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Individualized plasticity autograft mimic with efficient bioactivity inducing osteogenesis.

ABSTRACT: Mineralized tissue regeneration is an important and challenging part of the field of tissue engineering and regeneration. At present, autograft harvest procedures may cause secondary trauma to patients, while bone scaffold materials lack osteogenic activity, resulting in a limited application. Loaded with osteogenic induction growth factor can improve the osteoinductive performance of bone graft, but the explosive release of growth factor may also cause side effects. In this study, we innovatively used platelet-rich fibrin (PRF)-modified bone scaffolds (Bio-Oss^®) to replace autograft, and used cytokine (BMP-2) to enhance osteogenesis. Encouragingly, this mixture, which we named "Autograft Mimic (AGM)", has multiple functions and advantages. (1) The fiber network provided by PRF binds the entire bone scaffold together, thereby shaping the bone grafts and maintaining the space of the defect area. (2) The sustained release of BMP-2 from bone graft promoted bone regeneration continuously. (3) AGM recruited bone marrow mesenchymal stem cells (BMSCs) and promote their proliferation, migration, and osteogenic differentiation. Thus, AGM developed in this study can improve osteogenesis, and provide new guidance for the development of clinical bone grafts.

SUBMITTER: Wei Y

PROVIDER: S-EPMC8041815 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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Individualized plasticity autograft mimic with efficient bioactivity inducing osteogenesis.

Wei Yan Y Zhu Guixin G Zhao Zifan Z Yin Chengcheng C Zhao Qin Q Xu Hudi H Wang Jinyang J Zhang Jinglun J Zhang Xiaoxin X Zhang Yufeng Y Xia Haibin H

International journal of oral science 20210412 1

Mineralized tissue regeneration is an important and challenging part of the field of tissue engineering and regeneration. At present, autograft harvest procedures may cause secondary trauma to patients, while bone scaffold materials lack osteogenic activity, resulting in a limited application. Loaded with osteogenic induction growth factor can improve the osteoinductive performance of bone graft, but the explosive release of growth factor may also cause side effects. In this study, we innovative ...[more]

PMID: 33846295

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Project description:BackgroundOsteogenesis imperfecta (OI) is a rare disease leading to hereditary bone fragility. Nearly 90% of cases are caused by mutations in the collagen genes COL1A1/A2 (classical OI) leading to multiple fractures, scoliosis, short stature and nonskeletal findings as blue sclera, hypermobility of joints, bone pain and delayed motor function development. Bisphosphonates are used in most moderate and severely affected patients assuming that an increase of bone mineral density might reduce fractures and bone pain in patients with OI. Denosumab as a RANK ligand antibody inhibiting osteoclast maturation has been approved for osteoporosis treatment in adults. First data from small clinical trials promised a high efficacy of Denosumab in children with OI. Aim of this analysis was a retrospective evaluation of an individualized biomarker-associated treatment regime with Denosumab in 10 children with classical OI which were followed for 1 year after their participation in a pilot trial with Denosumab. Therefore urinary deoxypyridinoline levels were evaluated frequently as an osteoclastic activity marker and depending on that levels Denosumab injections were scheduled individually.MethodsTen patients (age range: 6.16-12.13 years; all participated in the former OI-AK phase 2 trial (NCT01799798)) were included in the follow-up period. Denosumab was administered subcutaneously depending on the individual urinary excretion course of deoxypyridinoline (DPD/Crea) as osteoclastic activity marker with 1 mg/kg body weight. DPD/Crea levels were evaluated before denosumab administration and afterwards. If patients present after an initial decrease after injection with a re-increase up to the DPD/crea level before Denosumab injection next dosage was planned. Changes of areal bone mineral density (aBMD) using dual energy x-ray absorptiometry of the lumbar spine after 12 month was evaluated. Safety was assessed by bone metabolism markers and side effect reporting.ResultsDuring follow-up mean relative change of lumbar aBMD was - 6.4%. Lumbar spine aBMD z-Scores decreased from - 1.01 ± 2.61 (mean ± SD) to - 1.91 ± 2.12 (p = 0.015). Mobility changed not significantly (GMFM-88 -6.49 ± 8.85% (p = 0.08). No severe side effects occurred. Dose intervals could be extended in the mean from 12 weeks previously to 20.3 weeks.ConclusionsOn average, it was possible to prolong the intervals between drug administrations and to reduce the total dose about by 25% without a decrease of mobility or change of vertebral shape despite a reduction of lumbar aBMD during 1 year of biomarker-directed Denosumab treatment. Further trials are necessary to balance side effects and highest efficacy in children.

Project description:BackgroundInjectable bone cement is commonly used in clinical orthopaedics to fill bone defects, treat vertebral compression fractures, and fix joint prostheses during joint replacement surgery. Poly(propylene fumarate) (PPF) has been proposed as a biodegradable and injectable alternative to polymethylmethacrylate (PMMA) bone cement. Recently, there has been considerable interest in two-dimensional (2D) black phosphorus nanomaterials (BPNSs) in the biomedical field due to their excellent photothermal and osteogenic properties. In this study, we investigated the biological and physicochemical qualities of BPNSs mixed with PPF bone cement created through thermal cross-linking.MethodsPPF was prepared through a two-step process, and BPNSs were prepared via a liquid phase stripping method. BP/PPF was subsequently prepared through thermal cross-linking, and its characteristics were thoroughly analysed. The mechanical properties, cytocompatibility, osteogenic performance, degradation performance, photothermal performance, and in vivo toxicity of BP/PPF were evaluated.ResultsBP/PPF exhibited low cytotoxicity levels and mechanical properties similar to that of bone, whereas the inclusion of BPNSs promoted preosteoblast adherence, proliferation, and differentiation on the surface of the bone cement. Furthermore, 200 BP/PPF demonstrated superior cytocompatibility and osteogenic effects, leading to the degradation of PPF bone cement and enabling it to possess photothermal properties. When exposed to an 808-nm laser, the temperature of the bone cement increased to 45-55 °C. Furthermore, haematoxylin and eosin-stained sections from the in vivo toxicity test did not display any anomalous tissue changes.ConclusionBP/PPF exhibited mechanical properties similar to that of bone: outstanding photothermal properties, cytocompatibility, and osteoinductivity. BP/PPF serves as an effective degradable bone cement and holds great potential in the field of bone regeneration.

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Individualized plasticity autograft mimic with efficient bioactivity inducing osteogenesis.

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Individualized plasticity autograft mimic with efficient bioactivity inducing osteogenesis.

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