Abstract The biomaterials community has been unable to accurately assign the term “blood compatible” to a biomaterial in spite of 50 years of intensive research on the subject. There is no clear ...consensus as to which materials are “blood compatible.” There are no standardized methods to assess blood compatibility. Since we use millions of devices in contact with blood each year, it is imperative we give serious thought to this intellectual catastrophe. In this perspective, I consider five hypotheses as to why progress has been slow in evolving a clear understanding of blood compatibility: Hypothesis 1—It is impossible to make a blood compatible material. Hypothesis 2—We do not understand the biology behind blood compatibility. Hypothesis 3—We do not understand how to test for or evaluate blood compatibility. Hypothesis 4—Certain materials of natural origin seem to show better blood compatibility but we do not know how to exploit this concept. Hypothesis 5—We now have better blood compatible materials but the regulatory and economic climate prevent adoption in clinical practice.
Abstract The host response to biomaterials has been studied for decades. Largely, the interaction of host immune cells, macrophages in particular, with implanted materials has been considered to be a ...precursor to granulation tissue formation, the classic foreign body reaction, and eventual encapsulation with associated negative impacts upon device functionality. However, more recently, it has been shown that macrophages, depending upon context dependent polarization profiles, are capable of affecting both detrimental and beneficial outcomes in a number of disease processes and in tissue remodeling following injury. Herein, the diverse roles played by macrophages in these processes are discussed in addition to the potential manipulation of macrophage effector mechanisms as a strategy for promoting site-appropriate and constructive tissue remodeling as opposed to deleterious persistent inflammation and scar tissue formation.
The foreign body reaction (FBR) to implanted materials is of critical importance when medical devices require biological integration and vascularization to support their proper function (e.g., ...transcutaneous devices, implanted drug delivery systems, tissue replacements, and sensors). One class of materials that improves FBR outcomes is made by sphere-templating, resulting in porous structures with uniform, interconnected 34
μ
m pores. With these materials we observe reduced fibrosis and increased vascularization. We hypothesized that improved healing is a result of a shift in macrophage polarization, often measured as the ratio of M1 pro-inflammatory cells to M2 pro-healing cells. In this study, macrophage polarity of 34
μ
m porous implants was compared to non-porous and 160
μ
m porous implants in subcutaneous mouse tissue. Immunohistochemistry revealed that macrophages in implant pores displayed a shift towards an M1 phenotype compared to externalized cells. Macrophages in 34
μ
m porous implants had up to 63% greater expression of M1 markers and up to 85% reduction in M2 marker expression (
p
< 0.05). Macrophages immediately outside the porous structure, in contrast, showed a significant enrichment in M2 phenotypic cells. This study supports a role for macrophage polarization in driving the FBR to implanted materials.
The performance of implantable biomedical devices is impeded by the foreign-body reaction, which results in formation of a dense collagenous capsule that blocks mass transport and/or electric ...communication between the implant and the body. No known materials or coatings can completely prevent capsule formation. Here we demonstrate that ultra-low-fouling zwitterionic hydrogels can resist the formation of a capsule for at least 3 months after subcutaneous implantation in mice. Zwitterionic hydrogels also promote angiogenesis in surrounding tissue, perhaps owing to the presence of macrophages exhibiting phenotypes associated with anti-inflammatory, pro-healing functions. Thus, zwitterionic hydrogels may be useful in a broad range of applications, including generation of biocompatible implantable medical devices and tissue scaffolds.
Since its inception just over a half century ago, the field of biomaterials has seen a consistent growth with a steady introduction of new ideas and productive branches. This review describes where ...we have been, the state of the art today, and where we might be in 10 or 20 years. Herein, we highlight some of the latest advancements in biomaterials that aim to control biological responses and ultimately heal. This new generation of biomaterials includes surface modification of materials to overcome nonspecific protein adsorption in vivo, precision immobilization of signaling groups on surfaces, development of synthetic materials with controlled properties for drug and cell carriers, biologically inspired materials that mimic natural processes, and design of sophisticated three-dimensional (3-D) architectures to produce well-defined patterns for diagnostics, e.g., biological microelectromechanical systems (bioMEMs), and tissue engineering.
The recently commissioned Linac Coherent Light Source is an X-ray free-electron laser at the SLAC National Accelerator Laboratory. It produces coherent soft and hard X-rays with peak brightness ...nearly ten orders of magnitude beyond conventional synchrotron sources and a range of pulse durations from 500 to <10 fs (10-15 s). With these beam characteristics this light source is capable of imaging the structure and dynamics of matter at atomic size and timescales. The facility is now operating at X-ray wavelengths from 22 to 1.2 A and is presently delivering this high-brilliance beam to a growing array of scientific researchers. We describe the operation and performance of this new 'fourth-generation light source'.
Despite intensive surgical excision, radiation therapy, and chemotherapy, the current life expectancy for patients diagnosed with glioblastoma multiforme is only 12 to 15months. One of the approaches ...being explored to increase chemotherapeutic efficacy is to locally deliver chemotherapeutics encapsulated within degradable, polymeric microspheres. This review describes the techniques used to formulate drug encapsulated microspheres targeted for intracranial tumor therapy and how microsphere characteristics such as drug loading and encapsulation efficiency can be tuned based on formulation parameters. Further, the results of in vitro studies are discussed, detailing the varied drug release profiles obtained and validation of drug efficacy. Finally, in vivo results are summarized, highlighting the study design and the effectiveness of the drug encapsulated microspheres applied intracranially.
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