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Osteoinductive biodegradable intramedullary implant accelerates bone healing and mitigates complications in a rat bone transport model

ABSTRACT: Osteoinductive biodegradable intramedullary implant accelerates bone healing and mitigates complications in a rat bone transport model

PROVIDER: PRJNA824864 | ENA |

REPOSITORIES: ENA

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Osteoinductive biodegradable intramedullary implant accelerates bone healing and mitigates complications in a rat bone transport model

Project description:Bone transport distraction osteogenesis (DO) is one of the most successful surgery-driven endogenous tissue regeneration approaches for the treatment of large bone defects. However, prolonged consolidation, docking site nonunion, and pin tract infection remain challenging complications. Here, we engineered an osteoinductive, biodegradable intramedullary (IM) implant for sustained release of bone morphogenetic protein-2 (BMP-2) as an adjunctive therapy of bone transport to address the clinical challenges. A hybrid tissue engineering construct (HyTEC) technique was developed to enable sustained release of BMP-2 in a broad range. 100% bony fusion was achieved in the IM implants incorporating with 2 μg and 6 μg BMP-2 as early as 34 days after bone transport surgeries in the management of 8-mm femoral defect. Load bearing was restored 55 days after surgeries when the fixator was removed. Eluting BMP-2 from the IM implants accelerates bone formation and angiogenesis at early phase, and increase mineralization at late phase, especially at the docking sites, leading to early bony bridging. Moreover, no pin tract infection but seamless integration could be found in the 2 μg and 6 μg BMP-2 treated groups. Surgical control and IM implant showed high proportion of non-union and pin tract infections. 2 μg BMP-2 delivered by collagen sponge or 0.5 μg BMP-2-laden IM implant did not induce bone regeneration effectively, resulting in some non-unions and infections. A presence of bacteria of fecal origin in the infection sites was identified. In conclusion, this osteoinductive IM implant holds great promise in revolutionizing bone transport DO technique in the management of bone defect by accelerating bone regeneration and mitigating complications.

2023-06-09 | GSE200518 | GEO

Transcriptomic profile of Lin negative, LEPR positive cells of murine peri-implant fibrous tissue and peri-implant bone

Project description:To investigate the transcriptomic profile difference between LEPR cells in peri-implant fibrous tissue and peri-implant bone

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Transcriptomic profile of Lin negative, LEPR positive cells of human peri-implant fibrous tissue and peri-implant bone

Project description:Peri-implant fibrosis is one of the most common reasons for implant failure and surgical revision after prosthetic joint replacement. This type of surgical revisionis associated with substantial additional morbidity and healthcare costs. However, the cellular and molecular mediators of peri-implant fibrosis remain unclear. Here, we show that peri-implant fibrotic tissue in mice and humans is largely composed of a specific population of leptin receptor-expressing(LEPR+) cells and that these LEPR+cells are necessary and sufficient to both generate and maintain peri-implant fibrotic tissue. Genetic ablation of LEPR+cells prevents peri-implant fibrosis, and implantation of LEPR+cells from peri-implant fibrotic tissue is sufficient to induce fibrosis in secondary hosts. We further identify adhesion G protein-coupled receptorF5 (ADGRF5) as a crucial mediator of the fibrotic response by LEPR+cells, as conditional deletion of ADGRF5 in LEPR+cells attenuates peri-implant fibrosis while augmenting peri-implant bone formation. Finally, we demonstrate that inhibition of ADGRF5 by intra articular or systemic administration of neutralizing anti-ADGRF5prevents and reverses peri-implant fibrosis. Thus, pharmaceutical agents that inhibit the ADGRF5 pathway inLEPR+cells may represent a new approach to prevent and treat peri-implant fibrosis.

2024-03-10 | GSE227128 | GEO

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A tantalum-containing zirconium-based metallic glass with superior endosseous implant relevant properties (HUVEC)

Project description:Tantalum (Ta) metal is well known for its ideal corrosion resistance and biological effects as endosseous implants. However, the metal has a elastic modulus as high as 186GPa which is not comparable to the natural bone (10-40GPa), and it also has a relative high cost. Here, to fully exploit the advantages of Ta as endosseous implants, a small amount of Ta (as low as 3 at.%) was successfully added into a zirconium-based metallic glass (MG) to generate an advanced functional endosseous implant, Zr58Cu25Al14Ta3 MG, with superior comprehensive properties. Upon carefully dissecting the surface chemistry and atomic structure, the results show that amorphization of Ta enable the uniform distribution in material surface, leading to a significantly improved chemical stability and extensive material-cell contact regulation. Systematical analyses on the immunological, angiogenesis and osteogenesis capability of the material is carried out by utilizing the next-generation sequencing, revealing that Zr58Cu25Al14Ta3 MG can regulate angiogenesis through VEFG signaling pathway and osteogenesis via BMP signaling pathway. Animal experiment further confirms a sound osseointegration of Zr58Cu25Al14Ta3 MG in achieving better bone-implant-contact and inducing faster peri-implant bone formation.

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A tantalum-containing zirconium-based metallic glass with superior endosseous implant relevant properties (BMSC)

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Comparison of the gene expression of periimplantitis affected peri-implant tissue and healthy peri-implant tissue in vivo in human.

Project description:In this study we want to ascertain the differences and similarities of infected and inflammated peri implant tissue versus healthy peri implant tissue at the mRNA level.

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Thrombopoietic Agents: Novel Osteoinductive Agents for Bone Healing

Project description:Thrombopoietic Agents: Novel Osteoinductive Agents for Bone Healing

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