Design and Use of Chimeric Proteins Containing a Collagen-Binding Domain for Wound Healing and Bone Regeneration

Addi, Cyril; Murschel, Frédéric; G, de Crescenzo

doi:10.1089/ten.teb.2016.0280

Cited by 37 publications

(41 citation statements)

References 196 publications

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“…Further, taking cue from a recent review, we plan to design collagen binding osteoinductive peptides for wound healing and bone tissue regeneration. [42] Taken together, the 3D hybrid nanofiber aerogels incorporated with osteoinductive peptides is a promising direction for the development of synthetic bone grafts. Another approach for promoting bone tissue ingrowth into the defect area is through the fabrication of porous scaffolds with radially aligned pores by directional freezing.…”

Section: Discussionmentioning

confidence: 99%

Novel 3D Hybrid Nanofiber Aerogels Coupled with BMP‐2 Peptides for Cranial Bone Regeneration

Weng

Boda

Wang

et al. 2018

Adv Healthcare Materials

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An ideal synthetic bone graft is a combination of the porous and nanofibrous structure presented by natural bone tissue as well as osteoinductive biochemical factors such as bone morphogenetic protein 2 (BMP-2). In this work, ultralight 3D hybrid nanofiber aerogels composed of electrospun PLGA-collagen-gelatin and Sr-Cu codoped bioactive glass fibers with incorporation of heptaglutamate E7 domain specific BMP-2 peptides have been developed and evaluated for their potential in cranial bone defect healing. The nanofiber aerogels are surgically implanted into 8 mm × 1 mm (diameter × thickness) critical-sized defects created in rat calvariae. A sustained release of E7-BMP-2 peptide from the degradable hybrid aerogels significantly enhances bone healing and defect closure over 8 weeks in comparison to unfilled defects. Histomorphometry and X-ray microcomputed tomography (µ-CT) analysis reveal greater bone volume and bone formation area in case of the E7-BMP-2 peptide loaded hybrid nanofiber aerogels. Further, histopathology data divulged a near complete nanofiber aerogel degradation along with enhanced vascularization of the regenerated tissue. Together, this study for the first time demonstrates the fabrication of 3D hybrid nanofiber aerogels from 2D electrospun fibers and their loading with therapeutic osteoinductive BMP-2 mimicking peptide for cranial bone tissue regeneration.

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Section: Discussionmentioning

confidence: 99%

Novel 3D Hybrid Nanofiber Aerogels Coupled with BMP‐2 Peptides for Cranial Bone Regeneration

Weng

Boda

Wang

et al. 2018

Adv Healthcare Materials

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“…When a blood vessel is injured, collagen beneath the endothelial cells is exposed to proteins in the blood, and VWF binding to collagen initiates the thrombosis cascade (26). The VWF A domain has the highest affinity for collagen among reported non-bacterial origin proteins/peptides (27). Particularly within the A domain, the A3 domain of VWF has been reported as a collagen-binding domain (CBD, using this abbreviation to refer specifically to the VWF A3 collagen-binding domain) (28).…”

Section: Introductionmentioning

confidence: 99%

Targeted antibody and cytokine cancer immunotherapies through collagen affinity

et al. 2019

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Cancer immunotherapy with immune checkpoint inhibitors (CPI) and interleukin (IL)-2 has demonstrated clinical efficacy but is frequently accompanied with severe adverse events caused by excessive and systemic immune system activation. Here, we addressed this need by targeting both the CPI antibodies anti-cytotoxic T-lymphocyte antigen 4 antibody (αCTLA4) + anti-programmed death-ligand 1 antibody (αPD-L1) and the cytokine IL-2 to tumors via conjugation (for the antibodies) or recombinant fusion (for the cytokine) to a collagen-binding domain (CBD) derived from the blood protein von Willebrand factor (VWF) A3 domain, harnessing the exposure of tumor stroma collagen to blood components due to the leakiness of the tumor vasculature. We show that intravenously (i.v.) administered CBD protein accumulated mainly in tumors. CBD conjugation or fusion decreases the systemic toxicity of both αCTLA4+αPD-L1 combination therapy and IL-2, for example eliminating hepatotoxicity with the CPI molecules and ameliorating pulmonary edema with IL-2. Both CBD-CPI and CBD-IL-2 suppressed tumor growth compared to their unmodified forms in multiple murine cancer models, and both CBD-CPI and CBD-IL-2 increased tumor-infiltrating CD8+ T cells. In an orthotopic breast tumor model, combination treatment with CPI and IL-2 eradicated tumors in 9 of 13 animals with the CBD-modified drugs, whereas it did so in only 1 of 13 animals with the unmodified drugs. Thus, the A3 domain of VWF can be used to improve safety and efficacy of systemically-administered tumor drugs with high translational promise.

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“…We then further detected the expression of BDNF in TBI lesions and found that the expression of BDNF in TBI lesions was higher in TBI + CBD‐BDNF group than that in TBI group and TBI + BDNF group. Actually, collagen‐derived biomaterials have been widely developed for tissue engineering and regenerative medicine purposes for their excellent biocompatibility and biodegradability, along with high safety and weak antigenicity . Therefore, we suppose that the superior effects of CBD‐BDNF come from its better ability to cross the blood–brain barrier, which makes it promising in clinical application.…”

Section: Discussionmentioning

confidence: 99%

Brain-derived neurotrophic factor fused with a collagen-binding domain inhibits neuroinflammation and promotes neurological recovery of traumatic brain injury mice via TrkB signalling

Yin

Zhao

Qiu

2020

Journal of Pharmacy and Pharmacology

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Objectives As one of the vital nutrient factors in central nervous system (CNS), brain‐derived neurotrophic factor (BDNF) can significantly attenuate neuron damage and promote neurogenesis. Nevertheless, little research has been conducted on regulating the effect of BDNF on the inflammatory response after traumatic brain injury (TBI). Methods In this study, we used BDNF fused with a collagen‐binding domain (CBD‐BDNF) to maintain a sufficient concentration of BDNF in the TBI hemisphere, and then, the regulatory effects of BDNF and CBD‐BDNF on the inflammatory response of microglia were investigated both on a TBI mice model in vivo and LPS‐stimulated microglia experiment in vitro. Key findings The results revealed that BDNF and CBD‐BDNF had similar effects on attenuating the pro‐inflammatory reactions but promoting anti‐inflammatory responses of microglia induced by LPS in vitro. Furthermore, CBD‐BDNF significantly improved the neurological behaviours of TBI mice and alleviated the inflammatory reaction after TBI, while BDNF had weaker effects compared with those of CBD‐BDNF. Additionally, the TrkB inhibitor K252a significantly inhibited the above effects of CBD‐BDNF. Conclusions In conclusion, CBD‐BDNF can promote the anti‐inflammatory function of microglia and neurological recovery of TBI mice through TrkB signalling.

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Design and Use of Chimeric Proteins Containing a Collagen-Binding Domain for Wound Healing and Bone Regeneration

Cited by 37 publications

References 196 publications

Novel 3D Hybrid Nanofiber Aerogels Coupled with BMP‐2 Peptides for Cranial Bone Regeneration

Novel 3D Hybrid Nanofiber Aerogels Coupled with BMP‐2 Peptides for Cranial Bone Regeneration

Targeted antibody and cytokine cancer immunotherapies through collagen affinity

Brain-derived neurotrophic factor fused with a collagen-binding domain inhibits neuroinflammation and promotes neurological recovery of traumatic brain injury mice via TrkB signalling

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