Long-term controlled delivery of rhBMP-2 from collagen–hydroxyapatite scaffolds for superior bone tissue regeneration

Quinlan, Elaine; Thompson, Emmet M.; Matsiko, Amos; O’Brien, Fergal J.; López-Noriega, Adolfo

doi:10.1016/j.jconrel.2015.03.028

Cited by 112 publications

(102 citation statements)

References 39 publications

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“…With the development of bone tissue engineering, scaffolds fabricated using different biomaterials, such as bioactive glasses, polylactic acid, collagen, chitosan, and hydroxyapatite (HA), have been explored for bone regeneration due to their biocompatibility, sufficient supply, and no secondary damage for patients. [1][2][3][4][5][6][7] Among these biomaterials, type 1 9 To date, mixing collagen with minerals and mineralizing collagen have been used to modify collagen scaffolds for simulating the composition and microstructure of bone tissue to the greatest extent possible. [10][11][12][13][14][15][16][17] Because HA is a primary mineral component of natural bone and possesses outstanding bioactivity, osteoconductivity, biocompatibility with bone cells, good mechanical properties, and a slow degradation rate in vivo, it has often been the first choice for modifying collagen scaffolds.…”

Section: Introductionmentioning

confidence: 99%

Synergistic intrafibrillar/extrafibrillar mineralization of collagen scaffolds based on a biomimetic strategy to promote the regeneration of bone defects

Wang¹,

Manh²,

Wang³

et al. 2016

IJN

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The mineralization of collagen scaffolds can improve their mechanical properties and biocompatibility, thereby providing an appropriate microenvironment for bone regeneration. The primary purpose of the present study is to fabricate a synergistically intra- and extrafibrillar mineralized collagen scaffold, which has many advantages in terms of biocompatibility, biomechanical properties, and further osteogenic potential. In this study, mineralized collagen scaffolds were fabricated using a traditional mineralization method (ie, immersed in simulated body fluid) as a control group and using a biomimetic method based on the polymer-induced liquid precursor process as an experimental group. In the polymer-induced liquid precursor process, a negatively charged polymer, carboxymethyl chitosan (CMC), was used to stabilize amorphous calcium phosphate (ACP) to form nanocomplexes of CMC/ACP. Collagen scaffolds mineralized based on the polymer-induced liquid precursor process were in gel form such that nanocomplexes of CMC/ACP can easily be drawn into the interstices of the collagen fibrils. Scanning electron microscopy and transmission electron microscopy were used to examine the porous micromorphology and synergistic mineralization pattern of the collagen scaffolds. Compared with simulated body fluid, nanocomplexes of CMC/ACP significantly increased the modulus of the collagen scaffolds. The results of in vitro experiments showed that the cell count and differentiated degrees in the experimental group were higher than those in the control group. Histological staining and micro-computed tomography showed that the amount of new bone regenerated in the experimental group was larger than that in the control group. The biomimetic mineralization will assist us in fabricating a novel collagen scaffold for clinical applications.

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Section: Introductionmentioning

confidence: 99%

Synergistic intrafibrillar/extrafibrillar mineralization of collagen scaffolds based on a biomimetic strategy to promote the regeneration of bone defects

Wang¹,

Manh²,

Wang³

et al. 2016

IJN

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“…44,45 These results may be partially explained by the observation that sustained release of BMP-2 can enhance the long-term osteogenesis and migration of progenitor cells or mesenchymal stem cells for several weeks; these processes are necessary for successful new bone formation. 46 Growth factors are inactivated easily by storage at different temperatures and for different durations; however, few studies have been performed to assess the bioactivities of growth factors that were loaded onto delivery systems for bone regeneration. In 1 study, 60% of the bioactivity of growth factors absorbed on a Ca-P cement scaffold was preserved after storage at room temperature for 5 weeks.…”

mentioning

confidence: 99%

Dose reduction of bone morphogenetic protein-2 for bone regeneration using a delivery system based on lyophilization with trehalose

Zhang¹,

Yu²,

Wang³

et al. 2018

IJN

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Introduction To induce sufficient new bone formation, high doses of bone morphogenetic protein-2 (BMP-2) are applied in regenerative medicine that often induce serious side effects. Therefore, improved treatment strategies are required. Here, we investigate whether the delivery of BMP-2 lyophilized in the presence of trehalose reduced the dose of BMP-2 required for bone regeneration. Materials and methods A new growth factor delivery system was fabricated using BMP-2-loaded TiO 2 nanotubes by lyophilization with trehalose (TiO 2 -Lyo-Tre-BMP-2). We measured BMP-2 release characteristics, bioactivity, and stability, and determined the effects on the osteogenic differentiation of bone marrow stromal cells in vitro. Additionally, we evaluated the ability of this formulation to regenerate new bone around implants in rat femur defects by micro-computed tomography (micro-CT), sequential fluorescent labelling, and histological analysis. Results Compared with absorbed BMP-2-loaded TiO 2 nanotubes (TiO 2 -BMP-2), TiO 2 -Lyo-Tre-BMP-2 exhibited sustained release, consistent bioactivity, and higher stability of BMP-2, and resulted in greater osteogenic differentiation of BMSCs. Eight weeks post-operation, TiO 2 -Lyo-Tre-BMP-2 nanotubes, with various dosages of BMP-2, regenerated larger amounts of new bone than TiO 2 -BMP-2 nanotubes. Conclusion Our findings indicate that delivery of BMP-2 lyophilized with trehalose may be a promising method to reduce the dose of BMP-2 and avoid the associated side effects.

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“…3 Normal bone morphogenetic protein 2 (BMP2) is an important protein component that is involved in the maintenance of the structure and function of cartilage. 4 BMP2 expression significantly increases during cartilage damage. 5 Thus, it is an important function of BMP2 to maintain the formation of articular cartilage and repair damaged cartilage.…”

Section: Introductionmentioning

confidence: 97%

Continuous release of bone morphogenetic protein-2 through nano-graphene oxide-based delivery influences the activation of the NF-κB signal transduction pathway

Zhong¹,

Feng²,

Lin³

et al. 2017

IJN

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Graphene oxide (GO) has been used as a delivery vehicle for small molecule drugs and nucleotides. To further investigate GO as a smart biomaterial for the controlled release of cargo molecules, we hypothesized that GO may be an appropriate delivery vehicle because it releases bone morphogenetic protein 2 (BMP2). GO characterization indicated that the size distribution of the GO flakes ranged from 81.1 nm to 45,749.7 nm, with an approximate thickness of 2 nm. After BMP2 adsorption onto GO, Fourier-transformed infrared spectroscopy (FTIR) and thermal gravimetric analysis were performed. Compared to GO, BMP2-GO did not induce significant changes in the characteristics of the materials. GO continuously released BMP2 for at least 40 days. Bone marrow stem cells (BMSCs) and chondrocytes were treated with BMP2-GO in interleukin-1 media and assessed in terms of cell viability, flow cytometric characterization, and expression of particular mRNA. Compared to GO, BMP2-GO did not induce any significant changes in biocompatibility. We treated osteoarthritic rats with BMP2 and BMP2-GO, which showed significant differences in Osteoarthritis Research Society International (OARSI) scores ( P <0.05). Quantitative assessment revealed significant differences compared to that using BMP2 and BMP2-GO ( P <0.05). These findings indicate that GO may be potentially used to control the release of carrier materials. The combination of BMP2 and GO slowed the progression of NF-κB-activated degenerative changes in osteoarthritis. Therefore, we infer that our BMP2-GO strategy could alleviate the NF-κB pathway by inducing continuous BMP2 release.

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Long-term controlled delivery of rhBMP-2 from collagen–hydroxyapatite scaffolds for superior bone tissue regeneration

Cited by 112 publications

References 39 publications

Synergistic intrafibrillar/extrafibrillar mineralization of collagen scaffolds based on a biomimetic strategy to promote the regeneration of bone defects

Synergistic intrafibrillar/extrafibrillar mineralization of collagen scaffolds based on a biomimetic strategy to promote the regeneration of bone defects

Dose reduction of bone morphogenetic protein-2 for bone regeneration using a delivery system based on lyophilization with trehalose

Continuous release of bone morphogenetic protein-2 through nano-graphene oxide-based delivery influences the activation of the NF-κB signal transduction pathway

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Long-term controlled delivery of rhBMP-2 from collagen–hydroxyapatite scaffolds for superior bone tissue regeneration

Cited by 112 publications

References 39 publications

Synergistic intrafibrillar/extrafibrillar mineralization of collagen scaffolds based on a biomimetic strategy to promote the regeneration of bone defects

Synergistic intrafibrillar/extrafibrillar mineralization of collagen scaffolds based on a biomimetic strategy to promote the regeneration of bone defects

Dose reduction of bone morphogenetic protein-2 for bone regeneration using a delivery system based on lyophilization with trehalose

Continuous release of bone morphogenetic protein-2 through nano-graphene oxide-based delivery influences the activation of the NF-&kappa;B signal transduction pathway

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Continuous release of bone morphogenetic protein-2 through nano-graphene oxide-based delivery influences the activation of the NF-κB signal transduction pathway