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.

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.

Absorbable 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.

Poly-Med is a Vertically Integrated Bioresorbable Medical Device Manufacturing Partner:

Manufacturing bioabsorbable medical devices is hard. Controlling moisture levels and material degradation through the production cycle requires specialized equipment and process controls to ensure quality of finished devices. In contrast to other bioresorbable polymer manufacturers, Poly-Med produces polymer, is able to extrude this material to desired monofilament or multifilament formats, and is able process this material via warp knitting, weft knitting, or braiding processes to produce custom biomedical textiles. Beyond traditional textiles, we can process our bioresorbable polymers into non-woven formats via electrospinning via our state-of-the-art electrospinning facility. In addition to accessing Poly-Med’s more than thirty (30) years of experience manufacturing bioresorbable polymers, partnering with Poly-Med simplifies your bioresorbable medical device manufacturing supply chain. Contact us to today begin developing your custom bioresorbable medical device product line with a trusted partner for manufacturing advanced bioresorbable medical devices or purchase off-the-shelf high-performance bioresorbable polymers!

At Poly-Med (PMI), we pride ourselves in being a “one-stop shop”, providing medical grade materials and processing services at our facilities. PMI is a trusted leader in the production of bioresorbable polymers suitable for our client’s needs. We have a variety of polymers that covers a wide range of physical and mechanical properties. Additionally, PMI is an expert on the processing of bioresorbable polymers via extrusion, technical textiles, electrospinning, as well as additive manufacturing processes.  

One of the key components Poly-Med specializes in is film production by either solvent processing or melt-extrusion.  Films have been extensively used as implantable medical devices as barrier applications in general surgery, wound care, and dental products.  Solvent processing of films is used for highly specialized products where heat sensitive materials can also be incorporated.  Solvent processing is able to incorporate multiple materials, layers within the final film construct, and care is often used in the full characterization of solvent processed films to ensure all residuals are removed to an acceptable level.  

Despite the advantages of solvent processing, melt-extrusion is a more industry standard for creation of film substrates.  Melt-extrusion involves the process of melting and metering polymer through a die to achieve the desired thickness and width dimensions upon quenching. Based on the material properties, downstream equipment such as roller systems are put in place to process the film appropriately.  Key components of the film extrusion lines are polymer feeders, extruder with a proper screw design screw, filtration system, die, quenching equipment, roller assembly, winder, and measurement equipment.

Film extrusion field is divided into two (2) categories: 1) cast, or flat film extrusion and 2) blown film. For the flat film extrusion, a die is used to direct the flow of melted polymer into a dimension controlled film. Several aspects need to be considered when setting the die gap distance such as polymer swelling, collector, and desired dimensions. It is critical to ensure constant and uniform flow of the polymer across the area of the die. The downstream equipment such as roller systems are used to ensure that the final product meets the client’s specifications. Typical film specification includes dimensions, texture, uniformity, and material molecular weight among others. Specifications must be clearly defined based on the final product functionality. 

At PMI, our engineers work diligently to identify the balance between process and final product characteristics.  Based on the polymer’s properties and product specifications, process parameters are developed to ensure the constant flow of the polymer and proper quenching of the final product. This ensures that the material is stable to either be used as the final component or be processed based on the client’s needs.

PMI specializes in contract manufacturing of components using medical grade polymers. With PMI’s vertically integrated structure, our diverse team of experts supports our clients from the initial phases of device conception and prototype development to manufacturing by providing in-house device development, project management, quality assurance, and analytical testing. Following process validations and regulatory clearance, PMI provides manufacturing services, inspection plans with validated test methods, packaging, and schedule deliveries to our clients worldwide. Our PMI team is committed to providing high quality products at a reasonable cost through constant process improvement to production lines. Connect with PMI today to hear more about our product offerings and design, development, and analytical capabilities! If you are interested in hearing more about how Poly- Med can help advance your idea and medical product conception, please contact us here.

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 bioresorbable 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!

Poly-Med is the leader in bioresorbable polymers and custom solutions. We are vertically integrated based on our ability to provide absorbable polymer, fiber, and mesh through the design and development process, and can manufacture these absorbable devices and components for any medical application.

To support our development approach and provide support to our vertically integrated 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.

By working with Poly-Med, 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!