Biomaterials used in medical devices can be polymeric, biologic, metallic, ceramic or composites, each presenting with different biocompatibility characteristics, and hemocompatibility responses for blood-contacting materials. The evaluation of the biocompatibility of a biomaterial is typically addressed by testing outlined in FDA guidance documents and ISO 10993 biocompatibility standards. The concept of biocompatibility has evolved from “inert" (i.e., non-toxic, non-antigenic, non-mutagenic, etc.) to "bioactive," that is, encouraging positive healing responses by actively interacting with the tissue. Biocompatibility is defined by the performance requirements of the biomaterial for a specific device application. Bioactive materials will promote the formation of normal healthy tissue, as well as the integration of the device into adjacent tissue. The new generation of implantable and tissue engineered medical devices control biological interactions by use of pharmacological agents, bioactive coatings or nano-enabled materials to improve safety and efficacy.
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. The medical device and combination products expertise at Exponent can be helpful in understanding the challenges and risks being faced during the device development phases.
Exponent has a wide range of expertise in areas relating to biocompatibility testing, including:
- Toxicity and biocompatibility of
- Biomaterials, including metals, polymers, ceramics, composites, and biological materials
- Nano-materials and particulates
- Materials and residues on multiple-use units after reprocessing/resterilization
- Device-related infection control strategies and associated regulatory support
- Characterization of cells and tissues to the mechanical environment through:
- Mechanical testing
- Assaying for matrix protein accumulation
- Real-time quantitative RT-PCR to determine gene expression
- Real-time physiologic measures using fluorescent intra- and extracellular probesCharacterization of protein changes in response to the mechanical environment through:
- ELISAs (enzyme-linked immunosorbent assays)
- Measurement of enzyme activity
- Biochemical assays
- Characterization of cellular responses to soluble factor gradients (2D and 3D); cell migration assays and autocrine/paracrine interactions
- Epifluorescent microscopy techniques, including confocal microscopy
- Corrosion and Toxicity
- 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 remaining in situ after surgical procedures.
- 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.
- Quantify blood damage
- Blood flow through cardiovascular devices for design evaluation.
- Understanding of the complex interaction of cardiovascular flow dynamics with the function and complications of prosthetic devices
- 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
- Cardiovascular occlusion devices
- Heart valves
- Vena cava filters
- Pacemakers (leads and generators)
- Implantable cardioverter-defibrillators (ICDs) (leads and generators)
- Drug delivery systems
- Allograft implants (vascular, pericardial, dermis, skin, ligaments etc)
- Combination devices
- Implantable electromagnetic transponders
- Ocular shunts
- Dental implants
- Hernia and pelvic meshes
- Urogynecological devices
- Breast implants
- Ocular devices
- Urinary and IV catheters
- Laparoscopic, endoscopic, and colonoscopic devices
- Laparascopic surgical cutting tools
- Radiographic shields during surgery
- Battery cases
- Electrodes and control units
- Medical socks with anti-infective coatings.