Fracture healing is accelerated in the absence of the adaptive immune system

Toben, D.; Schroeder, I.; Khassawna, T.N. El; Mehta, Manav; Hoffmann, Jan‐Erik; Frisch, J.; Schell, Hanna; Lienau, Jasmin; Serra, Alessandro; Radbruch, Andreas; Khassawna, Thaqif El; Duda, Georg N.

doi:10.1016/j.bone.2010.04.220

Cited by 42 publications

(60 citation statements)

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“…Furthermore, the enrichment of gene expression, in aged mice, approximating that of LPS stimulated macrophages is consistent with an underlying basal inflammatory state often associated with aging. Similarly, in aged 20 DPF fractures, we detected enrichment of CD8+ T cells, which has been shown to negatively impact bone regeneration (21,27) . We also found differential immunological pathway activation between age groups at 0 DPF and 20 DPF, which further supports the difference in activity of immune cells between young adult and old mice (Supp Table 3).…”

Section: Discussionmentioning

confidence: 68%

Bone healing in an aged murine fracture model is characterized by sustained callus inflammation and decreased cell proliferation

Hebb

Ashley

McDaniel

et al. 2017

Journal Orthopaedic Research

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Section: Discussionmentioning

confidence: 68%

Bone healing in an aged murine fracture model is characterized by sustained callus inflammation and decreased cell proliferation

Hebb

Ashley

McDaniel

et al. 2017

Journal Orthopaedic Research

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“…In some tissues this would lead to poor regeneration; however, in bone, an absence of neutrophils and macrophages may not adversely affect tissue repair. 34,35 Macrophages have different phenotypes depending on the local tissue environment; the classically activated M1 phenotype is present during acute inflammation and is linked to upregulation of proinflammatory cytokines and enzymes, such as inducible nitric oxide synthase (iNOS). During tissue regeneration, macrophages transition to an anti-inflammatory M2 phenotype that plays a role in dampening inflammation by the production of anti-inflammatory cytokines, such as IL-10 and IL-1ra.…”

Section: Delivery Of Diclofenac From Plga/peg Scaffolds Discussionmentioning

confidence: 99%

Investigation of Localized Delivery of Diclofenac Sodium from Poly(D,L-Lactic Acid-co-Glycolic Acid)/Poly(Ethylene Glycol) Scaffolds Using anIn VitroOsteoblast Inflammation Model

Sidney

Heathman

Britchford

et al. 2015

Tissue Engineering Part A

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Nonunion fractures and large bone defects are significant targets for osteochondral tissue engineering strategies. A major hurdle in the use of these therapies is the foreign body response of the host. Herein, we report the development of a bone tissue engineering scaffold with the ability to release anti-inflammatory drugs, in the hope of evading this response. Porous, sintered scaffolds composed of poly(D,L-lactic acid-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) were prepared with and without the anti-inflammatory drug diclofenac sodium. Analysis of drug release over time demonstrated a profile suitable for the treatment of acute inflammation with ∼80% of drug released over the first 4 days and a subsequent release of around 0.2% per day. Effect of drug release was monitored using an in vitro osteoblast inflammation model, comprised of mouse primary calvarial osteoblasts stimulated with proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ). Levels of inflammation were monitored by cell viability and cellular production of nitric oxide (NO) and prostaglandin E2 (PGE2). The osteoblast inflammation model revealed that proinflammatory cytokine addition to the medium reduced cell viability to 33%, but the release of diclofenac sodium from scaffolds inhibited this effect with a final cell viability of ∼70%. However, releasing diclofenac sodium at high concentrations had a toxic effect on the cells. Proinflammatory cytokine addition led to increased NO and PGE2 production; diclofenac-sodium-releasing scaffolds inhibited NO release by ∼64% and PGE2 production by ∼52%, when the scaffold was loaded with the optimal concentration of drug. These observations demonstrate the potential use of PLGA/PEG scaffolds for localized delivery of anti-inflammatory drugs in bone tissue engineering applications.

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“…While endochondral bone regeneration is the primary mechanism of fracture repair, depletion of macrophages also impacts osteogenesis during intramembranous healing . Similarly, the absence of T and B lymphocytes and neutrophils also alters fracture healing …”

Section: Inflammatory Phase—inflammatory Cellsmentioning

confidence: 99%

Cellular biology of fracture healing

Bahney

Zondervan²,

Allison³

et al. 2018

Journal Orthopaedic Research

321

353

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The biology of bone healing is a rapidly developing science. Advances in transgenic and gene-targeted mice have enabled tissue and cell-specific investigations of skeletal regeneration. As an example, only recently has it been recognized that chondrocytes convert to osteoblasts during healing bone, and only several years prior, seminal publications reported definitively that the primary tissues contributing bone forming cells during regeneration were the periosteum and endosteum. While genetically modified animals offer incredible insights into the temporal and spatial importance of various gene products, the complexity and rapidity of healing— coupled with the heterogeneity of animal models—renders studies of regenerative biology challenging. Herein, cells that play a key role in bone healing will be reviewed and extracellular mediators regulating their behavior discussed. We will focus on recent studies that explore novel roles of inflammation in bone healing, and the origins and fates of various cells in the fracture environment.

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Fracture healing is accelerated in the absence of the adaptive immune system

Cited by 42 publications

References 0 publications

Bone healing in an aged murine fracture model is characterized by sustained callus inflammation and decreased cell proliferation

Bone healing in an aged murine fracture model is characterized by sustained callus inflammation and decreased cell proliferation

Investigation of Localized Delivery of Diclofenac Sodium from Poly(D,L-Lactic Acid-co-Glycolic Acid)/Poly(Ethylene Glycol) Scaffolds Using anIn VitroOsteoblast Inflammation Model

Cellular biology of fracture healing

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