To evaluate the role of CCR2 in allergic asthma, mutant mice deficient in CCR2 (CCR2−/−) and intact mice were sensitized with i.p. OVA with alum on days 0 and 7, and challenged by inhalation with nebulization of either OVA or saline. Airway hyperreactivity, measured by the methacholine-provoked increase in enhanced pause, was significantly increased (p < 0.05) in OVA-challenged CCR2−/− mutant mice, compared with comparably challenged CCR2+/+ mice. OVA-challenged CCR2−/− mutants also were also found to have enhanced bronchoalveolar lavage fluid eosinophilia, peribronchiolar cellular cuffing, and Ig subclass switching, with increase in OVA-specific IgG1 and IgE. In addition, RNase protection assay revealed increased whole lung expression of IL-13 in OVA-challenged CCR2−/− mutants. Unexpectedly, serum monocyte chemotactic protein-1 levels were 8-fold higher in CCR2−/− mutants than in CCR2+/+ mice sensitized to OVA, but OVA challenge had no additional effect on circulating monocyte chemotactic protein-1 in either genotype. Ag stimulation of lymphocytes isolated from OVA-sensitized CCR2 mutants revealed a significant increase (p < 0.05) in IL-5 production, which differed from OVA-stimulated lymphocytes from sensitized CCR2+/+ mice. These experiments demonstrate an enhanced response in airway reactivity and in lung inflammation in CCR2−/− mutant mice compared with comparably sensitized and challenged CCR2+/+ mice. These observations suggest that CC chemokines and their receptors are involved in immunomodulation of atopic asthma.

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The natural biopolymers, collagen and alginate, have been widely used in various tissue regeneration procedures. However, their low mechanical and osteoinductive properties represent major limitations of their usage as bone tissue regenerative scaffolds. To overcome these deficiencies, biomimetic composite scaffolds were prepared using a mixture of collagen and alginate as a matrix material, and various silica weight fractions as a coating agent. The composite scaffolds were highly porous (porosity > 78%) and consisted of interconnected pores, with a mesh-like structure (strut diameter: 342-389 mm; average pore size: 468-481 mm). After incubation in a simulated body fluid, various levels of bone-like hydroxyapatite (HA) on the surface of the composite scaffolds developed in proportion to the increase in the silica content coating the scaffolds, indicating that the composite scaffolds have osteoinductive properties. The composite scaffolds were characterised in terms of various physical properties (water absorption, biodegradation and mechanical properties, etc.) and biological activities (cell viability, live/ dead cells, DAPI/phalloidin analysis, osteogenic gene expression, etc.) using pre-osteoblasts (MC3T3-E1).The mechanical improvement (compressive modulus) of a composite scaffold in compressive mode was $2.4-fold in the dry state compared to the collagen/alginate scaffold. Cell proliferation on the composite scaffold was significantly improved by $1.3-fold compared to the mineralised collagen/ alginate scaffold (control). Osteocalcin levels of the composite scaffold after 28 days in cell culture were significantly enhanced by 3.2-fold compared with the control scaffold. These results suggest that mineralised biomimetic composite scaffolds have potential for use in hard tissue regeneration.

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