An investigation of scavenger receptor A mediated leukocyte binding to polyanionic and uncharged polymer hydrogels.

Cell adhesion to biomaterials can be mediated in part by mechanisms aside from the traditionally recognized opsinization and integrin binding mechanisms. In this study, we investigated the role of scavenger receptor A (SR-A) in leukocyte binding to a series of well-controlled polyanionic and uncharged hydrogels based on a poly(N-isopropylacrylamide) backbone. The hydrogels were injected in the peritoneal cavity of SR-A knockout (KO) and wild-type mice using a minimally invasive procedure and allowed to set in situ.

Transient inhibition of connective tissue infiltration and collagen deposition into porous poly(lactic-co-glycolic acid) discs.

Connective tissue rapidly proliferates on and around biomaterials implanted in vivo, which impairs the function of the engineered tissues, biosensors, and devices. Glucocorticoids can be utilized to suppress tissue ingrowth, but can only be used for a limited time because they nonselectively arrest cell proliferation in the local environment. The present study examined use of a prolyl-4-hydroxylase inhibitor, 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), to suppress connective tissue ingrowth in porous PLGA discs implanted in the peritoneal cavity for 28 days.

The recognition of biomaterials: pattern recognition of medical polymers and their adsorbed biomolecules.

All biomedical materials are recognized as foreign entities by the host immune system despite the substantial range of different materials that have been developed by material scientists and engineers. Hydrophobic biomaterials, hydrogels, biomaterials with low protein binding surfaces, and those that readily adsorb a protein layer all seem to incite similar host responses in vivo that may differ in magnitude, but ultimately result in encapsulation by fibrotic tissue. The recognition of medical materials by the host is explained by the very intricate pattern recognition system made up of integrins, toll-like receptors, scavenger receptors, and other surface proteins that enable leukocytes to perceive almost any foreign body.

Biomaterials as vaccine adjuvants.

Biomaterials are promising candidate adjuvants to enhance vaccine efficacy. Through adjuvant design, we can broaden the use of vaccines to diseases such as AIDS, malaria, and cancer. This review addresses the fundamentals of vaccine and adjuvant function in order to determine guidelines for adjuvant design, including aspects of the vaccine such as disease target, antigen formulation, and delivery route.

Biomaterials, fibrosis, and the use of drug delivery systems in future antifibrotic strategies.

All biomaterials, when implanted into the body, elicit an inflammatory response that evolves into fibrovascular tissue formation on and around the material. As a result, material scientists and tissue engineers should be concerned about host response to tissue-engineered constructs that have a biomaterial component, because the host response to this component will interfere with device function and reduce the lifespan of tissue engineering devices in vivo. The fibrotic response to biomaterials is not unlike pathological fibrosis of the liver, lung, kidney, and peritoneum in many ways: i) the presence of mononuclear leukocytes are common in the local environment of both pathological fibrosis and biomaterial-induced fibrosis even though cells of mesenchymal origin are responsible for laying the majority of the extracellular matrix; ii) paracrine-signaling molecules, such as transforming growth factor beta;1, are essential mediators of fibrosis, whether it is pathological or biomaterial induced; and iii) injury and/or the presence of foreign materials (including bacterial components, toxins, or man-made objects) are essential initiators for the development of the fibrotic response.

Assays on the influence of biomaterials on allogeneic rejection in tissue engineering.

In tissue engineering, innate responses to biomaterial scaffolds will affect rejection of allogeneic cells. Biomaterials directly influence innate and adaptive immune cell adhesion, reactive oxygen intermediate production, cytokine secretion, nuclear factor-kappa B nuclear translocation, gene expression, and cell surface markers, all of which are likely to affect allogeneic rejection responses. A major goal in tissue engineering is to induce transplant tolerance, potentially by manipulating the biomaterial component.

Effect of alginate on innate immune activation of macrophages.

Alginate, a natural polysaccharide, has been widely used in tissue engineering and drug delivery, but like other biomaterials, it causes inflammation by unknown mechanisms. We hypothesized that alginate would stimulate innate immune responses through macrophage receptors. In this study, we showed that sodium alginate induced activation of macrophage-like cells (RAW264.

Effects of biomaterial-induced inflammation on fibrosis and rejection.

Evidence is emerging that biomaterials cause inflammation by ligating innate immune receptors on antigen presenting cells. Although inflammation is usually viewed as detrimental, it has unexpected and potentially beneficial effects on fibrosis and transplant rejection. For example, the magnitude of inflammation due to a biomaterial is not predictive of the extent of fibrosis.

Suppressed splenocyte proliferation following a xenogeneic skin graft due to implanted biomaterials.

Background: Immune system responses to antigens in the context of biomaterials are poorly understood. Biomaterial implantation results in an inflammatory reaction, which is anticipated to alter the adaptive immune response, in the case presented here, to a skin xenograft. Our earlier work showed unexpectedly low splenocyte proliferation following a xenogeneic cell implant in tandem with a biomaterial in the form of a microcapsule.

In vivo recognition by the host adaptive immune system of microencapsulated xenogeneic cells.

Background: Microencapsulation is under consideration as a means of enabling pancreatic islet transplantation. To understand better the ongoing destructive host response, we examined whether the adaptive immune system of the recipient recognized polymer-encapsulated xenogeneic cells implanted intraperitoneally.

Methods: Balb/c mice were implanted with xenogeneic Chinese hamster ovary cells, inside and outside poly(hydroxyethyl methacrylate-methyl methacrylate) microcapsules, and responses were compared with xenografted Chinese hamster skin (positive control).