation studies as described in the previous sections provides insights into the degradation behavior of PLA and PLA/HAp nanocomposites. In this section, we attempt to correlate these observations and explain the mechanism leading to the loss in mechanical property over time as observed in Figure 3. Molecular dynamics simulations are applied to investigate this mechanistic study. The degradation of a polymer at an atomistic length scale can be attributed to two major factors: a) break down or scission of polymer chains to smaller oligomeric units due to hydrolysis and b) presence of excess water (solvation) between polymer chains, altering the load transfer mechanism of the polymer matrix. 19



Experimentally it is difficult to decouple these two contributing factors as they occur simultaneously, one affecting the other. However, through molecular dynamics simulations, we observe the independent role of scission and solvation in the reduction of mechanical properties. Degradation of PLA leads to the scission of polymer chains as external water attacks the ester group (-COO) and breaks it down to an acid (-COOH) and alcohol (-OH) terminated residue as shown in Figure 7. The ester group of any Nth monomer can be hydrolysed during this scission. The two extreme cases are a) scission of the terminal monomer (monomer M1 in Figure 7), which reduces the original length N to N-1 number of monomers, leaving most of the chain intact or b) a random scission which can occur at any point in the length of the chain (monomer M2 in Figure 7). A single scission at the middle of the chain has a greater impact than many terminal scissions as the former reduces the molecular weight significantly. Hence it is assumed that random scissions control the molecular weight reduction and subsequently the degradation 46

. It is also observed from GPC experiments in Figure 5 that degradation leads to an increasingly

uniform distribution of molecular weights. Pristine PLA has an average molecular weight of 60,000g/mol. In the same matrix, there are longer chains whose molecular weight goes up to 130,000 g/mol. However, by the 30th day, almost all the longer chains have broken down into smaller units with molecular weight averaging at 30,000 g/mol and the longest chains weighing 50,000 g/mol. It is to be noted that these values are qualitative as explained in the methodology section. Thus, it can be assumed that the degraded state of PLA can be represented by short and uniformly sized polymeric chains. This is an assumption adopted in building our molecular models for simulation study. The extreme case of 25M-400C with 50% water is used as the degraded system and compared with the non-degraded state of 1000M-20C-0%water.

20


Page 20 of 46

Page 21 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


It is interesting to note that according to the GPC experiment, by the 30th day most of the larger polymer chains are broken down into smaller oligomeric units. However, the significant reduction in mechanical properties is not observed until the 55th day (Figure 3). This time lag between molecular weight reduction and lowering of mechanical properties has been observed previously with poly (lactic-co-glycolic acid) (PGLA) 16 as well. The authors of that work have justified this lag in PGLA system by pointing out that, even when the molecular weight has significantly reduced, there are still longer chains in the matrix capable of load transfer. However, this is not the case in this PLA system as both the average molecular weight as well as the distribution has significantly reduced. These reductions are expected to affect the mechanical properties. The origin of elastic strength at the molecular scale can be attributed to the inherent chain elasticity, entanglement and physical interactions between polymeric chains 43-44. As polymeric chains break down into smaller units, the contribution from physical crosslinks and entanglement are expected to reduce. However, the other contributing factors such as chain elasticity and physical interactions (electrostatic and van der Waals) between functional groups remain intact between the polymer chains. Shorter chains may also be able to lead to a more compact packing leaving an altered configuration of free volume in a polymeric system. Overall, these could compensate for the reduction in mechanical properties caused by loss of entanglement. Evidence of such compensating effect is observed from our molecular dynamics investigations. Figure 6 shows that all other parameters such as density remaining constant, the stress-strain behavior and elastic modulus of PLA with varying oligomeric units remained similar. However, this cannot be generalized and is highly dependent on the specific functional groups and interaction behavior in different polymeric systems.

21



The second cause for the loss or reduction in mechanical properties is the presence of water. In our system, it is observed that the presence of water molecules has more contribution towards the lowering of mechanical properties compared to the scission of chains. From FTIR study, it is observed that the concentration of water within the matrix is significant from 20th to 30th day for samples preserved under high humidity (Figure 4). In normal humidity conditions, significant adsorption of water molecules and their accumulation in the polymer matrix is further delayed. This delay in the adsorption sufficient water into the polymer matrix from the atmosphere, is one of the reasons for the delay in the reduction of mechanical properties. Some of this water aids in the hydrolysis and breaking down of chains, whereas, others remain within the matrix interacting with the polymer chains (Figure 7). It is this free water available in the matrix that contributes towards the reduction in mechanical properties. This reduction is similar to the behavior of hydrogels, with high water absorption capacity. The mechanical properties of these hydrogels are dependent on the percentage of water absorbed. Free water in hydrogels form crosslinks or water bridges between distant locations of hydrophilic groups 45-47. The length of these water-bridges varies depending on the saturation i.e. the availability of water as well as the expansion of free volume to accommodate these molecules within the polymer matrix.

22


Page 22 of 46

Page 23 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 7: Schematic representing non-degraded and degraded PLA. The mechanism of hydrolysis and solvation leading to the formation of water-bridges is depicted with the snapshot of water-bridge that forms between two polymer chains from the MD simulation Mechanism of load transfer is different for short vs long water-bridges (Figure 7). In the work of Xianfeng et. al. it was observed that the average size of water clusters increases as water content increases 32. Hence, shorter bridges are predominant at lower water content as opposed to longer bridges at higher water content. The shorter water-bridges between the polymeric chains can facilitate the load transfer by creating a physical crosslink between chains. These shorter water 23



bridges are responsible for the initial increase in mechanical properties at lower water content. However, as water content increases longer water-bridges are formed, connecting the interaction sites between polymeric chains. Water molecules also form solvation shells around terminal groups. These longer bridges and solvation shells are incapable of load transfer. Rather, they form multiple slip planes, perpendicular to the direction of the water bridges, which allow translational motion of water molecules relative to each other. This results in weak attractive forces among water molecules which are away from the reactive site of the polymer chain. This mechanism of multiple slip planes is similar to the larger number of degrees of freedom in the case of a long column as opposed to short strut in continuum mechanics. Thus the longer bridges are more susceptible to failure under tension and shear. Therefore, water molecules hinder the load transfer, subsequently reducing the stress carrying capacity of the polymeric chains. This results in further reduction of mechanical properties. Although chain scission is not found to contribute directly to mechanical property reduction via conventional mechanisms (entanglement and physical interactions), a coupled phenomenon of scission and solvation is observed in the degraded MD model (25M-400C-50% water). Shorter chains in this system lead to a larger number of terminal atoms. They in turn provide a larger number of interaction sites for water molecules to form solvation shells. For example, two major types of oxygen atoms in the PLA polymer chain have significant interaction with water molecules as observed from the radial distribution function (RDF). As shown in Figure 8, the two oxygen atoms in the acid terminated residue i.e. O3 and O4 strongly interact with the Oxygen atom (O) of the water molecule. It is interesting to note that these oxygen atoms are part of the terminal group. The corresponding oxygen atoms (O1 and O2) of the ester group (-COO-) within the chain does not exhibit such strong correlation with water molecules. Thus, the 24


Page 24 of 46

Page 25 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


alternate coupled mechanism of scission and solvation in degraded PLA contributes to the lowering of mechanical properties.

Figure 8: Radial Distribution Function (RDF) between the acid terminated residue in PLA polymer chain and water molecules Hydrophilic nanocomposite such as HAp is used in many structural applications where enhanced mechanical properties of PLA are desirable. However, the hydrophilic nature of these nanoparticles makes them susceptible to water interactions during degradation. In pristine PLA, the higher surface energy and surface to volume ratio of HAp nanoparticles leads to larger interaction with polymer chains. The chains at the proximity of nanoparticle get influenced due to site specific interactions with HAp. The free volumes close to these interaction sites are altered due to denser packing of polymer chains. Such region within the polymer matrix where the influence of nanoparticles alters the physical or mechanical properties of the polymer is defined as the influence zone of the nanoparticle. The site specific elastic modulus ‘E’ of the nanocomposite system is found to be a function of ‘r’ where ‘r’ is the distance from the nanoparticle 42 i.e. E=f(r). The value of E reduces radially outward from the polymer25



nanoparticle boundary. Regions outside this zone exhibit the elastic modulus of the pristine polymer. It is observed that, before the initiation of degradation, spatial heterogeneity in mechanical properties of nanocomposites results in the larger standard deviation of storage modulus values (0th day in Figure 9). In pristine PLA, sites of degradation are non-uniformly distributed due to localized scissions of polymer chains and non-uniform water absorption leading to spatial heterogeneity in mechanical properties. This is also evident from a larger standard deviation observed in measured mechanical properties of pristine PLA on initiation of degradation. The storage modulus on the 55th day for both PLA and PLA/HAp nanocomposite are comparable suggesting that during degradation the functional relationship between ‘E’ and ‘r’ are significantly altered. This can be substantiated by the molecular mechanism study of the pristine and degraded system with HAp. It is observed that the oxygen atom (OI) from the phosphate group (PO4) in HAp has strong interactions with the oxygen (O5) in the alcohol terminated residue (-CH(CH3)-OH) in pristine PLA (1000M-20C-5%HAp) as shown by the Radial Distribution Function (RDF) depicted in Figure 10. Similarly, the oxygen (Oh) from the OH ion in HAp has a strong correlation with the single bonded oxygen (O3) from the acid terminated residue (-COOH) of PLA. However, in the degraded system (25M-400C-50% water 5%HAp), these strong correlations are strongly interrupted by the ingress of water. The reactive sites of HAp, as well as PLA, are occupied by water molecules preventing development of necessary polymer-HAp interactions for load transfer. Thus, it is observed that, in PLA and PLA/HAp nanocomposite, site specific interaction of water molecules play a major role in the reduction of mechanical properties. Water molecules form solvation shells around the terminal acid (-COOH) and alcohol (-CH3-OH) group. Ester (-COO-) groups within the polymer chains provide sites to form water bridges between polymer chains. The load transfer mechanism is altered depending on the size of these water bridges. The effect 26


Page 26 of 46

Page 27 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


of chain scission and the resultant loss in entanglement is not as significant as the effect of solvation in the reduction of mechanical properties.

Figure 9: Comparison of storage modulus values obtained from dynamic nanoindentation for PLA and PLA/5HAP nanocomposite over a period of 0 to 55 days measured at a frequency of 51.5 Hz.

Figure 10: Radial Distribution Function (RDF) between -OH species in acid and alcohol terminated residue of PLA with HAp 27



5. Conclusion This work applies a combined experimental and molecular simulation approach to investigate the degradation of PLA and evaluate the relative role of solvation and scission in the reduction of mechanical properties. Dynamic nanoindentation (nanoDMA) is found to be particularly convenient to monitor the reduction and the spatial heterogeneity of mechanical properties (storage and loss modulus) in degrading polymers that exhibit high viscoelasticity. Degradation of PLA and PLA/HAp nanocomposite was investigated in this work and the reduction in mechanical properties measured over a period of two months. As the polymer is exposed to atmosphere, water molecules ingress into the matrix causing a) hydrolysis which leads to chain scission and b) site specific interactions between water and acid terminated residue (-COOH) leading to solvation. The combined effect of solvation and scission is responsible for the degradation. The molecular simulations revealed that the stress-strain relationship and elastic modulus of different systems of PLA, with varying chain length, remained constant. On the other hand, the representative degraded state of PLA (25M-400C), solvated by 50% weight of water exhibited significant reduction in mechanical properties. These observations reveal that solvation has a prominent role in the reduction of mechanical property compared to chain scission. The nanocomposite system at the initial days after casting exhibits higher mechanical properties compared to pristine PLA as expected from the reinforcing effect of nanoparticles. However, following the onset of degradation, both systems behave similar in terms of elastic properties. This reduction is attributed to the presence of water molecules between PLA and HAp which significantly reduces the influence zone of HAp as evidenced by molecular simulations. Supporting Information SI1. Principle and property estimation from dynamic nanoindentation SI2.1 Forcefield Parameters 28


Page 28 of 46

Page 29 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


SI2.2 Minimization, Equilibration and Deformation SI3. Variation of Hardness and Loss Modulus values for PLA and PLA/5HAP nanocomposite over a period of 0-55 days. SI4. Frequency sweep data of storage modulus for pure PLA and 1%, 5% and 10% HAp-PLA nanocomposite over a period of 0 to 55 days SI5. Summary of molecular dynamic simulations and estimation of Young’s modulus from the stress strain plot SI6. Additional Simulations Performed Acknowledgement Supercomputing facility used for simulations at PG Senapathy Centre for Computing Resource, Indian Institute of Technology, Madras is greatly acknowledged. 6. Reference 1. Auras, R.; Lim, L. T.; Selke, S. E. M.; Tsuji, H. Poly (Lactic Acid): Synthesis, Structures, Properties, Processing, and Applications, Second Ed; Wiley: New Jersey, 2010. 2. Lin, P. L.; Fang, H. W.; Tseng, T.; Lee, W. H. Effects of Hydroxyapatite Dosage on Mechanical and Biological Behaviors of Polylactic Acid Composite Materials. Mater. Lett. 2007, 61, 30093013. 3. Sodergard, A.; Stolt, M.; Properties of Lactic Acid Based Polymers and their Correlation with Composition, Prog. Polym. Sci. 2002, 27, 1123-1163. 4. Gleadall, A. Modelling Degradation of Biodegradable Polymers and their Mechanical Properties: Doctoral Dissertation. University of Leicester, 2015. 5. Gleadall, A.; Pan, J.; Kruft, M. A.; Kellomäki, M. Degradation Mechanisms of Bioresorbable Polyesters. Part 1. Effects of Random Scission, End Scission and Autocatalysis. Acta Biomater. 2014, 10, 2223-2232. 29



6. Gleadall, A.; Pan, J.; Kruft, M. A.; Kellomäki, M. Degradation Mechanisms of Bioresorbable Polyesters. Part 2. Effects of Initial Molecular Weight and Residual Monomer. Acta Biomater. 2014, 10, 2233-2240. 7. Navarro, M.; Ginebra, M. P.; Planell, J. A.; Barrias, C. C.; Barbosa, M. A. In Vitro Degradation Behavior of a Novel Bioresorbable Composite Material Based on PLA and a Soluble CaP Glass. Acta Biomater. 2005, 1, 411-419. 8. Raquez, J. M.; Habibi, Y.; Murariu, M.; Dubois, P. Polylactide (PLA)-Based Nanocomposites. Prog. Polym. Sci. 2013, 38, 1504-1542. 9. Migliaresi, C.; Fambri, L.; Cohn, D. A Study on the In Vitro Degradation of Poly(Lactic Acid). J. Biomater. Sci. Polym. 1994, 5, 591-606. 10. Russias, J.; Saiz, E.; Nalla, R. K.; Gryn, K.; Ritchie, R. O.; Tomsia, A. P. Fabrication and Mechanical Properties of PLA/HA Composites: A Study of In Vitro Degradation. Mater. Sci. Eng. C Biomim. Supramol. Syst. 2006, 26, 1289-1295. 11. Naik, A.; Best, S. M.; Cameron, R. E. The Influence of Silanisation on the Mechanical and Degradation Behaviour of PLGA/HA Composites. Mater. Sci. Eng. C 2015, 48, 642-650. 12. Butt, M. S.; Bai, J.; Wan, X.; Chu, C.; Xue, F.; Ding, H.; Zhou, G. Mechanical and Degradation Properties of Biodegradable Mg Strengthened Poly-Lactic Acid Composite through Plastic Injection Molding. Mater. Sci. Eng. C 2017, 70, 141-147. 13. Chantawansri, T. L.; Sirk, T. W.; Mrozek, R.; Lenhart, J. L.; Kröger, M.; Sliozberg, Y. R. The Effect of Polymer Chain Length on the Mechanical Properties of Triblock Copolymer Gels. Chem. Phys. Lett. 2014, 612, 157–161. 14. Al-Nasassrah, M. A.; Podczeck, F.; Newton, J. M. The Effect of an Increase in Chain Length on the Mechanical Properties of Polyethylene Glycols. Eur. J. Pharm. Biopharm. 1998, 46, 31–38.

30


Page 30 of 46

Page 31 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


15. Fetters, L. J.; Lohse, D. J.; Richter, D.; Witten, T. A. Zirkelt, A. Connection Between Polymer Molecular Weight, Density, Chain Dimensions, and Melt Viscoelastic Properties. Macromolecules 1994, 27, 4639-4647. 16. Shirazi, R. N.; Aldabbagh, F.; Erxleben, A.; Rochev, Y.; McHugh, P. Nanomechanical Properties of Poly(Lactic-Co-Glycolic) Acid Film during Degradation. Acta Biomater. 2014, 10, 4695–4703. 17. Li, Y.; Xin, S.; Bian, Y.; Dong, Q.; Han, C.; Xu, K.; Dong, L. Stereocomplex Crystallite Network in Poly(D,L-Lactide): Formation, Structure and the Effect on Shape Memory Behaviors and Enzymatic Hydrolysis of Poly(D,L-Lactide). RSC Adv. 2015, 5, 24352–24362. 18. Sarasua, J. R.; Zuza, E.; Imaz, N.; Meaurio, E. Crystallinity and Crystalline Confinement of the Amorphous Phase in Polylactides. Macromol. Symp. 2008, 272, 81–86. 19. Metters, A. T.; Bowman, C. N.; Anseth, K. S. A Statistical Kinetic Model for the Bulk Degradation of PLA-b-PEG-b-PLA Hydrogel Networks. J. Phys. Chem. B 2000, 104, 70437049. 20. Metters, A. T.; Bowman, C. N.; Anseth, K. S. A Statistical Kinetic Model for the Bulk Degradation of PLA-b-PEG-b-PLA Hydrogel Networks: Incorporating Network NonIdealities. J. Phys. Chem. B 2001, 105, 8069-8076. 21. Yoshikawa, M.; Goshi, Y.; Yamada, S.; Koga, N. Multistep Kinetic Behavior in the Thermal Degradation of Poly (L-Lactic Acid): A Physico-Geometrical Kinetic Interpretation. J. Phys. Chem. B 2014, 118, 11397-11405. 22. Dhakal, H. N.; Zhang, Z. Y.; Richardson, M. O. W. Effect of Water Absorption on the Mechanical Properties of Hemp Fibre Reinforced Unsaturated Polyester Composites. Compos. Sci. Technol. 2007, 67, 1674–1683.

31



23. Tibbitt, M. W.; Kloxin, A. M.; Sawicki, L. A.; Anseth, K. S. Mechanical Properties and Degradation of Chain and Step-Polymerized Photodegradable Hydrogels. Macromolecules 2013, 46, 2785–2792. 24. Saharudin, M. S.; Atif, R.; Shyha, I.; Inam, F. The Degradation of Mechanical Properties in Polymer Nano-Composites Exposed to Liquid Media – A Review. RSC Adv. 2016, 6, 1076– 1089. 25. Zheng, X.; Zhou, S.; Li, X.; Weng, J. Shape Memory Properties of Poly(D,LLactide)/Hydroxyapatite Composites. Biomaterials 2006, 27, 4288–4295. 26. Hong, Z.; Zhang, P.; He, C.; Qiu, X.; Liu, A.; Chen, L.; Chen, X.; Jing, X. Nano-Composite of Poly(L-Lactide) and Surface Grafted Hydroxyapatite: Mechanical Properties and Biocompatibility. Biomaterials 2005, 26, 6296–6304. 27. Herbert, E. G.; Oliver, W. C.; Pharr, G. M. Nanoindentation and the Dynamic Characterization of Viscoelastic Solids. J. Phys. D. Appl. Phys. 2008, 41, 074021. 28. Zhang, Y. F.; Bai, S. L.; Li, X. K.; Zhang, Z. Viscoelastic Properties of Nanosilica-Filled Epoxy Composites Investigated by Dynamic Nanoindentation. J. Polym. Sci. Part B Polym. Phys. 2009, 47, 1030–1038. 29. Hayes, S. A.; Goruppa, A. A.; Jones, F. R. Dynamic Nanoindentation as a Tool for the Examination of Polymeric Materials. J. Mater. Res. 2004, 19, 3298–3306. 30. Rathi, S. R.; Coughlin, E. B.; Hsu, S. L.; Golub, C. S.; Ling, G. H.; Tzivanis, M. J. Maintaining Structural Stability of Poly (Lactic Acid): Effects of Multifunctional Epoxy Based Reactive Oligomers. Polym. 2014, 6, 1232-1250. 31. Ghalia, M. A.; Dahman, Y. Investigating the Effect of Multi-functional Chain Extenders on PLA/PEG Copolymer Properties. Int. J. Biol. Macromol. 2017, 95, 494-504.

32


Page 32 of 46

Page 33 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


32. Li, X.; Murthy, N. S.; Latour, R. A. Structure of Hydrated Poly (d, l-lactic acid) Studied with Xray Diffraction and Molecular Simulation Methods. Macromolecules. 2012, 45, 4896-4906. 33. McAliley, J. H.; Bruce, D. A. Development of Force Field Parameters for Molecular Simulation of Polylactide. J. Chem. Theory Comput. 2011, 7, 3756–3767. 34. McAliley, J. H. Development of Improved Torsional Potentials in Classical Force Field Descriptions of Poly (lactic acid: Doctoral Dissertation. Clemson University, 2009. 35. O’Brien, C. P. Quantum and molecular modeling of polylactide: Doctoral Dissertation. Clemson University, 2005. 36. Dubey, D. K. Molecular Mechanics of Tropocollagen-Hydroxyapatite Biomaterials: Doctoral Dissertation. Purdue University, 2012. 37. Lin, T. J. Force Field Parameters and Atomistic Surface Models for Hydroxyapatite and Analysis of Biomolecular Adsorption at Aqueous Interfaces: Doctoral Dissertation. The University of Akron, 2013. 38. Mark, P.; Nilsson, L. Structure and Dynamics of the TIP3P , SPC , and SPC/E Water Models at 298 K. J. Phys. Chem. A 2001, 105, 9954–9960. 39. Martínez, L.; Andrade, R.; Birgin, E. G.; Martínez, J. M. Packmol: A Package for Building Initial Configurations for Molecular Dynamics Simulations. J. Comput. Chem. 2009, 30, 21572164. 40. Plimpton, S. Fast Parallel Algorithms for Short-Range Molecular Dynamics. J. Comp. Phys. 1995, 117, 1-19. 41. Humphrey, W.; Dalke, A.; Schulten, K. VMD - Visual Molecular Dynamics. J. Molec. Graphics. 1996, 14, 33-38.

33



42. Rath, A.; Mathesan, S.; Ghosh, P. Nanomechanical Characterization and Molecular Mechanism Study of Nanoparticle Reinforced and Cross-Linked Chitosan Biopolymer. J. Mech. Behav. Biomed. Mater. 2016, 55, 42-52. 43. Heinrich, G.; Vilgis, T. A. Contribution of Entanglements to the Mechanical Properties of Carbon Black-Filled Polymer Networks. Macromolecules 1993, 26, 1109-1119. 44. Grijpma, D. W.; Penning, J. P.; Pennings, A. J. Chain Entanglement, Mechanical Properties and Drawability of Poly (Lactide). Colloid Polym. Sci. 1994, 272, 1068-1081. 45. Aquino, A. J.; Tunega, D.; Pasalic, H.; Schaumann, G. E.; Haberhauer, G.; Gerzabek, M. H.; Lischka, H. Molecular Dynamics Simulations of Water Molecule-Bridges in Polar Domains of Humic Acids. Crit. Rev. Environ. Sci. Technol. 2011, 45, 8411-8419. 46. Ghosh, P.; Katti, D. R.; Katti, K. S. Mineral Proximity Influences Mechanical Response of Proteins in Biological Mineral− Protein Hybrid Systems. Biomacromolecules 2007, 8, 851-856. 47. Vyavahare, O.; Ng, D.; Hsu, S. L. Analysis of Structural Rearrangements of Poly (Lactic Acid) in the Presence of Water. J. Phys. Chem. B 2014, 118, 4185-4193.

34


Page 34 of 46

Page 35 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


TOC Graphic

35



Figure 1: The frequency sweep loading used for Dynamic nanoindentation. The frequencies at which mechanical properties are plotted are chosen from the start, middle and end of the sweep. 84x50mm (300 x 300 DPI)


Page 36 of 46

Page 37 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 2: A typical molecular model of PLA/HAp with water molecules. All simulations were performed using Large-Scale Atomic Molecular Massively Parallel Simulator (LAMMPS)40. Visualisation and trajectory analysis were carried out using Visual Molecular Dynamics (VMD) 41. 114x71mm (300 x 300 DPI)



Figure 3: Frequency dependence of storage modulus and tan δ values for (a, c) PLA and (b, d) PLA/5HAp over a period of 0-55 days 171x131mm (300 x 300 DPI)


Page 38 of 46

Page 39 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 4: ATR spectrum of PLA maintained under high humidity conditions over a period of 0 to 30 days 164x70mm (300 x 300 DPI)



Figure 5: Distribution of molecular weight of PLA maintained under normal and high humidity conditions obtained over a period of 0 to 30 days 73x56mm (300 x 300 DPI)


Page 40 of 46

Page 41 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 6: Comparison of Young’s Modulus (E) in PLA of varying chain length and unsolvated and solvated system. 100x97mm (300 x 300 DPI)



Figure 7: Schematic representing non-degraded and degraded PLA. The mechanism of hydrolysis and solvation leading to the formation of water-bridges is depicted with the snapshot of water-bridge that forms between two polymer chains from the MD simulation 161x137mm (300 x 300 DPI)


Page 42 of 46

Page 43 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 8: Radial Distribution Function (RDF) between the acid terminated residue in PLA polymer chain and water molecules 98x76mm (300 x 300 DPI)



Figure 9: Comparison of storage modulus values obtained from dynamic nanoindentation for PLA and PLA/5HAP nanocomposite over a period of 0 to 55 days measured at a frequency of 51.5 Hz. 87x61mm (300 x 300 DPI)


Page 44 of 46

Page 45 of 46 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure 10: Radial Distribution Function (RDF) between -OH species in acid and alcohol terminated residue of PLA with HAp 149x63mm (300 x 300 DPI)



TOC Graphic 92x55mm (300 x 300 DPI)


Page 46 of 46

Comparative Role of Chain Scission and Solvation in the

Recommend Documents