Understanding Your Product’s Performance – The Importance of In Vitro Degradation Studies for Bioabsorbable Implants

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Bioabsorbable polymers were first introduced in the 1960s and have gained traction in the use of medical devices due to their ability to be safely resorbed; thus, leading to a reduction in complications typically observed with the long-term use of foreign material in the human body. These materials are unique in that they can be tailored to a specific application or intended use through various processing techniques to alter their material and physical properties, as well as their degradation profiles. These processing techniques range from different manufacturing processes and sterilization methods to the inclusion of additives during the synthesis of the polymer or during the manufacturing process. Throughout literature, it is noted that these processing techniques can drastically alter the bioresorbable polymers’ properties and degradation profiles; thus, it is imperative that the material and physical properties of the material be captured in a physiologically relevant environment through custom in vitro degradation studies.

At Poly-Med, Inc., we offer a variety of services to characterize the properties and degradation profiles of bioabsorbable medical-grade polymers, components, and devices. These services range from creating custom biomedical solutions to performing analytical evaluations. Poly-Med’s expertise in bioabsorbable polymer analytical evaluations has allowed us to become leaders in performing custom in vitro degradation studies in simulated and controlled environments. Utilizing ASTM standards, primarily ASTM F1635 (Standard Test Method for In Vitro Degradation Testing of Hydrolytically Degradable Polymer Resins and Fabricated Forms for Surgical Implants), the degradation rates and changes in material and physical properties can be characterized to provide an understanding of how the polymer will behave in a physiologically relevant environment. Most importantly, we are able to characterize the molecular weight, strength retention, and mass loss profiles over a designated period of time to construct the degradation profiles.

PMI’s medical-grade bioabsorbable polyester-based polymers typically demonstrate strength loss prior to exhibiting complete mass loss, as depicted in Figure 1. Initially, when these types of implants are placed in an in vitro environment, the implant will interact with the surrounding water molecules leading to water absorption and penetration in the implant itself. While this process is complex, these water molecules will penetrate the implant, which will lead to the polymer chains undergoing hydrolytic degradation cleaving into smaller and smaller chains. Material properties, as well as material processing (e.g., annealing procedures, implant dimensions, etc.), can influence degradation behavior, including monomer content, molecular weight, hydrophilicity, crystallinity, phase microstructure, and thermal properties.

Figure 1: Representative degradation profile observed of bioabsorbable polyester-based polymers

As PMI’s polyester-based polymers undergo bulk erosion, degradation initially occurs within the amorphous microdomains of the polymer (Figure 2). As the degradation process ensues, the implant will lose its molecular weight, which leads to a loss in the material’s strength. This will ultimately lead to the complete mass loss of the polymer over time, as the implant remains exposed to the in vitro environment.

Figure 2: Representative bulk erosion profile observed of bioabsorbable polyester-based polymers

As each implant displays different strength retention and mass loss profiles, in vitro degradation studies provide the ability to accurately characterize the polymer material’s response in a physiological in situ environment; as well as provide an understanding of the effects of various manufacturing processes on the materials’ strength retention and mass loss profiles.

As degradation profiles for these polymers can range from days to years, it can be necessary to characterize the material’s degradation profile along with material and physical properties at an accelerated rate. This can be accomplished by performing in vitro degradation studies at an increased temperature of 50°C compared to the standard temperature of 37°C. By elevating the study’s temperature, the strength retention and mass loss profiles are able to be evaluated and characterized in a shorter duration than compared to the real-time monitoring performed at 37°C.  When degrading at elevated temperatures, a specific polymer’s thermal properties (i.e., glass transition temperature and melting temperature) should be assessed as these properties can significantly alter degradation behavior. Despite providing a quicker timeframe in capturing the degradation profile, in vitro degradation studies should always be conducted at 37°C to ensure an accurate representation of the real-time response under physiological conditions. As degradable polymers are evaluated for new implantable devices, continuous improvement in the standardization for characterizing degradation behavior is essential. Though ASTM F1635 continues to be the go-to guide for researchers, considerations for accelerated in vitro testing and theoretical modeling may assist in establishing a more robust methodology when evaluating bioabsorbable implants for human use.

Contact us today to set up your custom in vitro degradation study!

Poly-Med Chairs WORKSHOP ON THE USE OF ABSORBABLE POLYMERS FOR MEDICAL DEVICES

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In late January, Poly-Med, Inc.’s Chief Technology Officer, Dr. Scott Taylor, organized and chaired a two-day virtual workshop on the use of absorbable polymers for medical devices sponsored by ASTM Committee F04 on Medical and Surgical Materials and Devices.  The ASTM International defines and sets global standards across industries; these standards are used to improve product quality, enhance health and safety, strengthen market access and trade, and build consumer confidence. Standardization is an important factor in the medical field, and being able to lead this committee gives us the platform to influence and help set the optimal standards. Poly-Med contributes using its experience with the development of medical-grade polymers, scaffolds, and devices for use in medical devices and components.

The workshop had three main areas of discussion: 1) Polymer – Device Characterization 2) Novel Polymers and Processes, and 3) Clinical / Regulatory considerations for absorbable polymers for medical devices. As absorbable polymers are designed to degrade in the body, Polymer – Device Characterization is of paramount importance in understanding the mechanism of degradation and the resulting impact on the device, as well as the impact on the surrounding environment. Industry leaders from Johnson and Johnson led this session with the discussion and presentation of in vitro models to elucidate the role of simulated use and its effect on device performance and functionality during the degradation period. When designing such models, researchers have progressed from conducting simplistic experiments (phosphate-buffered saline, body temperature (37°C), gentle agitation), to physiological relevant models that replicate not only internal conditions but use cases and physiological loading specific to the implantation environment. Speakers in this session also provided insight into human factors and how external factors from the user, could alter the outcome of device characterization. Human factor training in device deployment and tissue placement can vary based on surgical training. As we have learned firsthand at Poly-Med, simulated use models and studies lay the foundation for understanding how a material will behave in the body and provides insight into key stages of device performance and eventual resorption.

The second session, “Novel Polymers and Processes,” focused on the two emerging processing technologies of electrospinning and additive manufacturing. Electrospinning is an established methodology that can create fibrous scaffolds that closely align with native tissue topography and mechanics, as wells as size-scale. Electrospinning is a highly tunable, versatile, and commercially successful technology that is based on consistency and scalability. The use of electrospun materials has been catapulted by the ever-expanding cell therapy markets ($11 billion in global financing in 2020). Moreover, the use of these electrospun implants acts not only as delivery and retention vehicles but also as an immuno-protective membrane. By mimicking size-scale and having a high level of porosity, cellular populations can grow on these materials and allow the release of cellular-based materials and chemicals to stimulate a biological response. Additional research is continuing to understand the specific attributes of fiber quality, size, and consistency, as well as their effects on positive clinical outcomes.

Additive manufacturing, with a focus on digital light processing, is another emerging platform that aims to provide patient-specific implants with geometries and properties for peak performance by overcoming the limitations of current manufacturing processes. With digital light processing, though significant enhancements have been made regarding machine and software solutions, material solutions are quite limited. To date, material solutions are limited based on the desired mechanical properties, as digital light processing is more suited for the printing of precise parts rather than load bearing parts. Furthermore, current photoinitiators are cytotoxic due to the high quantities required for curing of the printed parts, and initial evaluations of biocompatible photoinitiators have suffered from uncontrollable swelling when placed in an in situ environment. Desirable traits of such polymer systems include not only long-term manufacturability, but also the thorough characterization of these systems through in vitro models and the complete understanding of the breakdown of products and eventual clearance from the body. At Poly-Med, we continue to perform research into this area and are dedicated to expanding the development of absorbable polymer systems that can benefit device development and human health.         

The final session of the conference presented cases of clinical translation of absorbable devices as well as the regulatory considerations for future absorbable device development. Case examples of absorbable devices spanned uses from wound care and neurological tissue repair to stenting technologies. In each of the presented clinical cases, the importance of implant design and material selection was heralded as being of top importance for successful patient outcomes. With absorbables designed to degrade, a thorough understanding of the implant performance at the clinical level was instrumental in the surgical training and education required for the adoption of absorbables. The final speaker of this session, from the FDA, presented the regulatory challenges facing absorbables. Challenges with these materials stem from their dynamic nature, unique handling control, and processing parameters required of these materials. One specific area of discussion was the evaluation of polymer molecular weight and the use of inherent viscosity in place of molecular weight characterization by gel permeation chromatography (GPC). GPC analysis includes the characterization of molecular weight (both average and number) along with polydispersity. Such information may prove vital in understanding the degradation mechanisms of absorbable materials, though the final result may be the same – a resorbed medical implant.

In summary of the workshop, Dr. Scott Taylor concluded the following: “across the globe the use of absorbable polymers in medical devices continues to grow at an exponential pace. The industry is seeing a resurgence in not only the need for devices to degrade over time to limit patient complications, but also the emerging fields of regenerative medicine and tissue engineering. This committee will continue to define the standards for such devices to ensure consistent quality and establishment of unifying standards for future absorbable material use in the medical fields.” For more information contact us here.

Dr. Shalaby honored with InnoVision Award – The Dr. Charles Townes Individual Achievement Award 2020

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In November 2020, Poly-Med’s founder, Dr. Shalaby W. Shalaby, was awarded the Dr. Charles Townes Individual Lifetime Achievement Award. This awardhonors an individual who has exhibited a sustained commitment to the advancement of technology and the community through his/her technology-oriented and innovative contributions. Such contributions may be business, civic, and/or educational in nature and must benefit the state of South Carolina (SC).

InnoVision describes its awards program as the only one of its kind, calling it “a grassroots, volunteer led non-profit made-up of businesses, organizations, universities, and individuals dedicated to finding innovation and technology in products, services, and education from across the state, and recognizing and honoring peers for achievements in their respective fields.”

At Poly-Med, our roots and humble beginnings have always been a significant part of who we are and who we aspire to be. With the nomination and selection of Dr. Shalaby as the recipient of this award, this award honors Dr. Shalaby as an individual who has exhibited a sustained commitment to the advancement of technology and the community through his/her technology-oriented and innovative contributions. 

In 1990, Dr. Shalaby came to the Upstate of SC to become a bioengineering professor at Clemson University; a post he was offered based on his pioneering work in the field of antibiotic delivery systems, bioadhesives, and bioabsorbable polymers. He was a prolific writer of successful federal grants, which provided research experience and financial support to scores of Clemson University graduate students. In 1993, he founded Poly-Med, Inc. in the Clemson Research Park, where he built two state-of-the-art R&D and manufacturing facilities, which served as a training ground for life science students at Clemson University. 

In the twenty years Dr. Shalaby called the Upstate home, he brought honor and distinction to the Clemson University institution and numerous graduate students, who had the privilege to have him as a mentor. Additionally, South Carolina served as a place where he demonstrated that innovation could flourish. Decades before there was talk of creating a “knowledge economy” in the state, Dr. Shalaby was a living spirit of innovation, entrepreneurship, and job creation in his work at Clemson University and Poly-Med. While he had numerous opportunities to have his company acquired by giants in the life science industry, he chose to remain in the Upstate. He cherished the relationships and close ties with Clemson University and the opportunities of providing young, innovative minds hands-on experience in a real-world lab setting and the ability to create real-world life science breakthroughs.

Dr. Shalaby’s legacy of innovation will continue far into the future due to his impact on the lives he touched. His family and the Poly-Med team continue to mature and commercialize his ideas into the next generation of medical device innovations.  

More about the Innovision Awards

InnoVision Awards, established in 1999, is South Carolina’s premier organization dedicated to the advancement of innovation and technology. InnoVision is the only program of its kind – a volunteer-led non-profit organization comprised of public and private partners from businesses, organizations, universities, along with individuals dedicated to discovering innovation and technology in products, services, and education from across the state of South Carolina.  InnoVision seeks to recognize and honor peers for their achievements in their respective fields and the award is a  mark of distinction for outstanding leadership, innovation, and technological excellence. 

Customized Delivery with Resorbable Polymers

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Polymeric drug delivery systems have undergone significant development in the last two decades.

Polymeric drug delivery has defined as a formulation or a device that enables the introduction of a therapeutic substance into the body.  Biodegradable and resorbable polymers make this possible choice for lot of new drug delivery systems.

Challenges of drug administration:

Administration of a therapeutic requires optimization of dosing regimens to maximize therapeutic benefits while minimizing unwanted side effects to patients. This optimization is governed by four (4) basic pharmacokinetic principles: 1) absorption, 2) distribution, 3) metabolism, and 4) excretion. For any given active pharmaceutical ingredient (API), a number of considerations must be taken into account when designing dosage regimens which include: 1) routes of administrations, 2) site of therapeutic action, 3) the necessity of maintenance doses to ensure long-term therapeutic benefit, and 4) size of the therapeutic window.

Controlled release drug delivery systems:  

Controlled release drug delivery systems have the potential to augment both the bioavailability and distribution profile of a given API. These systems have the ability to deliver APIs at a constant rate over long periods of time, resulting in decreased fluctuations in drug concentrations outside of a given APIs’ therapeutic window. In turn, this can decrease the dosing frequency for a given API and ultimately lead to increased patient compliance. The controlled release of APIs formulated for oral dosing is well-established through the use of complexation resins and coated reservoir systems. In contrast, non-oral controlled release drug delivery systems have historically been more challenging.

Parental drug delivery (e.g., intramuscular, intravenous, and subcutaneous administrations) is required for a number of APIs due to factors that include low bioavailability and a low tolerance for the chemical environments of the stomach and/or GI tract. Recent advances in excipient drug delivery techniques for parental administration have improved the ability to control a given API’s systemic delivery rate.

Electrospun materials:

Bioresorbable electrospun materials are an ideal excipient system given their ability to release APIs in a controlled manner over days rather than minutes/hours. These materials are also optimal due to their ability to act as a scaffold for large quantities and a variety of APIs while maintaining their biological activity. Bioresorbable electrospun materials can be degraded via natural metabolic processes and do not require surgical removal post-implantation.

Electrospinning is a process of manufacturing non-woven fibrous materials where a high voltage is applied to a probe connected to a polymer solution (which may contain an API). Once a sufficient amount of charge has accumulated to break the surface tension of the solution, a cone will form that allows for a liquid stream of polymer to be ejected at a continuous rate towards a spool. This material is then collected on the spool and can be used for downstream processing. Fibers produced via electrospinning exhibit diameters on the submicron scale (µm), causing these materials to have high surface area to volume ratios. Electrospun materials have successfully been produced for biomedical purposes ranging from controlled-release orally-dosed APIs, to wound healing applications.

Case study of successful preclinical long-term drug delivery strategy: Cisplatin

Various strategies have been developed for increasing the therapeutic benefits of certain APIs while decreasing their toxicity. Cisplatin is a highly toxic chemotherapeutic agent commonly used to treat a variety of different cancers. Cisplatin induces cell-death by causing non-specific DNA crosslinks to occur in not only cancer cells, but also healthy cells. This, in turn, causes both on-target regression of tumor cells, and several unwanted side effects that include nausea, kidney damage, nerve damage, heart failure, and hearing loss. IV administration of cisplatin results in high initial plasma drug levels which rapidly decrease with a half-life of roughly thirty (30) minutes. These plasma concentrations are contrasted with low tumor penetration, which limits the potential overall benefit of the therapeutic intervention. An ideal administration regimen of cisplatin would increase the tumor concentration of the API to maximize chemotherapeutic effects while simultaneously decreasing the plasma drug concentration to decrease unwanted side effects.

Preclinical studies by Shikanov, et al., 2011 illustrate this point. Using a bioresorbable polymer to control the delivery of cisplatin, the study was able to significantly improve therapeutic outcomes in a mouse model of bladder cancer while decreasing systemic exposure to the drug.

Remarkably, administration of cisplatin with the bioresorbable polymer directly into the tumor resulted in a five (5)-fold increase in the maximum tolerated dose (MTD) compared to systemic administration. In addition to increased tolerance of cisplatin, significant improvements in therapeutic outcomes and API distribution were observed. Local tumor injection of the bioresorbable excipient system resulted in 80% of subjects remaining disease-free for forty (40) days (i.e., the remainder of the study). This is in stark contrast to standard systemic administration of cisplatin which resulted in exponential tumor mass growth after seven (7) days. In line with the observed therapeutic benefits, local tumor administration of the bioresorbable excipient system resulted in drug levels at the site of administration over five-hundred (500) times higher than levels observed with systemic administration. Additionally, reverse trends were observed in systemic exposure where local tumor administration of the bioresorbable excipient system resulted in an eighty (80)-fold decrease in plasma drug levels compared to systemic administration. Together, this highlights the potential for polymer/API excipient systems to maximize exposure to the desired site of action, while simultaneously limiting systemic exposure to APIs and potentially decreasing side effects.

Resorbable polymers offered by Poly-Med, Inc. as excipients for drug delivery:

Poly-Med, Inc. (PMI), the leader in bioresorbable materials and medical device development, is vertically integrated with design, development, and manufacturing capabilities. PMI has a growing opportunity for providing materials for drug delivery via PMI’s unique Viscoprene® technology.  Electrospun materials are generated using a combination of the Viscoprene® polymer that forms a base depot for drug delivery with additional polymeric diluents/APIs. Once combined, this drug delivery system can be injected through a standard Luer-Lok needle and syringe to be administered into the desired anatomical location. Additionally, PMI offers a catalog of Viscoprene® polymers, which allows for tailoring of the release properties of the API to meet the necessary clinical treatment schedule.

PMI is able to offer medical device development for medical-grade electrospinning, extrusion, additive manufacturing, and technical processes in a certified ISO Class 8 environment. PMI facilities are certified to meet ISO: 13485:2016 standards for quality management of its design, development, and manufacturing of bioresorbable polymers, fibers, sutures, medical textiles, and biomedical products. Connect with PMI today to acquire more information about the Viscoprene® drug delivery technology to customize the delivery of your active pharmaceutical ingredient of interest by contacting sales@poly-med.com.

Biomedical Textile Spotlight: Braiding Bioresorbables

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At Poly-Med, Inc., we focus on the design, development, and manufacturing of polymeric bioresorbable medical components, devices, and excipients. Our in-house vertically integrated system sets us apart from other competitors and makes us the LEADER OF BIORESORBABLES. We offer a wide variety of integrated solutions, including textile manufacturing of medical-grade braids. With our vertically integrated system, we are able to modify the polymer and yarn that are used to create the technical braid, and then alter the post-processing steps of the braid to yield the desired strength and mechanical parameters.

A common braided medical device is the absorbable suture; these sutures provide temporary support of a wound until the tissue is able to withstand normal physiological stresses. Over time, hydrolysis of the suture leads to the absorption of the implant coupled with the loss of mechanical strength followed by mass loss of the suture. Sutures can be manufactured through braiding, which produces intricate constructs that are created through the intertwining of multiple filaments or yarns forming a singular construct. Producing braided medical devices, such as sutures, is a well-established technique that allows for the structure and mechanical behaviors to be tailored to a targeted application. By changing the braiding pattern and process settings such as pick count, parameters such as strength, kink resistance, and torsion control, can be adjusted to modify the material’s performance.

One of the benefits of our vertical integration system is the ability to oversee the process from polymer through finished device. With our known catalog of polymers (https://www.poly-med.com/solutions/medical-polymers/), we have the ability to easily modify construct properties (strength and mass retention profiles) based on known chemistries. Additionally, we are able to perform custom extrusions to generate varying deniers, filament count, and tenacity.  Multifilaments are often used in braided sutures due to their excellent flexibility, handling properties, and greater knot strength compared to monofilaments. Additionally, coatings can be applied to braids to reduce surface roughness and tissue drag.  The manufacturing process of braiding is an ideal technique to develop bioresorbable sutures due to PMI’s ability to tailor braiding properties to meet the specific needs of medical applications. Contact us today to learn how we can help you with your next braided medical device!

Workhorse Polymers for Bioresorbable Device Development: Max-Prene® 955 and Dioxaprene® 100M

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Continuing the evolution of the bioresorbable medical device market has led to significant growth of the implantable device industry. When considering a bioabsorbable polymer to use for your specific device, many criteria should be considered based on the design requirements and desired functionality of the device’s intended use. Two (2) workhorse polymers that have endured the demand of multiple devices would be our Max-Prene® 955 and Dioxaprene® 100M. These polyester-based polymers have demonstrated their ability to support the need for the most demanding applications through their unique material properties.

Max-Prene® 955 is a fast-degrading, high strength, high stiffness polymer mainly comprised of glycolide with minor segments of  L-lactide. Attributable to its high glycolide content, Max-Prene® 955 allows for a faster crystallization than other glycolide/lactide copolymers, and permits improved processing (faster crystallizing time, higher modulus, and increased degradation profile). Our Max-Prene® 955 polymer typically exhibits strength loss in one to four weeks with complete mass loss occurring in approximately six (6) months (depending on processing format and anatomical location). The Max-Prene® 955 polymer can be processed for a variety of applications, including extruded articles, fiber extrusion (e.g., suture such as Vicryl®), textiles, molded applications, and 3D Printing.

Beyond Max-Prene® 955, Poly-Med offers its Dioxaprene® 100M (PDO linear homopolymer) that can also be processed into a variety of formats similar to applications listed above. Dioxaprene® 100M polymer has a lower initial modulus compared to Max-Prene® 955 and is best utilized for applications looking for extended strength retention, coupled with increased flexibility. PDO based-polymers, (e.g., PDS® II sutures), maintain strength for 4 – 6 weeks with complete mass loss occurring in approximately nine (9) months (depending on processing format and anatomical location).

When selecting a polymer to best fit your device’s need, consider one of the two workhorse polymers (Max-Prene® 955 or Dioxaprene® 100M), which continues to drive innovation in the bioresorbable medical device industry and contact us today to learn more!

Expectations of Working with Poly-Med, Inc.

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Poly-Med is the leader in bioresorbable polymers and customer solutions. We are a vertically integrated company that, thanks to our design and development approach, can design, develop, and manufacture absorbable medical textiles and custom components, providing an adaptable approach to customer needs for any medical application.

To support our development approach and provide support to our vertical integration business structure, Poly-Med, Inc. offers full in-house analytics. We have a vast array of in-house testing equipment that provide a quick and efficient turnaround on the assessment of our clients’ bioresorbable product properties.

There is more to Poly-Med than providing unparalleled expertise and an efficient, structured approach to custom solutions.

At Poly-Med, we try to always go beyond what is expected. All relationships, including and especially those with clients, involve expectations, and conflicts tend to occur when expectations are not met. Our goals are to make excellent impressions and exceed our clients’ basic expectations. We do so by being proactive, dependable, and understanding the importance of keeping commitments. Our clients trust us because they know we will properly develop and follow through on their strategies and support their product and their vision. In addition, we continuously deliver consistency: consistent quality, consistent results, consistent product.

In summary, you can expect:

– Unparalleled expertise
– Dependability
– Reliability
– Collaboration
– Responsiveness
– And, most importantly, we deliver the results.

If you are interested in developing a bioresorbable medical device and want a partner with experience, Contact us for more information!

AP Soliani Ph.D.

Standard Specifications for Surgical Mesh: A Review of FDA Guidance on Surgical Mesh Design

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On March 2, 1999, the U.S. Food and Drug Administration released a guidance document entitled Guidance for the Preparation of a Premarket Notification Application for a Surgical Mesh. Now in 2018, nearly 20 years later, it is still easy to become overwhelmed with everything required to prepare a new device for submission to the FDA. Guidance documents such as this one provide recommendations for the starting points of testing new devices and help alleviate some of the guesswork around what is required and what isn’t. Fortunately, partnering with a company like Poly-Med, with over 25 years of experience in bioresorbable materials and textiles, can help further navigate these waters.

This particular guidance document covers submission guidelines for surgical meshes in a wide variety of applications where a mesh product would be used to reinforce weakened soft tissue. These include area applications in abdominal wall repair (hernia repair), suture line/staple line reinforcement, muscle flap reinforcement, gastric banding, breast reconstruction, pelvic organ prolapse, and many more. For many of these applications, the current market trend is moving toward bioresorbable solutions, providing mechanical support throughout the healing process without permanent synthetic materials in the body. Poly-Med is the leader in bioresorbable textiles and has developed bioresorbable mesh products on the market for a wide variety of applications.

The FDA’s primary interest in any device review can usually be summarized in two words: safety and efficacy. Not surprisingly at all, the guidance document first focuses on the product being safe for human use. Likewise, this is usually a best first-step to consider in product development as future product development will all hinge on the materials as being safe for implantation. With this in this focus, the FDA requires the submission to include description of all material components in the device. This includes at minimum the sources/supplier and purity. To satisfy this requirement, material suppliers can provide reference to device master files (MAF), Certificate of Analysis (CoA), and Safety Data Sheets (SDS) with materials, all of which are noted to help simplify the review process. When considering the materials, special attention should be paid to any materials, reagents, or processing aids which are considered to be potentially cytotoxic, carcinogenic, or immunogenic. Additional testing may be required for any of these materials which are used to air in processing and may remain as residuals in the final material.

The next step in safety of an implantable device is consideration of sterilization. Applications are suggested to specify the method, validations, sterility assurance level (SAL, recommended SAL of 10-6), method for monitoring sterility, and packaging used to maintain sterility. Poly-Med uses several trusted partners with experience in sterilization to coordinate offering these services to our clients. Dependent on the type of material used and the desired processing plan, bioresorbable meshes can be sterilized using irradiation, ethylene oxide, or new emerging technologies such as nitrogen dioxide1.

While many of our materials are used in devices on the market and have proven biocompatibility, it is recommended that biocompatibility testing be conducted on final manufactured, sterilized, and packaged devices, as all can influence the final reaction in the body. While some provisions are allowed for products using the exact same material specifications as another similar device on the market, the guidance generally recommends that applications include testing in accordance to ISO-10993 for Cytotoxicity, Sensitization, Irritation or Intracutaneous Reactivity, Systemic Toxicity (acute), Genotoxicity, Implantation with histology of the surrounding tissue, Hemolysis, and Pyrogenicity. Given that most bioresorbable materials will leave some mass within the body for greater than 30 days, the FDA further recommends testing for Subchronic Toxicity and Chronic Toxicity. These tests should generally be conducted according to relevant USP Class VI and ASTM standards.

When using bioresorbable materials, part of the efficacy claim of a surgical mesh is its ability to degrade over time. In alignment with this guidance, Poly-Med often performs degradation studies for each device developed, being sure to take into account material selection, processing methods, as well as sterilization. Poly-Med is fully capable of conducting in-house in vitro degradation studies in both real and accelerated environments. Accelerated time points are used to quickly identify appropriate time points for a real time study and then evaluate device functionality and specifications at pre-determined time points. For surgical mesh devices, common strength loss tests are dependent on the application, and often include tensile strength, burst strength, suture pull-out strength, and tear resistance.

Though expiration dating is required for all surgical meshes, the need is especially apparent with bioresorbable materials. Many of these materials degrade with exposure to moisture, light, and/or heat, so packaging and sterilization methods can play a critical role in the ultimate shelf-life of the product. This guidance allows for expiration dating to be continuously updated over time without the need for a new 510k submission under the scope of Good Manufacturing Practice (GMP). This allows products to quickly enter the market and then slowly increase the expiration dates of new production as the real-time stability study continues.

If you are interested in developing a bioresorbable surgical mesh and want a partner with experience, Contact us for more information!

Andrew Hargett, M.S.

1 Lambert, B., et al. (2011). AAPS PharmSciTech, 12(4), pp. 1116-1126. doi: 10.1208/s12249-011-9644-8
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225553/

Creating Structure Out of Chaos: Standardization for Fiber-Based Devices

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Poly-Med had the recent opportunity to present at an ASTM Workshop on the Characterization of Fiber-based Scaffolds and Devices in Manchester, NH at the Advanced Regenerative Manufacturing Institute (ARMI) https://www.armiusa.org/. The workshop was organized by ASTM International (http://www.astm.org), the National Institute of Standards and Technology (NIST) https://www.nist.gov/, and hosted by ARMI. The workshop featured seminar discussions from academia, clinicians, and included industrial spotlights on emerging technologies and application of fiber-based scaffolds and the promise they offer for regenerative medicine and medical device applications. Attendees of the workshop were able to discuss how fiber-based scaffolds are able to mimic the mechanics, architecture, and functionality of native tissues, while providing a temporary replacement for new cellular and tissue growth. A key focus of the event was the development of fiber-based scaffold characterization techniques to ensure consistency across facilities and uniformity in construct description and categorization.

Poly-Med presented on the importance of accurate and timely measures of critical release criteria for fiber-based scaffolds. Such criteria are required to ensure that high quality, safe, effective, and consistently reliable products are provided to clinicians. Poly-Med’s extensive work on fiber-based scaffolds and device examples spanned the use of technical textiles (warp knit, weft knit, and braided constructs), as well as the innovative technologies of electrospinning and additive manufacturing. Key areas of interest at this workshop included, image-based analysis approaches reviewing periodicity, porosity (void space), and diffusivity of fiber-based constructs. Method development and release testing were discussed along with batch-to-batch variations and the importance of establishing robust specifications that can be accurately, and reproducibly, measured.

Fiber-based scaffolding continues to be an ideal platform for tissue scaffolds and medical devices, yet still requires superior characterization to be fully utilized across emerging medical therapies. If you are interested in converting your lab-based scaffold into a robust medical device, be sure to contact Poly-Med to learn about our fiber-based methods (https://poly-med.com/solutions/medical-fibers-textiles and our in-house electrospinning capabilities (https://poly-med.com/solutions/regenerative-scaffolding/).

Seth McCullen, Ph.D.

Heat Setting and the Impact on Medical Textiles

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If you’ve ever woken up late for an important job interview or meeting, you’ve probably thrown on some clothes and looked in the mirror with horror at all of the wrinkles staring back at you. While ironing clothes is certainly not one of my favorite chores, something about the heat and steam can totally change the outfit’s look. In medical textiles, this process of heat setting is equally important…and not just to look good in the operating room!

At Poly-Med, Inc., we synthesize very unique polymers for extrusion into fibers/yarns and ultimately for knitting into specialized medical textiles. Though the material coming off of the knitting machine looks somewhat finished, the process to manufacture a useful product is often far from done. One such post-processing technique we use is known as heat setting. Though our materials are medical grade and bioresorbable, the core chemistry at work with heat setting our advanced textiles is the same as with ironing common clothing materials.

The long, polymeric chains in both synthetic clothing and our bioresorbable polymers are able to “stick” together to produce fibers by means of intermolecular forces, namely hydrogen bonds. When exposed to moisture, pressure, and/or temperature, these intermolecular bonds can break, shift, and realign to produce unwanted creases. Even without the externally added forces, internal stresses are introduced throughout processing, such as from the twisting of yarn during spinning or the bending of the yarn during knitting to produce the pattern.

To work around this and remove the internal stresses, the fabric can be heated above the Glass Transition Temperature (Tg), where amorphous regions of the polymer can easily slide around. This temperature is below the Melting Temperature (Tm) and thus does not result in a phase change of the fabric, but merely provides enough energy to break down the intermolecular forces in the amorphous region which previously formed into now undesirable positions. As the material cools back down, the intermolecular forces can stabilize into stress-free conditions for whatever configuration the fabric is currently held in. For clothing with a heavy iron on top of it, the result tends to ‘press’ out the wrinkles and flatten the fabric between the flat ironing board and iron.

It is here, in the actual processing methods, that differences arise for our unique materials. In clothing, a particularly pesky wrinkle can be conquered with the addition of steam and a little elbow grease. The addition of water easily penetrates the amorphous regions of the fibers and acts as a plasticizer or lubricant between the polymeric chains, effectively reducing the material’s Tg to allow the amorphous regions more freedom to move. When the material hydrolytically degrades, as with our bioresorbable polymers, the addition of steam isn’t such a great idea. We instead use dry heat, forced air, and even vacuum chambers to apply heat to the fabric and still avoid degradation or strength loss. Heat Setting by these means further allows us to use custom fixtures and presses to hold the fabric in place as it cools, producing flat as well as 3D fabric forms. While this does make the medical textiles look great, the process often improves function as well, improving handle-ability for downstream processing and end-use, allowing the construct to conform to a unique shape, providing dimensional stability, and also increasing temperature resistance.

Though bioresorbable polymers pose a few unique challenges for heat setting, Poly-Med is very experienced in unique solutions for both small and large scale projects. If you are interested in post-processing of medical textiles or you are working on a medical device and are interested in learning more about bioresorbable polymers, Contact us at sales@poly-med.com to learn how we can advance your idea.

Andrew Hargett, M.S.