Screening of Osteogenic-Enhancing Short Peptides from BMPs for Biomimetic Material Applications

Kanie, Kei; Kurimoto, Rio; Tian, Jing; Ebisawa, Katsumi; Honda, Hiroyuki; Kato, Ryuji

doi:10.3390/ma9090730

Cited by 18 publications

(16 citation statements)

References 44 publications

(60 reference statements)

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“…[9] Alternatively, short chain BMP-2 peptides have been developed to mimic the activity of BMP-2 proteins by binding to their cell receptors. [10] In contrast to soluble growth factors, calcium-coupling BMP-2 peptides (KIPKASSVPTELSAISTLYL) have been bound to scaffolds to facilitate bone regeneration. [11] Studies also showed that modified peptides derived from BMP-2 with a heptaglutamate domain (E7) significantly improved their binding to the hydroxyapatite surface through Ca coupling.…”

Section: Introductionmentioning

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: Introductionmentioning

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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“…Many studies have attempted to mediate cell behaviors by modifying the surfaces of the biomaterials. 7–13,16 While bioactivity of individual short peptides used in the present study has previously be reported, 17–20 surface modification of PBSu/TCP composites by dual immobilization of these short peptides has not yet been reported. The present study has shown, for the first time, that sequential immobilization of COLsp and BMP-2sp was successfully achieved, with each of the peptides being chemically bound to the HPBSu/TCP surface and the resulting surface remaining bioactive.…”

Section: Discussionmentioning

confidence: 63%

“…11,16 In addition to COLsp, a short peptide derived from its corresponding full-length bone morphogenetic protein 2 (BMP-2), designated here as BMP-2sp, has been reported to possess an osteogenic activity both in vitro and in vivo. 17–20 While intracellular signallings transmitted by osteogenic molecules control osteoblast differentiation and mineralization, reciprocal regulation of Col-I and BMP-2 has been shown to significantly influence cell proliferation and osteoblast differentiation and function. 21–23…”

Section: Introductionmentioning

confidence: 99%

Analysis of sequential dual immobilization of type I collagen and BMP-2 short peptides on hydrolyzed poly(buthylene succinate)/β-tricalcium phosphate composites for bone tissue engineering

et al. 2019

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Although attempts have been made to immobilize dual short peptides on a biomaterial surface, the optimization, characterization and functional analysis of the peptide immobilization onto poly(buthylene succinate)/β-tricalcium phosphate (PBSu/TCP) composites have not yet been reported. The present study was, therefore, carried out to optimize and characterize the dual immobilization of type I collagen short peptide (COLsp) and bone morphogenetic protein-2 short peptide (BMP-2sp) onto hydrolyzed PBSu/TCP (HPBSu/TCP) composites, and the bioactivity of the resulting dual peptide-immobilized surfaces was also determined in vitro. The results demonstrated that sequential immobilization of the dual short peptides was successfully established. Each of the peptides was chemically bound to the 1.5 M NaOH-treated composite (with the PBSu to TCP weight ratio of 60:40) (HPBSu/TCP-6040–1.5); bright red fluorescence of COLsp (25 µM) and vividly green fluorescence of BMP-2sp (50 µM) were individually observed explicitly on the dual peptide-immobilized material. As a result, the HPBSu/TCP-6040–1.5 composite film conjugated with both 25 µM Col I and 50 µM BMP-2 was examined for its osteogenic efficacy. The results showed that COLsp/BMP-2sp-immobilized HPBSu/TCP composite significantly enhanced hMSC proliferation as well as osteoblast differentiation of hMSCs under osteogenic induction. Most importantly, COLsp/BMP-2sp-immobilized HPBSu/TCP composite induced biomineralization in the absence of any additional osteogenic stimulus. The present study has successfully demonstrated the sequential immobilization of the dual short peptides, i.e., COLsp and BMP-2sp, on HPBSu/TCP surface, with each short peptide being chemically bound to the hydrolyzed composite surface. The COLsp/BMP-2sp-immobilized HPBSu/TCP film possessed the bioactivities of the respective full-length proteins by stimulating hMSC proliferation, osteoblast differentiation and, most importantly, mineralization without the requirement of exogenous osteogenic supplements. This suggests highly improved performance of the biologically responsive HPBSu/TCP composite and thus its potential use in bone tissue engineering.

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“…In 2016, Kanie et al 501 combined peptide microarrays with in silico screening to define candidate peptides that could induce osteogenic-selective proliferation and differentiation of human MSCs. The sequences of 19 types of natural BMPs (known to be bone regenerative molecules) were obtained from UniProt, and aligned with a peptide database (graphical image of the alignment, Figure 24 A).…”

Section: Microarray Strategies Applied In Biomaterials Screening and Used To Model The Cellular Microenvironmentmentioning

confidence: 99%

High-Throughput Methods in the Discovery and Study of Biomaterials and Materiobiology

et al. 2021

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The complex interaction of cells with biomaterials (i.e., materiobiology) plays an increasingly pivotal role in the development of novel implants, biomedical devices, and tissue engineering scaffolds to treat diseases, aid in the restoration of bodily functions, construct healthy tissues, or regenerate diseased ones. However, the conventional approaches are incapable of screening the huge amount of potential material parameter combinations to identify the optimal cell responses and involve a combination of serendipity and many series of trial-and-error experiments. For advanced tissue engineering and regenerative medicine, highly efficient and complex bioanalysis platforms are expected to explore the complex interaction of cells with biomaterials using combinatorial approaches that offer desired complex microenvironments during healing, development, and homeostasis. In this review, we first introduce materiobiology and its high-throughput screening (HTS). Then we present an in-depth of the recent progress of 2D/3D HTS platforms (i.e., gradient and microarray) in the principle, preparation, screening for materiobiology, and combination with other advanced technologies. The Compendium for Biomaterial Transcriptomics and high content imaging, computational simulations, and their translation toward commercial and clinical uses are highlighted. In the final section, current challenges and future perspectives are discussed. High-throughput experimentation within the field of materiobiology enables the elucidation of the relationships between biomaterial properties and biological behavior and thereby serves as a potential tool for accelerating the development of high-performance biomaterials.

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Screening of Osteogenic-Enhancing Short Peptides from BMPs for Biomimetic Material Applications

Cited by 18 publications

References 44 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

Analysis of sequential dual immobilization of type I collagen and BMP-2 short peptides on hydrolyzed poly(buthylene succinate)/β-tricalcium phosphate composites for bone tissue engineering

High-Throughput Methods in the Discovery and Study of Biomaterials and Materiobiology

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