Biomaterials as we know them today had their origins in the late 1940s with off-the-shelf commercial polymers and metals. The evolution of materials for medical applications from these simple origins ...has been rapid and impactful. This review relates some of the early history; addresses concerns after two decades of development in the twenty-first century; and discusses how advanced technologies in both materials science and biology will address concerns, advance materials used at the biointerface, and improve outcomes for patients.
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.
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.
Display omitted
Surface-induced thrombosis is still a significant clinical concern for many types of blood-contacting medical devices. In particular, protein adsorption and platelet adhesion are important events due ...to their ability to trigger the coagulation cascade and initiate thrombosis. Poly(lactic acid) (PLA) has been the predominant polymer used for making bioresorbable stents. Despite long-term advantages, these stents are associated with higher rates of early thrombosis compared with permanent metallic stents. To address this issue, we modified the surface of PLA with a perfluoro compound facilitated by surface activation using radio frequency (RF) plasma. Fluoropolymers have been extensively used in blood contacting materials, such as blood vessel replacements due to their reduced thrombogenicity and reduced platelet reactivity. The compositions of plasma-treated surfaces were determined by electron spectroscopy for chemical analysis (ESCA). Also, contact angle measurements, cell cytotoxicity and the degradation profile of the treated polymers are presented. Finally, relevant blood compatibility parameters, including plasma protein adsorption, platelet adhesion and morphology, were evaluated. We hypothesized that tight binding of adsorbed albumin by fluoropolymers enhances its potential for blood-contacting applications.
Although bioresorbable stents made from poly(lactic acid) (PLA) may have long-term clinical advantages, they have shown higher rates of early thrombosis as compared with permanent metallic stents. To improve the thromboresistance of PLA, we developed a novel method for surface fluorination of this polymer with a perfluoro compound. Fluoropolymers (e.g., expanded polytetrafluoroethylene) have long been used in blood-contacting applications due to their satisfactory clinical performance. This is the first report of PLA surface fluorination which might be applied to the fabrication of a new generation of fluorinated PLA stents with improved platelet interaction, tunable degradability and drug release capabilities. Also, we describe a general strategy for improving the platelet interactions with biomaterials based on albumin retention.
Biologic scaffolds are derived from mammalian tissues, which must be decellularized to remove cellular antigens that would otherwise incite an adverse immune response. Although widely used ...clinically, the optimum balance between cell removal and the disruption of matrix architecture and surface ligand landscape remains a considerable challenge. Here we describe the use of time of flight secondary ion mass spectroscopy (ToF-SIMS) to provide sensitive, molecular specific, localized analysis of detergent decellularized biologic scaffolds. We detected residual detergent fragments, specifically from Triton X-100, sodium deoxycholate and sodium dodecyl sulphate (SDS) in decellularized scaffolds; increased SDS concentrations from 0.1% to 1.0% increased both the intensity of SDS fragments and adverse cell outcomes. We also identified cellular remnants, by detecting phosphate and phosphocholine ions in PAA and CHAPS decellularized scaffolds. The present study demonstrates ToF-SIMS is not only a powerful tool for characterization of biologic scaffold surface molecular functionality, but also enables sensitive assessment of decellularization efficacy.
We report here on the use of a highly sensitive analytical technique, time of flight secondary ion mass spectroscopy (ToF-SIMS) to characterize detergent decellularized scaffolds. ToF-SIMS detected cellular remnants and residual detergent fragments; increased intensity of the detergent fragments correlated with adverse cell matrix interactions. This study demonstrates the importance of maintaining a balance between cell removal and detergent disruption of matrix architecture and matrix surface ligand landscape. This study also demonstrates the power of ToF-SIMS for the characterization of decellularized scaffolds and capability for assessment of decellularization efficacy. Future use of biologic scaffolds in clinical tissue reconstruction will benefit from the fundamental results described in this work.
PDF
