Posted by Cambridge Polymer Group on | Comments Off on A Bit of a Stretch
Given that today is Halloween, this blog entry started with the question of what is the most popular candy? For Massachusetts, the home of Cambridge Polymer Group, that candy is Starburst.[1] Starburst bears a loose association with taffy, which is a candy made by stretching a heated mass of sugar. The act of pulling taffy introduces small air bubbles into the molten sugar, which makes the mixture softer and improves the texture.
Do the Taffy Math
You have likely seen a taffy stretcher at a candy shop. I always thought it was for show, but it turns out that it is a necessary process to make the taffy. Pulling taffy by hand is challenging, given the temperature of the material, the viscoelasticity, and the number of required pulls. What I hadn’t also realized was the complex math that these confectioners were practicing in front of us. As discussed by Jean-Luc Thiffeault, from the University of Wisconsin, taffy pulling is modeled by topological dynamics, and is associated with the dilatation of pseudo-Anosov maps.[2]
I know; I was excited to hear about this association as well, but even more so when I heard that they give a nod to the special integer relationships of Golden and Silver ratios. Any budding theoretical rheologist would grow faint. What this means, essentially, is that the taffy is stretched exponentially overtime. Thiffeault’s article touches on the interesting patent fights that occurred in the 1920s over taffy stretcher designs, going all the way up to the Supreme Court.
Mixing Polymer Melts
The relevance to our work at Cambridge Polymer Group is the mixing of viscoelastic materials, such as polymer solutions and melts, and pharmaceutical compounds. Standard mixing processes used for Newtonian solutions (think sugar mixing into water) do not apply to viscous materials, which requires a great deal more energy and benefit from a combination of shear and extensional flows. Optimization of mixing procedures is key, since polymers and pharmaceutical compounds can be sensitive to heat and mechanical deformation; finding the optimal mixing conditions can preserve the original properties.
So ponder those pseudo-Anosov maps next time you have a salt-water taffy, and consider how this popular candy, at least in Massachusetts, has benefited the plastics and pharma industry. Note: salt water is not a taffy ingredient. The name is allegedly a joke made by a Atlantic City candy shop owner whose taffy was soaked during a storm.
Posted by Cambridge Polymer Group on | Comments Off on Move a Mussel
Biofouling, the adhesion of sea life to ships’ hulls, is a serious problem for all marine vessels. The sticky stowaways significantly increase the hull’s friction; the resulting drag decreases boat speed and increases fuel consumption by up to 40%. In the past, the most effective solution was to dry-dock the boat and manually remove the sea life, which is expensive and labor intensive. In addition to the financial toll of increased fuel usage and dry dock cleaning, marine fouling also contributes to the spread of invasive species.
Anti-Fouling Biocides vs. Non-Toxic Hydrogel
Many commercial anti-fouling agents are composed of toxic chemicals. The obvious drawbacks to a toxic approach are water pollution and the poisoning of non-fouling species. Additionally, anti-fouling biocides need to be replaced frequently, and do not always work well.
The US Naval Coastal Systems Station contracted Cambridge Polymer Group to develop a slow-dissolving hydrogel formulation to clean ships’ hulls underwater. Applied by divers using gun applicators, the hydrogel eliminates the need for dry dock manual removal. Simple dilution of the hydrogel makes it safe for marine life, providing a non-toxic, affordable solution for boat cleaning.
Mussel Attachment Issues
But what if the fouling itself could be prevented? Recently, Harvard researchers unveiled a lubricant-infused coating which stops mussels from attaching to underwater surfaces. Mussels are some of the worst biofouling offenders; they have evolved to stick under the severest of marine conditions. As part of that adaptation, mussels secrete adhesive filaments called byssal threads. These threads are tipped with adhesive plaques which remove water molecules from the wet surface, allowing the plaques to bind to it.
The researchers’ lubricant-infused polymer coating fools the mussel into sensing the hull’s surface as too soft for attachment. This trick discourages the mussel from secreting its adhesive filaments, preventing attachment of the mussel’s foot. Even if a mussel attempts to deploy its byssal threads, this Slippery Liquid Infused Porous Surface (SLIPS) stops the threads from binding. Co-first author Shahrouz Amini speculates the liquid overlayer of the lubricant-infused surfaces resists displacement by mussels’ adhesive proteins.
The amazing adhesive ability of mussels does have positive applications. UC Santa Barbara researchers have developed stronger, more durable dental fillings using catechols, the same chemical groups used by the mussel to promote adhesion on wet surfaces (wet surfaces except for SLIPS, that is). Purdue researchers have inserted catechol into a biomimetic polymer, creating an underwater adhesive that outperforms many commercial adhesives.
Posted by Cambridge Polymer Group on | Comments Off on Leachable Studies of Medical Devices in Complex Biological Environments
Thursday, October 12, 2:10 p.m. EST
Adam Kozak, a senior research scientist at Cambridge Polymer Group, presents “Leachable Studies of Medical Devices in Complex Biological Environments” at Eurofins Lancaster Laboratories’ Extractables and Leachables Symposium for Drugs and Devices in Pennsylvania.
Detailed Extractables/Leachables Studies
Extractables and leachables studies usually follow a two-step program. In the first step, an exaggerated extraction is conducted using simple solvent conditions more aggressive than those anticipated to be realized in a clinical setting in order to determine to determine the complete extraction profile and to identify the potential extraction compounds, desired or undesired. In the second step, a leaching study is conducted that attempts to simulate the clinical environment of the target application. The simulated leaching environment often comprises a more complex biological matrix than those used for extraction, which in turn complicates the chemical analysis assays used to identify and quantify the leaching materials. In this presentation, we show examples of studies that required a more detailed testing assay to identify and quantify compounds coming from implanted medical devices.
Biography
Adam Kozak specializes in the chemical and mechanical analysis of polymer materials and medical devices. He has substantial experience in the use of gas chromatography-mass spectroscopy (GC-MS) for leachables and extractables analysis, trace impurity/contaminant analysis, residual monomer content, unknown compound identification, migration levels, deformulation, and odor analysis by headspace GC-MS and other chromatographic techniques.
Posted by Cambridge Polymer Group on | Comments Off on Fatty Acid and Triglyceride Analysis: Linseed Oil
Figure 1: On left, flax seeds, the source of linseed oil. On right, a representative triglyceride found in a linseed oil.
Linseed oil is derived from flax seeds (Fig 1; typically via pressing and solvent extraction methods). In the presence of oxygen, it polymerizes to form a rigid and hydrophobic solid through a highly exothermic oxidation reaction. This is often misleadingly referred to as “drying”; the process does not depend on evaporation of water but rather on the presence of oxygen to form crosslinks between adjacent triglycerides at points of fatty acid unsaturation (Fig 2). The resulting material is an excellent example of a naturally derived, crosslinked polymer whose properties arise from a complex mixture of its constituents and the processing conditions under which it is formed.
Figure 2: Polymerized and hydrogenated linseed oil. Crosslinks between triglycerides (formerly double bonds) are indicated with arrows.
Due to its easy workability and advantageous “dry” properties, linseed oil is widely used in applications ranging from nutritional supplements (it is rich in Omega-3 fatty acids), as a binder in paint, and in linoleum. In fact, the name “Linoleum” derives from the Latin words for flax (“linum”) and oil (“oleum”). In its native state, linseed oil is a liquid composed of triglycerides (Fig 1) consisting of various combinations of fatty acids—the most common being linoleic acid, alpha-linoleic acid, palmitic acid, stearic acid, and oleic acid.
Figure 3: Example separation of 37 fatty acids by gas chromatography for subsequent quantitation.
The fatty acid fingerprint of a triglyceride-based oil (Fig 3) is a valuable analytical tool for material/compositional identification, correlation to functional properties, good/bad analysis, and quantitative analysis. CPG has a variety of methods which may be leveraged for the analysis of oils—this includes techniques such as gas chromatography (which may be coupled to mass spectrometry; GCMS) which can be used to determine the fatty acid distribution for a sample.
Note that due to the highly exothermic nature of the polymerization process, linseed oil should be handled with care and is often treated as a fire hazard. Over the years many fires have been attributed to the spontaneous combustion of oil soaked rags, often abandoned after a painting job. Such rags are especially dangerous because they present a very high surface area and accelerate the oxidation reaction. If left balled up, temperatures may rise sufficiently high to ignite the entire mass. The Massachusetts Office of Public Safety and Security offers clear guidelines for the safe disposal of such materials.
Working with natural oils? Looking to better understand differences between performance of naturally derived materials? Contact us to see how our team may be able to assist in your project.
Posted by Cambridge Polymer Group on | Comments Off on CPG Awarded Patent for Degradable Hydrogel
Cambridge Polymer Group has received notification of the award of their patent “Thiolated PEG-PVA Hydrogels” (14/328,176). This patent describes a new way of creating hydrogels from a conventional biomaterial poly(vinyl alcohol). The resulting hydrogels cure under physiological conditions with no toxic crosslinkers or bi-products and can be tuned to degrade over periods of weeks.
They are therefore likely to see value in drug release, temporary tissue bulking or scaffold applications, and although they can be cured in vitro, they appear particularly well suited to in vivo applications. In fact, we are already working to commercialize this material through the recent award of an NIH Phase 1 SBIR grant in the field of retinal detachment.
Posted by Cambridge Polymer Group on | Comments Off on Needle in the Haystack: What’s Buried in Your Polymer LC-MS Data?
CPG Webinar – Thursday, October 5, 2 p.m. EST
LC-MS is a widely used analytical technique for characterization of polymer additives, extractables and leachables, degradation products, APIs, drug release studies, and material stability. Typical LC-MS studies however usually focus on small molecules rather than the polymer or excipient components themselves. Structured appropriately, methods for the LC-MS analysis of polymers can yield large, complex datasets that can reveal valuable structural information about polymers and oligomers present in a medical device or pharmaceutical product. Such techniques can help identify the root cause for lot to lot variability or underlying reasons for why polymer blend A is “good” while polymer blend B is “bad.”
Join us for a CPG webinar that will walk through the basic principles and limitations of conducting LC-MS on polymers and oligomers for the purpose of performing structural characterizations, repeat unit analysis, charge state analysis, and molecular weight determination. Key variables such as material ionizability, separation mode, and mobile phase considerations will be discussed, as well as mass spectral data analysis techniques such as two dimensional contour plot visualizations, which can reveal a wealth of data “buried” under the total ion chromatogram. The presentation shall cover specific applications for complex polymer systems such as ethoxylates and hydrogel precursors/degradation products.
Your webinar presenter, Adam Kozak, is a research scientist and biomedical engineer at Cambridge Polymer Group, where he specializes in the chemical analysis of polymer materials. He has substantial experience in chromatography techniques including trace impurity/contaminant analysis, residual monomer/solvent content, extractables/leachables, cleanliness analysis, unknown compound identification, deformulation, migration analysis, molecular weight analysis, and odor analysis. He has managed the development and validation of many custom analytical methods, including extraction and recovery of target analytes from complex polymer and biological matrices.
Posted by Cambridge Polymer Group on | Comments Off on Correlating Melt Flow Index to Molecular Weight
The certificate of analysis for polymer resins often includes a melt flow index (MFI) or melt flow rate (MFR), reported as grams of material/10 min under a specified temperature and load. This testing is normally performed per ASTM D1238 or ISO 1133 using a plastometer. A plastometer consists of a temperature-controlled cylindrical annulus through which a polymer melt is extruded by pressurization with a weight-loaded piston. The amount of material extruded through the die at the bottom of the annulus is measured by weight for a measured period of time. This mass, normalized by time, provides the MFI. It is easy to see that lower viscosity materials will result in a higher MFI, since more material can be extruded for a given amount of time.
How does MFI correlate to the molecular weight of a polymer? At CPG, we often measure molecular weight by gel permeation chromatography or dilute solution viscometry. Both these techniques involve dissolving the polymer in a good solvent to form a dilute solution, so that individual polymer chains can be interrogated directly (in the case of GPC) or indirectly (in the case of viscosity modification in dilute solution viscometry). In MFI testing, the polymer is not dissolved in a solvent, but rather is tested in the melt state. As a result, the MFI has a direct correlation to the polymer’s melt viscosity. For polymer melts, the zero-shear viscosity h0 (or the viscosity at very low shear rates) has a relationship to the weight averaged-molecular weight as follows:
Given the inverse relationship between MFI and viscosity, it is logical to see that the MFI has a relationship to molecular weight as follows, which has been shown empirically for linear polymers:[1]
Bremner and Rudin found values of LLDPE had G values ranging from 2×10-20 to 1×10-24 (10 min/g(x+1)(molx)), and x ranged from 3.9-4.6. In a later article, Bremner found x values between 3.4 and 3.7.[2] The authors cautioned that this relationship becomes tenuous with polymers having variability in branching and polydispersity index. In order for the equation above to be valid, the authors’ note, the viscosity at the MFI conditions normalized by the zero shear viscosity should be a constant for the polymers in a given family. If not, gel permeation chromatography is warranted.
[1] Bremner, T.; A. Rudin, Melt Flow Index Values and Molecular Weight Distributions of Commercial Thermoplastics. J. Appl. Polym. Sci. 1990, 41, 1617-1627
[2] Bremner, T., Cook, D.G., Rudin, A. “Further Comments on the Relations between Melt Flow Index Values and Molecular Weight Distributions of Commercial Plastics,” J. Appl. Polym. Sci. 2003, 43, 1773.
Posted by Cambridge Polymer Group on | Comments Off on The Plastics of Capri
Vitrum Flexile, or flexible glass. Although lost in legend, three different authors provided an account of a glass that could be dented and then repaired in Rome’s first century. According to the Corning Museum of Glass, Petronius (who died in 63 A.D.) told of a drinking vessel presented to Emperor Tiberius (reign 14-37 A.D.). The vessel was thrown to the ground, and though dented, the glassmaker was able to remove the dent with a hammer.
Pliny told a similar story in his encyclopedia, completed around 78 A.D., although his story goes on to say that the glassmaker’s workshop was destroyed so that the value of copper, silver and gold would not be affected by the vitrum flexile.
Dio Cassius provides the third story, in which an architect, who fell out of favor with Tiberius, provided the aforementioned demonstration of denting a glass vessel, then repairing it with his hands.
Unfortunately, no other accounts of vitrum flexile exist beyond these stories. As polymer scientists, we naturally assume that the vitrum flexile was not glass, but rather an early form of plastic, given its mechanical behavior and appearance. Perhaps it was formed of a natural resin, or from a crude polymerization. Ethylene gas was known to be in the Mediterranean around this time (the suspected source of the Oracle of Delphi’s visions). Did a resourceful Greek manage to perform some early free radical polymerization?
Posted by Cambridge Polymer Group on | Comments Off on It’s a Plastic Sort of World
Provocatively Titled Study Explores “All Plastics Ever Made”
A recent study by Geyer et al published in Science Advances takes a wide-ranging look at the production and fate of all plastic produced to date, based on data collated from a range of market research and consulting groups.
Some key observations from the authors’ study are as follows:
The total amount of polymer resin produced from 1950-2015 is approximately 7800 Mt. Production growth has been accelerating with a compound annual growth rate of 8.4%—for perspective, half of the 7800 Mt has been produced in last 13 years!
Assuming an average pellet mass of 25 mg, the total amount of resin produced through 2015 is the equivalent of 3.12 * 1017 pellets.
Plasticizers, fillers, and flame retardants account for approximately 75% of all produced additives between 2000-2014. Antioxidants and heat stabilizers account for approximately 11% of additives produced.
Industrial Use of Plastics
The largest industrial use sector for plastics is packaging. In fact, 42% of all produced nonfiber plastics are used for packaging purposes. The second largest use sector is construction, which makes use of 69% of all PVC produced.
fig. S1. Global primary plastics production (in million metric tons) according to industrial use sector from 1950 to 2015. [1]
The most commonly produced plastics are polyethylene and polypropylene, which make up 57.3% of all polymer resins produced from 2002-2014.
fig. S2. Global primary plastics production (in million metric tons) according to polymer type from 1950 to 2015. [2]
Where Is All That Plastic Now?
It is estimated that 30% of all plastics ever made are currently in use—the rest having been disposed in one way or another. It is estimated that 12% of all plastics disposed of have been incinerated, and only 9% have been recycled. The remainder are in landfills or the natural environment. Note that none of the commonly used plastics are naturally biodegradable; the vast majority are derived from petroleum hydrocarbons.
In addition, there is an increased attention of to the ultimate fate of polymer fibers (such as those used in textile/clothing applications). Environmental accumulation of polymer fibers is in many respects analogous to recent concerns about the deliberate addition of polymer microparticles to consumer products—recall the Microbead-Free Waters Act of 2015 which banned the manufacture and sale of rinse-off cosmetics containing polymer microbeads.
How CPG Can Work With You
At Cambridge Polymer Group, our expertise and analytical capabilities intersect with the topics raised by such studies in multiple ways. We can assist your team in:
Posted by Cambridge Polymer Group on | Comments Off on Additive Manufacturing of Medical Devices
Most traditional machined components involve starting with a standard block of material, and then machining away material to form the final finished device. The advent of 3D printing systems has allowed the opposite approach to machining, where material is sequencing added to a part, in effect growing it from raw material with little scrap material generated, hence the term ‘additive manufacturing’. 3D printing allows generation of more complex geometries, such as porous structures, fully-enclosed hollow features, and finer structure than may be achievable with more conventional milling, lathing, or molding processes. Additionally, 3D printing provides the opportunity for patient-specific implants derived from X-rays or MRIs of the patient’s anatomy.
A variety of materials have been used for 3D printed medical devices, including titanium powder and its alloys, calcium phosphate powder, thermoplastics such as polyether ketone ketone, and UV or light-curable resins. Since 2013, the FDA has been clearing medical devices and drugs made from 3D printing technologies through either the 510(k) process or the emergency need process. In the 510(k) process for a device, a device is cleared by the FDA if it is shown to be as safe and effective as a legally marketed predicate device to which it is substantially equivalent (same intended uses, comparable design and materials). The same tests conducted on machined or molded devices required for clearance, such as biocompatibility, leachables/extractables, mechanical behavior, cleanliness, and functional performance, all apply to 3D printed devices, and currently no additional regulation specific to 3D manufacturing has been established. As of 2016, more than 85 devices manufactured using 3D manufacturing processes have been cleared by the FDA.
3D Printed Medical Devices
Some examples of 3D printed devices that were cleared are shown below, spanning a variety of medical application areas.
2013
Oxford Performance Materials received 510(k) clearance for a 3D printed cranial-facial device made from laser sintering polyether ketone ketone (PEKK), granted in 2013.
2015
DENTCA, a 3D printed denture system, received 510(k) clearance in July of 2015. DENTACA is made from a light-cured resin, and underwent biocompatibility testing per ISO 10993, in addition to human mouth tissue sensitivity contact.
The first 3D printed drug to be cleared by the FDA was Aprecia Pharmaceuticals Co.’s epilepsy drug, Spritam® (levetiracetam) tablets in 2015. Spritam is for treating seizures in patients with epilepsy, and is printed using a method called ZipDose technology, which produces a porous pill that dissolves rapidly with liquid.
MedShape received 510(k) clearance on a Ti6Al4V 3D printed bunion correction system in 2015.
2016
K2M received clearance for titanium printed porous spinal fusion devices made with laser fusion, designed to have surface roughness with feature sizes of 3-5 microns to encourage bone on-growth.
Stryker received 510(k) clearance for a titanium printed lumbar cage to treat degenerative disk disease.
ZB’s reconstructive wedges made from OsseoTi (titanium powder) for ankle fusion received clearance.
Additive Orthopedics cleared for titanium 3D printed devices for foot applications.
Bioarchitects received clearance for 3D printed titanium craniofacial implants.
2017
OssDsign received 510(k) clearance for cranial plates 3D printed with a proprietary calcium phosphate composite reinforced with titanium in 2017.
The Future of Additive Manufacturing
3D printing of drugs could allow hospitals to customize the API dose in each tablet for individual patients, ushering in a new era of personalized medicine. Additive manufacturing may also make medication easier to swallow, both for adults due to improvements in swallow-ability and dissolution, and for children, in that the drug can be made in kid-friendly shapes. At this point, conventional large scale manufacturing continues to be more financially efficient for large quantities of medication, and FDA clearance of 3D manufactured drugs is not easy to obtain.
Additive manufacturing is becoming a more viable alternative manufacturing process for medical devices, since it offers solutions to designs that are unprocessable by conventional manufacturing approaches, readily allows custom device manufacturing, and may present options for on-demand manufacturing of implants. In addition to the standard tests for new medical devices, the areas that currently need addressing for additive manufacturing include process validation procedures and qualification of raw materials (new and potentially used).
