We devised a novel nerve prosthesis composed of an elastomeric gelatinous tube and multifilament gelatinous fibers, both of which were prepared from styrene-derivatized gelatin, which allows in situ formation of a bioactive substance-incorporated gel. An in vitro study showed that the axonal regeneration potential of a photocured gelatin layer impregnated with laminin, fibronectin, and NGF was almost comparable with that of coated Matrigel. A nerve conduit and fibers prepared from photoreactive gelatin was subjected to visiblelight irradiation with rotation in the presence of camphorquinone as a photoinitiator using a custom-designed apparatus. A sample of transparent gelatinous conduit with an inner diameter of 1.2 mm and a wall thickness of 0.6 mm and gelatin fibers ranging from 10 to 100 µm in diameter were produced. The photocured elastomeric gelatinous tube was flexible and had structural integrity that allowed mechanical handling without breaking. A novel nerve guidance prosthesis composed of tubes packed with fibers was assembled. This photofabrication technology may enable the design of a tailor-made shape and rapid morphogenesis and functional recovery of damaged nerve tissue.
Summary
Bisphosphonates distributed to bone exert toxic effects specifically towards osteoclasts. On the other hand, intravenous administration of a nitrogen‐containing bisphosphonate (N‐BP) such as zoledronate induces acute‐phase reactions (APRs), including influenza‐like fever 1 day later, indicating an interaction with immunocompetent cells circulating blood. Although it has been reported that activation of γδ T cells is pivotal to induce an APR following treatment with zoledronate, downstream events, including the production of inflammatory cytokines after activation of γδ T cells, remain obscure. We investigated the effects of zoledronate on inflammatory cytokine expression in human peripheral blood mononuclear cells (PBMCs) in vitro. While zoledronate induced mRNA expressions of tumour necrosis factor‐α (TNF‐α), interleukin (IL)‐1β, IL‐6 and interferon‐γ (IFN‐γ) in PBMC, depletion of γδ T cells abolished that zoledronate‐induced expression of those cytokines, indicating the necessity of γδ T cells for expression induction by zoledronate. However, which types of cells were responsible for the production of those cytokines in blood remained unclear. As it is generally accepted that monocytes and macrophages are primary sources of inflammatory cytokines, CD14+ cells from PBMC were exposed to zoledronate in the presence of PBMC, which resulted in induced expression of mRNAs for IL‐1β, IL‐6 and IFN‐γ, but not for TNF‐α. These results indicate that CD14+ cells are responsible, at least in part, for the production of IL‐1β, IL‐6 and IFN‐γ in blood exposed to zoledronate. This suggests that CD14+ cells play an essential role in the occurrence of APRs following N‐BP administration.
During vertebrate development, neural crest cells arise in the dorsal region of the fusing neural tube, then migrate extensively across the embryonic body to differentiate into various cell types. In adults, subsets of neural crest‐derived cells (NCDCs) reside as stem cells and are considered useful as cell sources for autologous cell therapy. Previous studies have suggested that these NCDC subsets persist into adulthood in mammals, especially those within dentofacial compartments. We have found NCDCs in a wide variety of tissues, including palate, gingiva, and tongue, as well as hair follicles, submandibular glands, and buccal mucosa in adult mice. NCDCs from buccal mucosa can also form neurosphere‐like structures that have a capability to differentiate into osteoblasts. These findings indicate that NCDCs reside in various adult oral and dentofacial regions, and possess potential to differentiate into osteoblastic cells, thus suggesting that those in adults may be a useful source for bone regeneration strategies. In recent years, several researchers have reported regeneration experiments using NCDCs obtained from oral and dentofacial tissues. Here, we review findings related to the distribution of NCDCs, with focus on the oral and dentofacial regions, as well as the future prospects of NCDC‐based regenerative therapies.
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