Collagen Implants Equipped with ’Fish Scale‘-Like Nanoreservoirs of Growth Factors for Bone Regeneration

Eap, Sandy; Ferrand, Alice; Schiavi, Jessica; Keller, Laetitia; Kökten, Tunay; Fioretti, Florence; Mainard, Didier; Ladam, Guy; Benkirane‐Jessel, Nadia

doi:10.2217/nnm.13.122

Cited by 34 publications

(25 citation statements)

References 45 publications

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“…Recently, we reported that it is possible to incorporate active growth factors (BMP-2, TGF-β1) as nanoreservoirs to induce bone formation. 20,21,[44][45][46] We have also shown that electrospun thin PCL membranes (50 μm) increase the speed of bone regeneration when they incorporate BMP-2 within nanocontainers. We also showed no passive uncontrolled release of those growth factors from the active nanocontainers, but an active cell contact-dependent release.…”

mentioning

confidence: 80%

A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration

Eap¹,

Keller²,

Schiavi³

et al. 2015

IJN

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New-generation implants focus on robust, durable, and rapid tissue regeneration to shorten recovery times and decrease risks of postoperative complications for patients. Herein, we describe a new-generation thick nanofibrous implant functionalized with active containers of growth factors and stem cells for regenerative nanomedicine. A thick electrospun poly(ε-caprolactone) nanofibrous implant (from 700 μm to 1 cm thick) was functionalized with chitosan and bone morphogenetic protein BMP-7 as growth factor using layer-by-layer technology, producing fish scale-like chitosan/BMP-7 nanoreservoirs. This extracellular matrix-mimicking scaffold enabled in vitro colonization and bone regeneration by human primary osteoblasts, as shown by expression of osteocalcin, osteopontin, and bone sialoprotein (BSPII), 21 days after seeding. In vivo implantation in mouse calvaria defects showed significantly more newly mineralized extracellular matrix in the functionalized implant compared to a bare scaffold after 30 days’ implantation, as shown by histological scanning electron microscopy/energy dispersive X-ray microscopy study and calcein injection. We have as well bifunctionalized our BMP-7 therapeutic implant by adding human mesenchymal stem cells (hMSCs). The activity of this BMP-7-functionalized implant was again further enhanced by the addition of hMSCs to the implant (living materials), in vivo, as demonstrated by the analysis of new bone formation and calcification after 30 days’ implantation in mice with calvaria defects. Therefore, implants functionalized with BMP-7 nanocontainers associated with hMSCs can act as an accelerator of in vivo bone mineralization and regeneration.

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mentioning

confidence: 80%

A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration

Eap¹,

Keller²,

Schiavi³

et al. 2015

IJN

Self Cite

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“…In addition to the bioaffinity of ECM components, the architecture of ECM microenvironments also plays a pivotal role in directly modulating GF activity and cell fate during tissue repair (Figure 1c3). Eap et al 49 constructed biomimetic ECM nanostructures for the immobilization of BMP-2 by assembling polysaccharides (chitosan) on collagen nanofibers. Both in vitro and in vivo evaluations confirmed that this sophisticated strategy enhanced the safety and efficacy of the therapeutic matrix in terms of bone formation compared to the more simplistic, traditional approaches based on immersion of the substrates with GFs.…”

Section: Ecm-inspired Gf Delivery Systemsmentioning

confidence: 99%

Novel biomaterial strategies for controlled growth factor delivery for biomedical applications

et al. 2017

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Growth factors (GFs) are soluble proteins secreted by cells that have the ability to regulate a variety of cellular processes and tissue regeneration. However, their translation into clinical applications is limited due to their short effective half-life, low stability, and rapid inactivation by enzymes under physiological conditions. To maximize the effectiveness of GFs and their biologically relevant applicability, a wide variety of sophisticated bio-inspired systems have been developed that augment tissue repair and cellular regeneration by controlling how much, when, and where GFs are released. Recently, protein immobilization techniques combined with nanomaterial carriers have shown promise in mimicking the natural healing cascade during tissue regeneration by augmenting the delivery and effectiveness of GFs. This review evaluates the latest techniques in direct immobilization and relevant biomaterials used for GF loading and release, including synthetic polymers, albumin, polysaccharides, lipids, mesoporous silica-based nanoparticles (NPs), and polymeric capsules. Specifically, we focus on GF-encapsulated NPs in functionalized microporous scaffolds as a promising alternative with the ability to mimic extracellular matrix (ECM) hierarchical architectures and components with high cell affinity and bioactivity. Finally, we discuss how these next-generation, advanced delivery systems have been used to enhance tissue repair and regeneration and consider future implications for their use in the field of regenerative medicine.

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“…As proteins secreted by cells, growth factors act on critical functions as cell division, matrix synthesis and tissue differentiation [31,32], and play important roles in healing of bone fractures [33]. These bone growth factors include bone morphogenetic protein (BMP), vascular endothelial growth factor (VEGF), broblast growth factor (FGF), transforming growth factor-β (TGF-β) and so on.…”

Section: Ngf Accelerates Healing Of Mandible Fracturementioning

confidence: 99%

Effects of exogenous nerve growth factor on the expression of BMP-9 and VEGF in the healing of rabbit mandible fracture with local nerve injury

Yang

Cheng

Man

et al. 2020

Preprint

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Background The fracture of mandible remains one of the most facial fractures and its healing is a complex process, involving nerve and growth factors. Currently, nerve growth factor not only benefits maintenance of sympathetic neurite growth, but also takes part in intricate regulatory network to stimulate other growth factors such as bone growth protein and vascular endothelial growth factor, which promote together essential osteogenesis and angiogenesis to physiological bone formation, growth and fracture healing. Therefore, it is necessary to analysis the combination of nerve growth factor, bone growth protein-9 and vascular endothelial growth factor to accelerate healing rate of mandible fracture. Methods The models of mandible fracture with local nerve injury established in forty-eight rabbits were randomly divided into nerve growth factor group (NGF group), gelatin sponge group (GS group), blank group and intact group with 12 rabbits in each group. The fracture healing was observed with visual and X-ray after the operation, then callus tissue in mandibular fracture area were collected for HE staining observation, and quantitative RT-PCR was used to detect the expression of BMP-9 and VEGF in callus at different stages. Results The combined results of macroscopic observation, X-ray examination and histological section showed that a large number of osteoblasts and some vascular endothelial cells were found around the trabecular bone in NGF group and the amount of callus formation and reconstruction were better than GS group at 2th weeks after the operation. Quantitative RT-PCR result indicated that the expression levels of BMP-9 mRNA and VEGF mRNA in the four groups reached the highest value at the second week, and then decreased with time. At the same time, the content of BMP-9 and VEGF in callus tissue in mandibular fracture area increased significantly in NGF group than GS group. Conclusion The exogenous NGF could improve the expressions of BMP-9 and VEGF in the early stage of mandibular fracture to accelerate healing of mandible fracture. This work provides a new foundation and theoretical basis to make clear mechanism of fracture healing, thereby promoting patients’ fracture healing and reducing their disability rate.

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Collagen Implants Equipped with ’Fish Scale‘-Like Nanoreservoirs of Growth Factors for Bone Regeneration

Cited by 34 publications

References 45 publications

A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration

A living thick nanofibrous implant bifunctionalized with active growth factor and stem cells for bone regeneration

Novel biomaterial strategies for controlled growth factor delivery for biomedical applications

Effects of exogenous nerve growth factor on the expression of BMP-9 and VEGF in the healing of rabbit mandible fracture with local nerve injury

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