Biomaterials (biostable and biodegradable) for use in the development of medical devices and drug delivery devices can be polymeric, biologic, metallic, ceramic or their composites, each presenting unique biocompatibility and thrombogenicity characteristics (if in blood contact). Biocompatibility testing is typically addressed in FDA guidance documents and ISO 10993 biocompatibility standards. The concept of biocompatibility is moving from a “do no harm” mission (i.e., nontoxic, nonantigenic, nonmutagenic, etc.) to one of doing “good,” that is, encouraging positive healing responses. These new devices will promote the formation of normal healthy tissue, as well as the integration of the device into adjacent tissue. In some contexts, biocompatibility can become a disruptive technology that can change therapeutic paradigms (e.g., drug-coated stents). The new generation of implantable and tissue engineered medical devices control biologic interactions by use of bioactive, therapeutic, smart and nano-enabled materials to improve safety and efficacy. Additionally, there is an emerging trend to use the biomechanics of the device in soft tissue and in cardiovascular applications to control outcomes.
With the emergence of combination products, a paradigm shift is occurring that incorporates biocompatibility as part of the functional requirements of the device. Many of these devices are “combination” drug or biologic devices resulting in new regulatory challenges. This current era requires rapid development cycles leading, in many cases, to first-in-man evaluation as part of the exit strategy. The medical and controlled drug delivery expertise at Exponent can be applicable to help understand the challenges and risks being faced during the development phases.
Exponent’s Capabilities
Exponent has a wide range of expertise in areas relating to biocompatibility testing, including:
- Toxicity and biocompatibility of a wide range of organic and inorganic compounds, including metals of various alloys
- Toxicity and biocompatibility of biomaterials
- Toxicity and fate of nano-materials and particulates
- Toxicity and biocompatibility of materials and residues on multiple-use units after reprocessing/resterilization
- Device-related infection control strategies and associated regulatory support
- Injury to cardiovascular, pulmonary and orthopaedic tissues
- Design, implementation, and characterization of mechanically active (2D and 3D) culture devices
- Characterization of individual cell, cell population, and tissue response to the mechanical environment
- Characterization of cells and tissues to the mechanical environment through:
- Mechanical testing
- Assaying for matrix protein accumulation
- Measurement of radiolabel incorporation to determine matrix protein biosynthesis
- Real-time quantitative RT-PCR to determine gene expression
- Real-time physiologic measures using fluorescent intra- and extracellular probes
- Subcellular protein localization studies
- Characterization of protein changes in response to the mechanical environment through:
- ELISAs (enzyme-linked immunosorbent assays)
- Western blotting and immunochemical assays
- Measurement of enzyme activity
- Biochemical assays
- Human embryonic stem-cell culture and general culture techniques for clonal and primary cells
- Characterization of undifferentiated human embryonic stem cell proliferation
- Characterization of cellular responses to soluble factor gradients (2D and 3D); cell migration assays and autocrine/paracrine interactions
- Assay development Design of co-culture systems within 2D and 3D environments (hydrogels, polymers, and biomatrices)
- Culture of cells in 2D and 3D (in tissue- and cell-seeded gel environments)
- Epifluorescent microscopy techniques, including confocal microscopy
- Microscale transport phenomena, computational modeling, and biological MEMS
- Evaluation and determination of transport parameters for therapeutic agents eluted from biomaterials and devices
- Assessment of corrosion (such as general, pitting (ASTM F2129), galvanic (ASTM G71) and fretting), degradation, and toxicity of materials in long-term implants or particulates left in situ after surgical procedure. Measurement of metal release rate as a function of time (metal leaching rate) for long-term implants. Biokinetic modeling of metal release from metallic implants.
- Intellectual property support for cases involving biocompatibility of medical devices.
Exponent’s Device Experience
Spinal fixation devices
- Joint replacements
- Stents for cardiovascular, neurovascular, biliary, carotid , tracheal-bronchial, and other applications
- Annuloplasty rings
- Central venous catheters and ports
- Cardiovascular occlusion devices
- Pacemakers
- Heart valves
- Vena cava filters
- Pacemakers and leads
- Implantable cardioverter-defibrillators (ICDs)
- Drug delivery systems
- Implantable electromagnetic transponders
- Implantable cardioverter-defibrillators (ICDs)
Combination devices
- Ocular shunts
- Dental implants
- Hernia meshes
- Urogynecological devices
- Breast implants
- Ocular pharmaceutical
- Urinary catheters
- Laparoscopic, endoscopic, and colonoscopic devices
- Laparascopic surgical cutting tools
- Radiographic shields during surgery
- Battery cases
- Electrodes and control unit
- Medical socks with anti-infective
Additional Materials
View an animation of coronary stent deployment. This animation shows the insertion and deployment of multiple stents in a long coronary artery occlusion.
Download the presentation slides from Heart Rhythm 2009: "Fourteen-Year Trends in Pacemaker Implantation in the United States."