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Fabricating and Characterizing Polymers for Biomedical Devices
Crystal An
Jessica Fan ([email protected])
Karen Gu
Sarbari Sarkar ([email protected])
Jake Walsh
Abstract
Throughout the past few decades’ worth of scientific progress, the use of engineered devices in the medical field has saved and improved numerous lives. Poly-l-Lactic Acid (PLLA), a polymer commonly used to build medical devices like sutures or stents, is an ideal material for such products because of its biodegradability, cost-effectiveness, and overall strength. In this project, PLLA was fabricated and tested in order to identify processes that would improve its properties for medical applications. The crystallization, glass transition, and melting temperatures of PLLA pellets were analyzed through a differential scanning calorimeter (DSC), after which PLLA fibers were fabricated through plunger extrusion. Primarily, this paper examines the process of drawing as a method of improving PLLA’s properties by increasing the homogeneity of its crystal orientation. Mechanical stress testing of the fibers shows that drawing increases the overall tensile strength of PLLA in the elastic, viscoelastic, and plastic deformation stages. This result was confirmed through X-ray diffraction, which showed that drawing fibers increased their degree of orientation and therefore their strength. Fibers that were drawn or had undergone the process of annealing were both shown to have greater crystallinity. While the effects of the annealing process can be further researched, this paper demonstrates that
drawing PLLA fibers strengthens them, enhancing their effectiveness as biomaterials.
1 Introduction Biomaterials science, an interdisciplinary field, combines knowledge from chemistry and biology to synthesize and modify different substances for various medical purposes. Physical and chemical properties are used to differentiate and understand potential usages of the newly made biomaterials, which in turn are used in medicine and surgery to improve the quality of human life. Used in a variety of biomedical devices, biomaterials are non-viable substances suitable for implantation in a living body to repair or replace damaged parts.1 Therefore, the characterization and modification of biomaterials to make them more useful in biomedical applications is of utmost importance. Bioplastics in particular are especially promising for use in biomedical devices because of their versatility: they have varied physical and chemical properties such as tensile strength, flexibility, and biodegradability. Furthermore, many are produced from renewable resources. In addition, they may be uniquely suited to biomedical applications due to their common nontoxicity in the human body.2 For this reason, the fabrication and characterization of bioplastic polymers constitute extremely
important tasks for the construction and design of biomaterials in general. Poly-l-lactic acid (PLLA), a biodegradable polymer broadly used in the biomedical industry, was extensively tested to investigate its material properties and potential applications. As PLLA lacks the prerequisite mechanical strength for some biomedical applications, such as sutures, vascular grafts, and nerve conduits, improving PLLA’s mechanical properties is critical to the field of biomaterials. In order to do this, differential scanning calorimetry (DSC) tests were conducted to determine certain basic properties of PLLA relevant to its processing, such as its melting point and glass transition temperature. Such data were then used to determine the temperatures at which to extrude, draw, and anneal PLLA. Finally, PLLA processed into fibers using these various methods was mechanically tested to determine which processing method best improved mechanical strength. In addition, x-ray diffraction (XRD) was used to characterize and correlate the crystal structure of PLLA to its physical properties to determine why certain processing methods result in stronger fibers. These results were analyzed in order to determine future applications for the polymer and its processing. 2 Background 2.1 Chemical Properties of Polymers
Composed of identical, repeating units called monomers, polymers are generally materials with high molecular weights. They can be found in nature or produced synthetically in laboratories, in which case they may be referred to as plastics. Polymerization, the process of chemically combining monomers to form polymers, can be accomplished by propagating a reaction through the addition of heat or free radicals, or by opening a ring in the molecular structure. These monomers eventually combine into long chains that may branch off multiple times.3
Polymers can be divided into one of two groups: thermoset or thermoplastic. This distinction is based on whether the monomers have crosslinking chains capable of bonding main chains together in a way that creates a three-dimensional structure.4 Thermoset polymers have such side chains that strengthen the overall molecule by creating bonds. However, these bonds are destroyed upon remelting, and thus thermoset polymers do not reform in a consistent manner. Though thermoplastic polymers have relatively less strength because they lack such crosslinking, they can reform with mostly similar properties after melting.
Furthermore, a polymer can solidify into several different states depending upon the manner in which it is made and processed. When it is heated into a melt and then allowed to cool slowly, a process known as annealing, it is more likely to form crystals. Polymers in crystal form have highly regular structures at the molecular level and exist at a state of relatively low entropy compensated for by the exothermic nature of crystallization.5 In particularly crystalline samples, the polymer chains may be chain-folded to form a highly ordered accordion-like structure. These chain folds can grow radially to form spherulites, or spherical grains. Alternatively, if the melt is quenched, or cooled very rapidly, crystals will have less time to form, and the polymer will have an amorphous structure. Amorphous polymers have little to no regularity in form; resultantly, such polymers can easily become entangled, a process that strengthens the polymer’s overall structure by facilitating the creation of intermolecular attractive forces.6 Most polymers contain a combination of both of these forms and are therefore semicrystalline. In fact, polymers typically have at most 80% crystallinity.7
In general, polymers can be manipulated with respect to a wide variety of characteristics, including solubility. Some polymers used to contain highly reactive solvents, like Teflon, are very resistant to chemical dissolution. On the other hand,
polymers can also be induced to easily degrade in various solvents, especially water. This property enables use in biomedical devices that need to dissolve once their purpose is served. 2.2 Physical Properties of Polymers
The length of the polymer chain, and thus the molecular weight, contributes to the melting and boiling temperatures of the polymer. Longer polymer chain lengths tend to increase melting and boiling temperatures, because more energy is required to disrupt the greater chain entanglement to separate polymers into liquids or gases; shorter lengths do the opposite. The state of polymers can also determine other physical properties. For example, crystalline polymers are more ordered and tend to be more dense than amorphous polymers.
Mechanical properties may be used to describe the behavior of a polymer under stress, which is defined as the force applied over a unit area.8 The least stress that a polymer can withstand before breaking is its tensile strength. A closely related characteristic is elongation-to-break, which is the strain on a sample at its breaking point. While tensile strength is the least amount of pressure required to break a polymer, elongation-to-break is the maximum distance to which a material can be stretched before mechanical failure. These properties may be used to distinguish polymers based on their respective stretching abilities for possible applications.
Stress may be plotted on the y-axis over strain on the x-axis, producing a stress-strain curve. The slope of the linear portion of a stress-strain curve is known as Young’s modulus, which represents the ratio of stress to strain on a polymer in its elastic stage in which deformation is fully recoverable. Rigid materials have high modulus values, while elastic materials have lower values because they require less stress to be elongated. After elastic deformation concludes, most non-ideal materials,
including PLLA, enter a stage of viscoelastic deformation. Unlike elastic deformation, which is entirely recoverable, viscoelastic deformation is only partially recoverable. Moreover, when a substance begins to viscoelastically deform, it will often begin to undergo creep, a process in which the strain on a material continues to increase regardless of whether more stress is exerted on it because of residual stresses exerted over a longer period of time. A material will remain in its viscoelastic stage until its yielding point, after which a material will deform plastically, or completely irrecoverably, until it reaches its failure point and breaks.
2.3 PLLA Polylactic acid is a polyester that is derived from renewable resources, such as corn starch and tapioca roots.9 It is the polymer form of the monomer lactic acid. There are two enantiomers of polylactic acid with different chemical properties: the D-form (PDLA) and the L-form (PLLA). PLLA, the synthesis of which can be seen in Figure 1, is the form that is most broadly used in commercial applications, both medical and otherwise.10 Furthermore, since PLLA degrades naturally in vivo in a period of 10 to 18 months, it is commonly used as a biomaterial for medical applications that require the gradual dissolution of a device within the body.11 PLLA can easily be processed through molding, extrusion, and other methods. Thus, it can be processed into many forms including fibers, films, and three-dimensional shapes created by 3-D printing and similar processes. This ease of processing, combined with its biodegradability and its renewability as a resource, makes PLLA a promising plastic for the future, both in consumer and in biomedical applications. 2.4 DSC Differential scanning calorimetry (DSC) measures the flow of heat into or out of a sample. It measures the loss or gain of
heat in a sample relative to a fixed reference point and heats it at a constant rate while plotting the data produced against the whole temperature range.12 In essence, the differential scanning calorimeter, shown in Figure 2, identifies the thermochemical properties of a sample, including its glass transition temperature, crystallization temperature, melting point, and specific heat capacity by putting it through a heat cycle. This cycling makes the sample more amorphous and is necessary to study the amorphous properties of the material if the sample is originally crystalline. By analyzing the change in heat flow at different temperatures, the calorimeter can be used to accurately determine the phase transitions of the material.13 Data from the DSC test can help to determine the temperature at which to extrude the polymer and the temperature at which to draw the fiber. In terms of this experiment, it is important to understand the behavior of the PLLA at various temperatures, particularly in typical human body temperatures, to determine whether it would be an effective material for biomedical devices. 2.5 Extrusion Polymer extrusion is carried out by an extruder, as seen in Figure 3, and is the process of melting the polymer and pushing it through a die in order to form uniform sheets, rods, or fibers. Many biomedical devices can be fabricated through extrusion. The profile of the extruded product depends on the shape of the die’s cross-section. Polymer material in the form of pellets is fed into an extruder through a hopper. The material is then conveyed forward by a feeding screw that constantly rotates at varying speeds during extrusion. The feeding screw goes into the barrel and forces the material through the die, converting it to a continuous polymer product. Meanwhile, heating elements placed over the four zones of the barrel soften and melt the polymer at different preset temperatures.14 The product going out of the die is cooled by blown air or a water bath. Before the extrusion process, the polymer may be mixed with
colorants.15 They may also be compounded with other materials, ultraviolet (UV) inhibitors, and additives during the process.16 Extrusion is a suitable method for polymers that are robust against heat, and results in an amorphous structure due to rapid cooling. Plunger extrusion, used in this experiment, pushes the polymer through the die using the pressure produced by the apparatus. It is considered to produce less waste material than the more common extrusion process, twin-screw extrusion.17 2.6 XRD X-ray diffraction (XRD) is a crucial analytical technique used to determine the crystalline structure and chemical composition of a substance. The X-ray diffractometer primarily consists of an X-ray tube, a platform for the sample, and an X-ray detector. It functions by emitting high energy X-ray light onto the sample and then determining the crystallinity of a substance by analyzing its diffraction pattern. XRD utilizes the scattered X-rays over a range of angles in order to determine the crystallographic characteristics and chemical composition.18 This technique can determine whether a material is amorphous or crystalline and whether the material is isotropic or anisotropic. In an isotropic material, the diffraction pattern is random, which means that it is the same in all directions. In an anisotropic material, the properties of the material vary with different crystallographic orientations. The degree of crystallinity can be determined by measuring the width of the peaks on the integrated graph of diffraction intensity; the narrower the peaks, the higher the degree of crystallinity.19 This technique also identifies the angle of diffraction, which can then be used to determine the crystalline structure through Bragg’s Law. In conjunction with Bragg’s Law, it is possible to determine the degree of crystallinity and contrast between different sections of the sample.20 From the XRD data, the preferred orientation of the sample can also be determined. The accompanying software allows for the elimination of background noise from the air
as well as amorphous data from the polymer itself in order to better identify the crystalline structure, as can be seen in Figure 4.21 Thus, many characteristics of the structure of various materials can be studied through the process of X-ray diffraction and the subsequent analysis of interference patterns. 2.7 Bragg’s Law Specifically, X-ray diffractometers utilize Bragg’s law, which describes the wavelengths at which light elastically scatters from a crystal lattice depending on both the distances between the lattice’s layers and the angle at which the light impacts the crystal.22 For this purpose, the equation 2𝑑 sin 𝜃 = 𝑛𝜆 is utilized, in which d is the separation between crystal lattice layers, is the scattering angle, n is an integer, and λ is the wavelength of incident light.23 Bragg’s law essentially states that if the separations of periodic layers in a crystal lattice are equal to an integer multiple of the incident light’s wavelength, then constructive interference will occur, amplifying the wavelength of the scattered light. As such, X-ray diffractometers can be used to gain considerable insight into the internal semicrystalline structures of polymers by observing the wavelengths of scattered light of different intensities at varying angles. This orderly constructive interference allows for the determination of either interatomic or intermolecular distances through the creation of a diffraction pattern. Plotting the intensity of the diffracted light over the scattering angle yields characteristic peaks depending on the substance analyzed. Since narrow peaks correspond to high levels of crystallinity, Bragg’s law can also be used to calculate a sample’s relative crystallinity. 3 Experimental Design 3.1 DSC
An 8.94 mg sample of PLLA was first measured using a milligram balance, then prepared for analysis by a differential
scanning calorimeter, specifically, the Mettler Toledo TS0801R0. The sample was then placed in the calorimeter, which had been programmed specifically for this experiment. The program put the sample through a cycle of heating, cooling, reheating, and then a final cooling stage over a period of 92 minutes through a temperature range from 25°C to 300°C. The rate of temperature change was programmed to 10°C/minute for both of the heating cycles, -10°C/minute for the first cooling cycle, and -50°C/minute for the second cooling cycle. The sample was heated from 25°C to 300°C, maintained at an isothermal stage of 300°C lasting for 2 minutes, cooled from 300°C to 25°C, maintained at another isothermal stage of 25°C lasting for 2 minutes, reheated from 25°C to 300°C, and finally rapidly cooled from 300°C to an ambient temperature of 25°C. Through this experiment, the glass transition temperature, crystallization temperature, and melting temperature were identified to assist in further processing of PLLA. 3.2 Fabricating Fibers (Extrusion)
PLLA pellets were prepared for extrusion by being dried overnight at 45°C. They were then fed into a small hole at the top of a RH2000 capillary rheometer at 230°C, as seen in Figure 4. At the bottom of the hole, a single-screw feeder brought the PLLA pellets into the system to be heated and pressurized to ensure its melting. The pressure was then increased to approximately 20 MPa. until the molten PLLA passed through the die, which was 1 mm in diameter, at a rate of 2 mm/min. As such, the volumetric flow rate was 1.57 mm3/min. The end of the extruded fiber was then attached to a rotating spool as seen in Figure 5 as the extruder continued to run. The resulting thickness of the fiber was dependent on the speed at which the spool rotated, as roller speed changed while volumetric flow rate remained constant as Table 1 shows. Ten spools in total produced by this process were used for the
characterization of PLLA through various tests. Spool 7 was used for drawing and annealing because of its large quantity of highly consistent fibers, while spool 8 was analyzed using XRD in order to determine the effect of roller speed on polymer structure due to its particular thinness. Table 1. Roller Speeds during Extrusion
Spool Number Roller Speed (m/min)
1 13
2 13
3 13
4 7
5 17
6 25
7 7
8 33
9 8.5
10 33
3.3 Drawing the Fibers
Prior to the drawing process, the diameters of the undrawn PLLA fibers were measured using a micrometer. The fiber was placed between the two arms of the caliper mechanism, one of which was slowly moved towards the other until the fiber became clamped between them. The micrometer was used to measure the displacement of the rod in order to determine the diameter of the fiber. In this experiment, five measurements were recorded at different locations along the same fiber and the average of the measurements was then used to determine the pre-drawing diameter. The fiber was then held approximately 1-2 mm over a 120°C hot plate and manually drawn by holding one end of the fiber at one edge of the hot plate while pulling the other end across to the other edge, as seen in Figure 6.
Then, the diameter of the drawn fiber was remeasured using the same methods using the micrometer. These measurements were used to determine the draw ratios of the PLLA fibers. The same process was then repeated with the hot plate set at a temperature of 110°C. 3.4 Annealing
Extruded PLLA fibers were placed in a glass Petri dish and heated in an oven set at 150°C for 19 hours and then allowed to gradually cool to room temperature before being prepared for XRD analysis. 3.5 Testing Tensile Strength
The tensile strength of the extruded PLLA fibers was tested using a Mechanical Testing System, otherwise known as MTS, shown in Figure 7. A length of fiber about 10 cm long was cut from the spools of fiber. Each end of the fiber was wrapped in tape, leaving about a 5 cm gauge length between the two pieces of tape. The excess parts of the fiber that extended past the tape were then cut off. Three samples each of undrawn fibers and fibers drawn at 120°C and 110°C were stretched in the MTS at a speed of 5 mm/min until they failed, or snapped. Using this data, stress-strain curves depicting the yield point, failure point, and Young’s modulus were graphed. During elastic deformation, the temporary deformation of a polymer occurs in a way describable by a constant Young’s modulus, as stress is then directly proportional to strain.
In elastic deformation, once the polymer is released it will return to its original shape. However, beyond the yielding point, deformation is permanent. This is known as plastic deformation. The points at the beginning and end of the elastic stage were used to determine the Young’s modulus, which is the slope of the linear section of the curve. 3.6 XRD An X-ray diffractometer was used to evaluate the crystallinity of the PLLA and the orientation of its molecules, as well as to
compare the properties of annealed fibers and drawn fibers to those of untreated fibers. 1-in long samples of annealed, drawn, and untreated fibers were mounted to wooden dowels that were then clamped to the XRD stand, as in Figure 8. The diffractometer was set to 40 kV of voltage and 40 mA of current. The General Area Detector Diffraction System (GADDS) was programmed to analyze the samples with the detector angle at 26°, Ω (sample stage oscillation) at 1°, and χ (vertical fixed angle) at 45°. The distance from the detector to the sample was set to 8.88 mm and the size of the 2-D detector display was 512 pixels by 512 pixels. Each test was conducted for 10 minutes with continuing oscillations throughout that period. Using the same parameters, the scattering of a sample of air was also measured and subtracted from the data for each subsequent test so that any scattering not caused by the PLLA itself could be subtracted out of the data in order to provide a clearer profile. 4 Results and Discussion 4.1 DSC Results
The results of the DSC test are represented as a graph of three lines depicting the heating, cooling, and reheating of the heat cycle programmed for the PLLA sample, as seen in Section 8.1. The initial heating is represented by the red line, the cooling is represented by the blue line, and the reheating is represented by the green line. The lines depicting the two-minute isothermal stages that occurred between the heating and cooling stages and the cooling and reheating stages, as well as the final cooling, are not displayed on the graph since they convey no novel information. Initial heating and cooling were done to obtain an amorphous structure in the polymer to analyze its crystal transition. The relative flatness of the first heating curve indicates that the sample tested by the DSC did not have a significant amount of water. If the sample did contain a substantial amount of water, it would have lost water through
evaporation, thus causing an endothermic reaction and a drop in the graph in this region. The glass transition temperature of PLLA was experimentally determined to be approximately 63°C. Scientific literature regarding the glass transition temperature of PLLA identifies it at around 58°C, which is slightly lower than the value found through this experiment.24 The higher glass transition temperature may have been due to the relative lack of additives in the tested PLLA sample. The determined temperature was about 20°C higher than the normal human body temperature, implying that PLLA would not undergo a transition and lose its properties in the body.
The crystallization of the polymer was not observable in the first heating cycle but was observed in the second heating cycle as the peak at approximately 133°C. This process was exothermic because the polymer chains were reorganizing to form as many bonds as possible so as to obtain a structure requiring the least possible energy.25 The melting point of the polymer is represented on the graphs of both heating curves, first at approximately 188°C and then at approximately 170°C during the second heating. The former data point was somewhat higher because in the second round of heating, the sample was already more amorphous and therefore easier to melt. The relatively high glass transition temperature and melting temperature of PLLA suggest that it would not undergo structural changes due to temperature in normal conditions of the human body, thus making it a suitable material for biomedical applications. This data from the DSC scan helped determine the temperature at which to extrude the PLLA fibers. In order for extrusion to be possible, the polymer has to be in a molten state, which occurs after the steep dip in the graph, or the melting point. However, the temperature for extrusion should not be too far beyond the melting point since higher temperatures can cause the polymer to degrade. PLLA degrades slightly at all temperatures, but at about 240°C, the degradation becomes so severe
that the moisture of the sample no longer matters; the polymer will degrade regardless of how dry the sample is.26 Since the melting point was found to be approximately 188°C from the DSC analysis of PLLA shown in Section 8.1, the temperature for extrusion was set to 230°C. This temperature was also selected with consideration to PLLA’s degradation. Similarly, the DSC results were used to determine a suitable temperature range for drawing the PLLA fibers. The temperature must be above the glass transition since that is the point at which the fiber becomes rubbery and flexible, but the temperature must also be below the melting point. Otherwise, the fiber would simply melt. Since the glass transition was found to occur at 63°C and the melting point at 188°C, temperatures of 110°C and 120°C were chosen to draw the fibers. 4.2 Draw Ratios
The draw ratios of two samples of PLLA fibers were calculated by dividing the average initial cross-sectional area by the average cross-sectional area after drawing. Materials that are highly oriented have higher draw ratios, because more of their polymer chains are oriented in the same direction, producing a longer fiber. As a
Table 2: Draw Ratios
material melts, it transitions to an amorphous state, becoming less organized. 120°C is closer to the melting temperature of PLLA than 110°C. Therefore, PLLA is likely to be less oriented, and consequently to have a lower draw ratio, at the higher temperature. At 110°C, the fibers could be drawn to a greater length than were the fibers drawn at 120°C. The collected data, visible below in Table 2, supports these theoretical predictions. 4.3 Mechanical Testing System (MTS) Results: Tensile Strength
The data from the MTS was used to construct average stress-strain curves for undrawn PLLA fibers, seen in Section 8.2.1, fibers drawn at 110°C, seen in Section 8.2.2, and fibers drawn at 120°C seen in Section 8.2.3. This allowed for the mean calculations of the Young’s modulus, the percent strain at the yield point, and the stress at the yield point to be made. The Young’s moduli were determined by calculating the slopes of the most linear portions of the stress-strain curves, while the strains and stresses at the yield point were derived from the average values over a small range in which the graphs curved, demonstrating mechanical yielding. The stress-strain curves of the PLLA samples
Average Diameter (mm)
Average Radius (mm)
Average Cross-sectional Area (mm2)
Average Draw Ratio
(I) Before Drawing
0.298 0.149 0.069
(I) After Drawing at 110°C
0.099 0.050 0.008 8.62
(II) Before Drawing
0.257 0.128 0.052
(II) After Drawing at 120°C
0.113 0.057 0.010 5.20
can be divided into three segments: elastic, viscoelastic, and plastic. These three segments are demarcated by the points labeled B, M, Y, and F on the stress-strain curves, as seen in the graphs in Section 8.2. As the non-recoverable deformation of the plastic stage renders most biomaterials useless for their intended purposes, the elastic and viscoelastic stages are the most relevant to this paper.
Young’s modulus describes a substance’s resistance to elastic deformation; therefore higher values are preferable. Accordingly, the fibers drawn at 110°C were more optimal because they had a measured mean Young’s modulus of 6.6 GPa whereas the fibers drawn at 120°C had a measured mean Young’s modulus of 4.8 GPa. Both sets of drawn fibers were superior to undrawn fibers, which had a mean Young’s modulus of 2.3 GPa.
Polymers can be useful until their viscoelastic stage ends, the strain and stress at the yield point are still significant, unlike the values at the failure point. Fibers drawn at 110°C were able to deform to a maximum
percent strain of 3.3 until they yielded at a stress of 132.9 MPa, whereas fibers drawn at 120°C were slightly worse in this regard, on average deforming to a maximum percent strain of 3.2 and yielding at a stress of 107.6 MPa. Undrawn fibers were significantly inferior in this regard, having a mean percent strain of 2.1 and a mean yield stress of 40.4 MPa as shown by Table 3. Overall, drawn fibers are mechanically superior to undrawn fibers because drawing over heat uniformly orients the individual molecules within a PLLA fiber. Fibers become more difficult to pull apart due to the greater number of bonds formed during orientation, improving tensile strength in general and causing the increase in mean Young’s moduli, stresses at yield, and percent strains at yield observed in the data.
Table 3. Tensile Strength Properties For
Undrawn and Drawn Fibers
Mean Young’s Modulus (GPa)
Mean Strain at Yield (%)
Mean Stress at Yield (MPa)
Undrawn Fibers 2.3 2.1 40.4
Fibers Drawn at 110°C
6.6 3.3 132.9
Fibers Drawn at 120°C
4.8 3.2 107.6
4.4 XRD Results: Crystallinity and Orientation
There were two main processes that were carried out on the extruded PLLA fibers: drawing and annealing. The properties of the PLLA samples were altered after each procedure. Then, X-ray diffraction was carried out on the samples in order to determine the effects of different processes on the fibers’ crystallinity and orientation. The effects of the temperature at which fibers were drawn and the rates of spooling of the fibers were additionally analyzed in terms of the XRD data.
The data from the XRD were used to create graphs depicting Intensity versus Two-Theta and Intensity versus Chi. The Intensity versus Two-Theta graphs showed the scattering in the plane. In other words, the arcs of the graphs were collapsed and the intensities along each arc combined to find the total intensities. This Intensity vs. Two-Theta graph helps determine the crystallinity of the sample since crystalline areas appear as sections of brighter intensities on the image and thus translate to areas of higher peaks on the graph. Sharp, narrow peaks represent crystalline areas and broader slopes represent amorphous areas. The higher the peak, the more crystalline the area is. The crystalline area, i.e., the area under the sharp peaks with the broad slopes subtracted out, divided by the total area under the curve is the percent crystallinity. Table 4. Structural Properties of Sample PLLA Fibers
Since the Intensity versus Two-Theta graph collapses the data along the arcs, deviations within each arc are not shown. These deviations, which appear as streaks, rather than full bands, in the detector images, indicate orientation of the crystals. Thus, another graph, the Intensity versus Chi graph, is needed to depict this data. The Intensity versus Chi graph shows the scattering that occurs outside of the plane. This graph collapses the data so the points along each radial line extending out from the center of the circle are added together. This graph depicts any orientation that occurs in the sample as peaks in the graph. Graphs with peaks show orientation while graphs that plateau show a lack of orientation. 4.4.1 Effects of Drawing on PLLA Fiber
In order to determine the effect of the drawing process on the properties of the PLLA fiber, comparisons were made between drawn and undrawn fibers. Fibers that were not drawn, as in Image 8.3.1.1 showed amorphous scattering in the detector images, indicating a lack of crystallinity. This conclusion is reinforced by the broad features of the Intensity versus Two-Theta graph, as in Image 8.3.1.2. When analyzed with the XRD, the fiber drawn at 110°C, visible in Section 8.3.2, showed crystallinity and orientation. In the detector image visible in Image 8.3.2.1, there were clear bands of higher and lower intensities, which correspond to the sharp peaks that rise out of the
Sample Description Crystalline or Amorphous
Degree of Crystallinity (%)
Oriented or Unoriented
Undrawn, Unstretched (7.3.1) Amorphous 0 Unoriented
Drawn at 110° C, Unstretched (7.3.2)
Crystalline 14 Oriented
Thin (7.3.5) Amorphous N/A Unoriented
Undrawn, Unstretched, Annealed (7.3.6)
Crystalline 45 Unoriented
Drawn at 110° C, Stretched Crystalline 22 Oriented
Drawn at 110° C, Annealed Crystalline 43 Oriented
broad slopes in the Intensity versus Two-Theta graph, Image 8.3.2.2. This demonstrates the crystallinity of the material. Meanwhile, the orientation can be seen in the streaked pattern of the arcs in the detector image and the peaks seen in the Intensity versus Chi graph, Image 8.3.2.3. 4.4.2 Effects of Annealing on PLLA Fiber
Undrawn fibers displayed a high level of crystallinity when annealed, as seen in Section 8.3.5, as evidenced by the bright bands in the XRD detection image and the sharp peaks in the graph of Intensity versus Two-Theta. Undrawn fibers that were not annealed, which can be seen in Section 8.3.1 displayed an amorphous structure, with only a broad scattering peak on the graph of Intensity versus Two-Theta and a broad rather than a narrow band on the XRD detection image. This supports the conclusion that annealing fibers enables the polymer to form a crystalline structure.
Furthermore, the undrawn fibers had little orientation in their crystal structure, which is demonstrated by the plateau in the graph of Intensity versus Chi, in Image 8.3.5.3, and annealing did not change this. In both the annealed and the unannealed undrawn samples, there was a plateau in the graph of Intensity versus Chi, corresponding to a lack of crystal orientation.
Moreover, annealing consistently increased the crystallinity of drawn fibers. This is supported by the fact that there is a broad base in the graph of Intensity versus Two-Theta for drawn but unannealed fibers, as seen in Sections 8.3.2.2, 8.3.3.2, and 8.3.6.2, while there is less broadness, characteristic of lower amorphous scattering, in the drawn and annealed fibers, as seen in Section 8.3.7.2.
Annealing for drawn fibers additionally appeared to increase their orientation. The graph of Intensity versus Chi for drawn and unannealed fibers found in Section 8.3.2.3 contains a broad peak, and the detector image shows several bright spots at the same radius from the center, rather than a band. This corresponds to the orientations of polymers within the fiber. However, for drawn and annealed fibers, graphs for which are in Section
see 8.3.7, the graph of Intensity versus Chi shows a much steeper peak in intensity, while the detector image shows several extremely narrow bright spots that resemble the diffraction pattern of a single crystal. These differences signify that the drawn and annealed fibers were more oriented than the drawn and unannealed fibers, perhaps due to the fact that drawn fibers already had directions of orientation along which further oriented crystals could form during annealing. 4.4.3 Effects of MTS Stretching on PLLA Fiber
Several samples were analyzed via XRD after having been stretched by the Mechanical Testing System to determine their mechanical strength. However, the XRD profiles of these samples are functionally indistinguishable from those of unstretched samples. As such, the experiment supports the null hypothesis there are only negligible effects. 4.4.4 Effects of Roller Speed on PLLA Fiber
Thicker and thinner fibers were analyzed using XRD; thicker fibers corresponded to a lower roller speed during extrusion, while thinner fibers corresponded to a higher roller speed, due to the constant flow of polymer out of the extruder. Analysis of the XRD data for thin undrawn fibers seen in Section 8.3.4 shows no significant variation from the XRD data for thick undrawn fibers seen in Section 8.3.1, with both sets of fibers demonstrating a low level of both crystallinity and orientation. Thus, roller speed has no significant effect on the structure of the PLLA fiber. 5 Conclusion
A versatile polymer, PLLA can be processed into many different biomedical devices because of its properties of biodegradability, biocompatibility, and strength. During this experiment, PLLA was fabricated through melt-extrusion, put through several processes including drawing and annealing, and finally characterized to analyze the effects of the processes on the strength of the fibers.
A current important issue within the biomaterials science field is the processing of biodegradable polymers and the methods by which to improve it through the altering of physical properties. Using MTS, the tensile strength properties of drawn fibers as compared to undrawn fibers were analyzed. Through the drawing process, the Young’s Modulus of PLLA fiber increased by a magnitude of approximately two times the original at a draw temperature of 120°C and four times the original at a draw temperature of 110°C. The percent strain at yield increased by an approximate factor of 1.5, and the stress at yield improved by an approximate factor of three times the original. Not only does the drawing process improve the mechanical properties of PLLA fibers, but there is also an ideal temperature range to optimize such improvements that lies between a determined temperature that is high enough to prompt glass transition, but low enough to prevent melting. Within this range, as the results of this experiment have proved, the process of drawing improves both the crystallinity and the orientation of the molecular structure of PLLA fibers. In addition, the annealing process increases the crystallinity for undrawn and drawn fibers alike. However, the annealing process only marginally increases the orientation of fibers that were already drawn. This is due to the drawing process having already oriented the fiber so that when the fiber undergoes the annealing process, there are already directions of orientation along which further oriented crystals can form. In this experiment, the mechanical strength properties of annealed drawn fibers were not assessed due to time limitations, so further research could be pursued upon this aspect to determine how the process of annealing drawn fibers improves its tensile strength, a necessary aspect in customizing biomedical devices. PLLA can be modified to varying degrees of strength and flexibility through drawing and annealing processes to accommodate different biomedical devices.
Through the simple, cost-effective technique of drawing, fibers can undergo a significant increase in their tensile strengths, rendering them ideal components for sutures, vascular grafts, and nerves. By simply stretching fibers while concurrently heating them, industrial
manufacturers can efficiently augment the mechanical strength of the PLLA fiber, including superior properties in the viscoelastic and plastic regions of deformation, therefore making the polymer more suitable for applications that require large volumes of stronger material. Such applications might include replacement ligaments, tendons, or other high-load body parts. Future research would help in determining how cost-effective drawing would be in large-scale manufacturing operations, although its speed and low energy requirements bode well for its industrial applications. Since PLLA is an extremely versatile and economical polymer, capable of undergoing significant changes for little cost, it will inevitably broadly benefit the biomaterials industry and the medical community. 6 Acknowledgements
This paper would not have been possible if not for the tireless dedication of the mentors and various others who assisted the authors in performing experiments, analyzing data, and writing the paper itself. The authors would like to thank mentors Dr. Thomas Emge, the Chief Crystallography Engineer of Rutgers University, and Dr. Sanjeeva Murthy, Associate Research Professor at the New Jersey Center for Biomaterials at Rutgers University, for constantly sharing support, enthusiasm and knowledge through a combination of lectures and direct assistance with experiments. Their contributions were invaluable at every step of the research process, from first formulating an overall objective to analyzing reams of x-ray diffraction data. Additionally, the authors would like to extend thanks to Sid Borsadia for his help in the extrusion, DSC testing, and mechanical testing components of the paper. Thanks is also due to Juilee Malavade, the RTA assigned to this paper, for her assistance in editing and focusing the paper overall, as well as in simply motivating the authors and ensuring that work be completed. Thanks to all of the other RTAs who assisted with the project in giving advice or facilitating transportation, including Eamon Collins, Edmund Han, Rowen Kanj, and Kelly Ruffenach. Moreover, thanks to Joshua Kim, Nicholas Faenza, and Linda Sung, instructors of “Everything’s Materials” course at the Governor’s School of Engineering and
Technology, for discussing at length the subjects of the paper. Thanks also to Sarah Sprawka of Purac Pharmaceuticals for generously donating the PLLA samples that were used in this paper. Finally, thanks to the Governor’s School of Engineering and Technology in general and all of its sponsors, including Rutgers, the State University of New Jersey, the Rutgers School of Engineering, the State of New Jersey, Silverline Windows, Lockheed Martin, South Jersey Industries, Novo Nordisk Pharmaceuticals, Inc., and NJ Resources. Thank you to both Dean Jean Patrick Antoine and Director Ilene Rosen, for providing this program and excellent research opportunity. 7. References 1. Murthy, Sanjeeva. “Polymers in Biomedical Devices for use in Regenerative Medicine.” Lecture, NJCBM from Rutgers University, Piscataway, NJ, July 2, 2015. 2. Ibid. 3. Ibid. 4.Allan S. Hoffman, Jack E. Lemons, Buddy D. Ratner and Frederick J. Schoen, An Introduction to Materials in Medicine (Academic Press, 1996), p. 15. 5. Murthy, Sanjeeva. “Polymer Properties and Future Directions.” Lecture, NJCBM from Rutgers University, Piscataway, NJ, July 3, 2015. 6. Intro to the Science and Engineering of Materials (University of Virginia, 2004). 7. Murthy, Sanjeeva. “Polymers in Biomedical Devices for use in Regenerative Medicine.” Lecture, NJCBM from Rutgers University, Piscataway, NJ, July 2, 2015. 8. “Polymer Properties.” http://faculty.uscupstate.edu/llever/Polymer%20Resources/Mechanical.htm (retrieved July 5, 2015). 9. Murthy, Sanjeeva. “Polymers in Biomedical Devices for use in Regenerative Medicine.” Lecture, NJCBM from Rutgers University, Piscataway, NJ, July 2, 2015. 10. Lin Xiao, Bo Wang, Guang Yang and Mario Gauthier. “Poly(Lactic Acid)-Based Biomaterials: Synthesis, Modification and
Applications.” Biomedical Science, Engineering and Technology. (2004). 11. Juha-Pekka Nuutinen, Claude Clerc, Raija Reinikainen, and Pertti Tormala. “Mechanical properties and in vitro degradation of bioabsorbable self-expanding braided stents.” Journal of Biomaterials Science, Polymer Edition. (2003). 12. Murthy, Sanjeeva. “Polymers in Biomedical Devices for use in Regenerative Medicine.” Lecture, NJCBM from Rutgers University, Piscataway, NJ, July 2, 2015. 13.Ibid. 14. Murthy, Sanjeeva. “Polymers in Biomedical Devices for use in Regenerative Medicine.” Lecture, NJCBM from Rutgers University, Piscataway, NJ, July 2, 2015. 15. Ibid. 16. Fatahi, Shokoh. “Extrusion Processing.” http://aiquruguay.org/congreso/download/P5.pdf (retrieved July 5, 2015). 17. Kopeliovich, Dmitri. “Annealing of Plastics.” Substech: Substances and Technology, Knowledge Source on Material Engineering. http://www.substech.com/dokuwiki/doku.php?id=annealing_of_plastics (retrieved July 5, 2015). 18. “How to Analyze Polymers Using X-ray Diffraction.” (International Centre for Diffraction Data.) 19. “Anisotropy and Isotropy.” NDT Resource Center. https://www.nde-ed.org/EducationResources/CommunityCollege/Materials/Structure/anisotropy.htm (retrieved July 5, 2015). 20. “How to Analyze Polymers Using X-ray Diffraction.” (International Centre for Diffraction Data) 21. Emge, Thomas. “X-Ray Diffraction (XRD).” Lecture, Rutgers University, Piscataway, NJ, July 3, 2015. 22. Allan S. Hoffman, Jack E. Lemons, Buddy D. Ratner and Frederick J. Schoen, An Introduction to Materials in Medicine (Academic Press, 1996), p. 55. 23. Paul J. Schields. “Bragg’s Law and Diffraction: How waves reveal the atomic structure of crystals.” Center for High Pressure Research.
http://skuld.bmsc.washington.edu/~merritt/bc530/bragg/ (retrieved July 5, 2015). 24. David E. Henton et al. “Method for Producing Polylactic Acid.” Membrane Technology. http://jimluntllc.com/pdfs/polylactic_acid_technology.pdf (retrieved July 20, 2015). 25.Murthy, Sanjeeva. “Polymer Properties and Future Directions.” Lecture, NJCBM from Rutgers University, Piscataway, NJ, July 3, 2015. 26. V. Taubner and R. Shishoo, “Influence of Processing Parameters on the Degradation of Poly(L-Lactide) During Extrusion,” Journal of Applied Polymer Science, 79, 2131 (2000). 27. “Rules and Regulations Under the Textile Fiber Products Identification Act.” https://www.federalregister.gov/articles/2000/11/17/00-29468/rules-and-regulations-under-the-textile-fiber-products-identification-act (retrieved July 18, 2015). 28. “X-Ray Powder Diffractometry.” http://lipidlibrary.aocs.org/physics/xray/index.htm (retrieved July 20, 2015).
8 Graphs 8.1 DSC Graphs PLLA DSC Results
This DSC graph shows the acceptable ranges for drawing and extrusion, which were used to process PLLA for characterization. Drawing must occur at a temperature higher than Tg so the polymer can be bent and moved without shattering, but lower than Tm so the polymer does not melt on the draw frame out of its fiber form. Extrusion must occur at a temperature higher than Tm so the polymer is molten enough to flow but lower than approximately 240°C so the polymer is not degraded. 8.2 MTS Graphs and Data
Each of the following in this series of stress-strain curves (the first of which was obtained by mechanically stretching undrawn fibers, the second by mechanically stretching fibers drawn at 110°C, and the third by mechanically stretching fibers drawn at 120°C) contain three primary sections, demarcated by the points B, M, Y, and F. The first area, B-M, is the elastic region, the second, M-Y, the viscoelastic region, and the third, Y-F, the plastic region, after which failure occurs and the fiber snaps. Although the B, M, Y, and F points are only distinctly labeled on one particular curve, the placements of the points on the other two curves shown in any given figure are comparable.
In the linear, elastic region, stress is directly proportional to strain (the constant of proportionality being the Young’s modulus of the fiber), and stress is fully reversible. In the subsequent viscoelastic region, creep and necking begin to become deforming factors, and stress is only partially reversible. In the final,
plastic region, any stress is entirely irreversible, and the polymer continues to deform until it ultimately snaps, accompanied by a sharp vertical line in the graph.
In some instances during this testing, however, the fiber began to slip out of the testing system as it neared mechanical failure, causing a gradual downward-sloping curve to appear at the end instead of a sharp drop. Additionally, because of particularly severe slippage in the testing of the samples that had been drawn at 120°C, only the very beginnings of the stress-strain curves from those tests are shown. 8.2.1 Undrawn Fibers
8.2.2 Fibers Drawn at 110°C
8.2.3 Fibers Drawn at 120°C
8.3 XRD Graphs and Data 8.3.1 Sample 1: Undrawn and Unstretched 8.3.1.1: Detector Image
As can be seen from the detector image, the unstretched and undrawn fiber is rather amorphous but still has some crystalline properties, shown by the broad and bright band. The equal distribution of intensity at any given radius from the center shows that untreated PLLA fiber is unoriented. 8.3.1.2: Intensity vs. Two-Theta Graph
The broad peak shows that the material is more amorphous than crystalline. 8.3.1.3: Intensity vs. Chi Graph
The broad plateau in intensity is indicative of this sample’s unoriented structure.
8.3.2 Sample 2: Drawn at 110°C and Unstretched 8.3.2.1: Detector Image
The detector image displays several arcs at different angles. The thin bright arcs are relatively clearly defined, showing that drawing PLLA fiber at 110°C makes its structure more crystalline and oriented. 8.3.2.2: Intensity vs. Two-Theta Graph
There are several very narrow peaks on the Intensity vs. Two-Theta graph, indicating crystalline structure. 8.3.2.3: Intensity vs. Chi Graph
Instead of a broad plateau, there is a single peak indicating a more oriented structure.
8.3.3 Sample 3: Drawn at 120°C and Stretched 8.3.3.1: Detector Image
The detector shows several streaks that arc out from the right center of the detector image. Most of the image shows amorphous areas, but the brighter intensity shows an area with higher crystallinity. Since the bright arc is a short streak rather than a full arc, the graph shows that the crystals are oriented. 8.3.3.2: Intensity vs. Two-Theta
The Intensity vs. Two-Theta graph demonstrates through a series of fairly sharp peaks that the sample in question is relatively crystalline. 8.3.3.3: Intensity vs. Chi
There is a well defined peak evident that shows a fair degree of orientation.
8.3.4 Sample 4: Thin Fiber (Spool 8) 8.3.4.1: Detector Image
This sample is amorphous for the most part, but the bright band provides evidence for some degree of crystallinity. The equal intensity distribution demonstrates that this PLLA sample is also unoriented. 8.3.4.2: Intensity vs. Two-Theta Graph
There is a broad peak that confirms a mostly amorphous structure. 8.3.4.3: Intensity vs. Chi Graph
The lack of peaks in the Intensity vs. Chi graph demonstrates an unoriented structure.
8.3.5 Sample 5: Undrawn, Unstretched, and Annealed at 150°C 8.3.5.1: Detector Image
The detector image shows two well-defined arcs and surrounding bands that signify a high degree of crystallinity in this sample. Due to the equal intensity distribution relative to the center, it can be determined that the material was unoriented. 8.3.5.2: Intensity vs. Two-Theta Graph
The sharp peaks in this graph indicate a highly crystalline structure for the sample. 8.3.5.3: Intensity vs. Chi Graph
There are no distinct peaks, only a broad curve, thus confirming the unoriented nature of the fiber.
8.3.6 Sample 6: Drawn at 110°C and Stretched 8.3.6.1: Detector Image
The detector shows several streaks that arc out from the right center of the detector image. Most of the image shows amorphous areas, but the brighter intensities show areas with higher crystallinity. Since the bright arcs are short streaks rather than full arcs, the image shows that the crystals are oriented. 8.3.6.2: Intensity vs. Two-Theta Graph
The Intensity vs. Two-Theta graph demonstrates that the sample in question is significantly crystalline, due to the single sharp peak at the left and the other, smaller peaks at the right. 8.3.6.3: Intensity vs. Chi Graph
The slightly broad but still well defined peak shows that the sample is oriented.
8.3.7 Sample 7: Drawn at 110°C and Annealed 8.3.7.1: Detector Image
Unlike the other detector images, the image for this fiber shows a full circle of scattering rather than just a partial circle. This is due to different settings on the instruments rather than a difference in the sample. The image shows brighter streaks that sweep out in arcs from the center of the circle. These areas of higher intensity show that the polymer is crystalline. However, since the streaks do not form complete rings, the PLLA crystals are oriented. 8.3.7.2: Intensity vs. Two-Theta Graph
The graph shows two main peaks that depict the crystalline areas. There is very little scattering under the peaks, which means there is not much amorphous material in the fibers. 8.3.7.3: Intensity vs. Chi Graph
Evidence of high levels of orientation can be seen in the single, sharp peak on the right side of the graph.
9 Pictures Figure 1: PLA Formation
27 The image above demonstrates the two main processes of PLA formation. PLA can either be synthesized through hydration reactions of lactic acid molecules (direct condensation route) or through ring-opening reactions with lactide molecules formed from the dehydration of lactic acid (lactide intermediate route). Figure 2: Image of the Differential Scanning Calorimeter (DSC)
The image above portrays the differential scanning calorimeter (DSC), in which samples of PLLA were placed to test for fundamental properties, such as melting temperature.
Figure 3: Image of Extrusion Equipment
This is an image of a capillary rheometer, which was used in the extrusion process. Samples of PLLA pellets were placed into the machine, and then released in the form of fibers. Figure 4: How An X-Ray Diffractometer Works
28. The above diagram demonstrates the fundamental mechanism behind x-ray diffraction, in which X-rays are emitted and then filtered so that only a particular wavelength of light impacts the sample. Then, constructive interference of the x-rays that diffract off of the sample are received and used to construct a characteristic diffraction profile for a substance.
Figure 5: Image of Spooling Equipment
The image above shows the machine used in the spooling process. The extruded PLLA strands were rolled into spools of uniform fiber, whose thicknesses varied based on the spooling rate used. Figure 6: Image of Equipment for the Drawing Process
This image depicts drawing equipment. Strands of PLLA were drawn across the hot plate, shown above the yellow caution sign, at temperatures of 110°C and 120°C during the drawing process.
Figure 7: Image of the Mechanical Testing System (MTS)
The Mechanical Testing System is shown in the image above. Fibers of PLLA were set in this device and then stretched so that certain characteristics, such as stress and strain at yield point, could be determined with the aid of a computer program.
Figure 8: Image of the X-Ray Diffractometer
The x-ray diffractometer, shown in the image above, is used to analyze the percent crystallinity and orientation of a sample by measuring how certain spacings in its molecular structure create constructive interference of diffracting x-rays in accordance with Bragg’s law.