Dataset Information

Immunomodulatory ECM-like Microspheres for Accelerated Bone Regeneration in Diabetes Mellitus.

ABSTRACT: Bone repair and regeneration process is markedly impaired in diabetes mellitus (DM) that affects hundreds of millions of people worldwide. As a chronic inflammatory disease, DM creates a proinflammatory microenvironment in defective sites. Most of the studies on DM-associated bone regeneration, however, neglect the importance of immunomodulation under the DM condition and adopt the same approaches to normal bone healing, leading to limited bone healing. In this study, we developed a unique bioinspired injectable microsphere as an osteoimmunomodulatory biomaterial that modulates macrophages to create a prohealing microenvironment under the DM condition. The microsphere was self-assembled with heparin-modified gelatin nanofibers, and interleukin 4 (IL4) was incorporated into the nanofibrous heparin-modified gelatin microsphere (NHG-MS). IL4 has binding domains with heparin, and the binding of IL4 to heparin stabilizes this cytokine, protects it from denaturation and degradation, and subsequently prolongs its sustained release to modulate macrophage polarization. The IL4-loaded NHG-MS switched the proinflammatory M1 macrophage into a prohealing M2 phenotype, recovered the M2/M1 ratio to a normal level, efficiently resolved the inflammation, and ultimately enhanced osteoblastic differentiation and bone regeneration. The development of osteoimmunomodulatory biomaterials that harness the power of macrophages for immunomodulation, therefore, is a novel and promising strategy to enhance bone regeneration under DM condition.

SUBMITTER: Hu Z

PROVIDER: S-EPMC6437671 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Immunomodulatory ECM-like Microspheres for Accelerated Bone Regeneration in Diabetes Mellitus.

Hu Zhiai Z Ma Chi C Rong Xin X Zou Shujuan S Liu Xiaohua X

ACS applied materials & interfaces 20180108 3

Bone repair and regeneration process is markedly impaired in diabetes mellitus (DM) that affects hundreds of millions of people worldwide. As a chronic inflammatory disease, DM creates a proinflammatory microenvironment in defective sites. Most of the studies on DM-associated bone regeneration, however, neglect the importance of immunomodulation under the DM condition and adopt the same approaches to normal bone healing, leading to limited bone healing. In this study, we developed a unique bioin ...[more]

PMID: 29280610

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Project description:Diabetes mellitus (DM) affects hundreds of million people worldwide and the impaired bone healing is an important DM-related complication. Understanding how DM affects the activities of osteoclasts and the underlying mechanisms is crucial to the development of effective approaches for accelerating bone healing in DM condition. To date, however, the influence of DM on osteoclasts remains obscure and controversial. In this study, we established a type 2 DM (T2DM) alveolar bone defect model, which closely simulates the pathogenesis of human T2DM, to explore the diabetic osteoclast activity during bone regeneration. We found that a high glucose concentration diminished the formation of osteoclasts, and the differentiation and function of osteoclasts from T2DM rats were suppressed. The degradation of matrix by osteoclasts was significantly reduced at a high glucose concentration. In vivo experiments further indicated that T2DM inhibited osteoclastogenesis and osteoclast activity, and delayed the degradation of matrix during the alveolar bone regeneration in T2DM rats. Our work clarifies the influence of T2DM on osteoclasts, and provides valuable insights for the design of novel scaffolding materials that target on osteoclasts for T2DM bone regeneration. STATEMENT OF SIGNIFICANCE: Impaired bone healing is one of the diabetes mellitus (DM)-related complications. Understanding how DM affects osteoclast activity and scaffolding matrix degradation is pivotal to the development of effective approaches for accelerating bone healing in DM condition. Currently, the influences of DM on osteoclast activity and matrix degradation in bone defect areas, however, remain controversial and obscure. Herein, we established a type 2 DM (T2DM) alveolar bone defect model and our results show that T2DM inhibited osteoclastogenesis and osteoclast activity, and delayed the degradation of scaffolding matrix. Our work clarifies the influence of T2DM on osteoclasts and matrix degradation, and provides insights for the design of novel scaffolding materials that target on osteoclasts for T2DM bone regeneration.

Dataset Information

Immunomodulatory ECM-like Microspheres for Accelerated Bone Regeneration in Diabetes Mellitus.

Publications

Immunomodulatory ECM-like Microspheres for Accelerated Bone Regeneration in Diabetes Mellitus.

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