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Injectable hydrogel systems with multiple biophysical and biochemical cues for bone regeneration.

ABSTRACT: Bone regeneration is a complex process in which angiogenesis and osteogenesis are crucial. Introducing multiple angiogenic and osteogenic cues simultaneously into a single system and tuning these cues to optimize the niche remains a challenge for bone tissue engineering. Herein, based on our injectable biomimetic hydrogels composed of silk nanofibers (SNF) and hydroxyapatite nanoparticles (HA), deferoxamine (DFO) and bone morphogenetic protein-2 (BMP-2) were loaded on SNF and HA to introduce more angiogenic and osteogenic cues. The angiogenesis and osteogenesis capacity of injectable hydrogels could be regulated by tuning the delivery of DFO and BMP-2 independently, resulting in vascularization and bone regeneration in cranial defects. The angiogenesis and osteogenesis outcomes accelerated the regeneration of vascularized bones toward similar composition and structure to natural bones. Therefore, the multiple biophysical and chemical cues provided by the nanofibrous structures, organic-inorganic compositions, and chemical and biochemical angiogenic and osteogenic inducing cues suggest the potential for clinical applicability of these hydrogels in bone tissue engineering.

SUBMITTER: Cheng W

PROVIDER: S-EPMC7204512 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Injectable hydrogel systems with multiple biophysical and biochemical cues for bone regeneration.

Cheng Weinan W Ding Zhaozhao Z Zheng Xin X Lu Qiang Q Kong Xiangdong X Zhou Xiaozhong X Lu Guozhong G Kaplan David L DL

Biomaterials science 20200501 9

Bone regeneration is a complex process in which angiogenesis and osteogenesis are crucial. Introducing multiple angiogenic and osteogenic cues simultaneously into a single system and tuning these cues to optimize the niche remains a challenge for bone tissue engineering. Herein, based on our injectable biomimetic hydrogels composed of silk nanofibers (SNF) and hydroxyapatite nanoparticles (HA), deferoxamine (DFO) and bone morphogenetic protein-2 (BMP-2) were loaded on SNF and HA to introduce mor ...[more]

PMID: 32215404

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Project description:Currently, bone infections caused by diseases or injuries are a major health issue. In addition, the conventional therapeutic approaches used to treat bone diseases or injuries present several drawbacks. In the area of tissue engineering, researchers have been developing new alternative therapeutic approaches, such as scaffolds, to promote the regeneration of injured tissues. Despite the advantages of these materials, most of them require an invasive surgical procedure. To overcome these problems, the main focus of this work was to develop scaffolds for bone regeneration, which can be applied using injectable hydrogels that circumvent the use of invasive procedures, while allowing for bone regeneration. Throughout this work, injectable hydrogels were developed based on a natural polymer, dextran, along with the use of two inorganic compounds, calcium β-triphosphate and nanohydroxyapatite, that aimed to reinforce the mechanical properties of the 3D mesh. The materials were chemically characterized considering the requirements for the intended application: the swelling capacity was evaluated, the degradation rate in a simulated physiological environment was assessed, and compression tests were performed. Furthermore, vancomycin was incorporated into the polymeric matrices to obtain scaffolds with antibacterial performance, and their drug release profile was assessed. The cytotoxic profile of the hydrogels was assessed by an MTS assay, using osteoblasts as model cells. The data obtained demonstrated that dextran-based hydrogels were successfully synthesized, with a drug release profile with an initial burst between 50 and 80% of the drug. The hydrogels possess fair biocompatibility. The swelling capacity showed that the stability of the samples and their degradation profile is compatible with the average time period required for bone regeneration (usually about one month) and have a favorable Young's modulus (200-300 kPa). The obtained hydrogels are well-suited for bone regeneration applications such as infections that occur during implantation or bone graft substitutes with antibiotics.

Project description:Injectable hydrogel is suitable for the repair of lacunar bone deficiency. This study fabricated an injectable, self-adaptive silk fibroin/mesoporous bioglass/sodium alginate (SMS) composite hydrogel system. With controllable and adjustable physical and chemical properties, the SMS hydrogel could be easily optimized adaptively to different clinical applications. The SMS hydrogel effectively showed great injectability and shapeability, allowing defect filling with no gap. Moreover, the SMS hydrogel displayed self-adaptability in mechanical reinforcement and degradation, responsive to the concentration of Ca2+ and inflammatory-like pH value in the microenvironment of bone deficiency, respectively. In vitro biological studies indicated that SMS hydrogel could promote osteogenic differentiation of bone marrow mesenchymal stem cells by activation of the MAPK signaling pathway. The SMS hydrogel also could improve migration and tube formation of human umbilical vein endothelial cells. Investigations of the crosstalk between osteoblasts and macrophages confirmed that SMS hydrogel could regulate macrophage polarization from M1 to M2, which could create a specific favorable environment to induce new bone formation and angiogenesis. Meanwhile, SMS hydrogel was proved to be antibacterial, especially for gram-negative bacteria. Furthermore, in vivo study indicated that SMS could be easily applied for maxillary sinus elevation, inducing sufficient new bone formation. Thus, it is convincing that SMS hydrogel could be potent in a simple, minimally invasive and efficient treatment for the repair of lacunar bone deficiency. Graphical abstract Image 1 Highlights • Mesoporous bioglass was used as the crosslinking agent and in-situ porogen to form a porous injectable hydrogel.• The composite hydrogel had suitable injectability and self-adaptability for lacunar bone regeneration.• The composite hydrogel can simultaneously regulate macrophage polarization and osteogenic differentiation.

Dataset Information

Injectable hydrogel systems with multiple biophysical and biochemical cues for bone regeneration.

Publications

Injectable hydrogel systems with multiple biophysical and biochemical cues for bone regeneration.

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