Analysis of the Effect of Human Type I Collagen-Derived Peptide on Bone Regenerative Capacity and Comparison with Various Collagen Materials In Vivo

<i>Background and Objectives</i>: Autologous bone grafting is the first choice for reconstructive surgery in bone defects due to trauma or malignant tumors. However, there is an increasing demand for minimally invasive alternatives involving bone regeneration using artificial materials....

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Main Authors: Tatsunori Asakura, Tran Thi Thuy Diep, Yuta Ueda, Aoi Yamada, Takahiro Tsuzuno, Naoki Takahashi, Masayuki Miyata, Koichi Tabeta, Masaki Nagata, Ken Matsuda
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Medicina
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Online Access:https://www.mdpi.com/1648-9144/61/1/57
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author Tatsunori Asakura
Tran Thi Thuy Diep
Yuta Ueda
Aoi Yamada
Takahiro Tsuzuno
Naoki Takahashi
Masayuki Miyata
Koichi Tabeta
Masaki Nagata
Ken Matsuda
author_facet Tatsunori Asakura
Tran Thi Thuy Diep
Yuta Ueda
Aoi Yamada
Takahiro Tsuzuno
Naoki Takahashi
Masayuki Miyata
Koichi Tabeta
Masaki Nagata
Ken Matsuda
author_sort Tatsunori Asakura
collection DOAJ
description <i>Background and Objectives</i>: Autologous bone grafting is the first choice for reconstructive surgery in bone defects due to trauma or malignant tumors. However, there is an increasing demand for minimally invasive alternatives involving bone regeneration using artificial materials. Biomimetic materials that replicate the body’s microscopic structure, such as Cellnest<sup>®</sup>, are gaining attention. Cellnest is a xeno-free recombinant peptide based on human type I collagen, containing a rich Arg-Gly-Asp (RGD) motif related to cell adhesion. The aim of this study was to compare the effects of Cellnest with existing collagen materials (Pelnac<sup>®</sup>, Integra<sup>®</sup>, Terudermis<sup>®</sup>) on bone regeneration and elucidate the underlying mechanisms. <i>Materials and Methods</i>: In vivo experiments involved a rat model of calvarial bone defects, in which Cellnest and other collagen materials were implanted into the defect area. Bone formation was assessed after 4 weeks using micro-computed tomography (micro-CT) and histological analysis. In vitro experiments included the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), adhesion, and migration assays, and a real-time polymerase chain reaction using rapidly expanding cells (RECs) to explore the mechanisms of Cellnest’s bone regenerative capacity. <i>Results</i>: The micro-CT analysis showed that the regenerated bone area was significantly greater in the Cellnest group (72.3%) than in the Pelnac<sup>®</sup> (25.5%), Integra<sup>®</sup> (31.6%), and Terudermis<sup>®</sup> (38.3%) groups. The histological analysis confirmed similar trends, with Cellnest showing 42.2% bone regeneration, outperforming the other materials. The in vitro assays revealed that Cellnest promoted cell proliferation, adhesion, and migration. Gene expression analysis demonstrated that Cellnest significantly increased the levels of the bone formation markers ALP and COL1. <i>Conclusions</i>: Cellnest, a human type I collagen-like peptide rich in RGD motifs, enhances bone regeneration by promoting MSC adhesion and migration, and bone formation-related gene expression. The findings suggest its potential as an effective material for bone defect reconstruction.
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spelling doaj-art-362925df450543339aebc3b7676a5e092025-01-24T13:40:24ZengMDPI AGMedicina1010-660X1648-91442025-01-016115710.3390/medicina61010057Analysis of the Effect of Human Type I Collagen-Derived Peptide on Bone Regenerative Capacity and Comparison with Various Collagen Materials In VivoTatsunori Asakura0Tran Thi Thuy Diep1Yuta Ueda2Aoi Yamada3Takahiro Tsuzuno4Naoki Takahashi5Masayuki Miyata6Koichi Tabeta7Masaki Nagata8Ken Matsuda9Department of Plastic and Reconstructive Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, JapanDivision of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, JapanDivision of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, JapanDivision of Pioneering Advanced Therapeutics, Niigata University Medical and Dental Hospital, Niigata 951-8520, JapanDivision of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, JapanDivision of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, JapanDepartment of Plastic and Reconstructive Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, JapanDivision of Periodontology, Department of Oral Biological Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, JapanDivision of Pioneering Advanced Therapeutics, Niigata University Medical and Dental Hospital, Niigata 951-8520, JapanDepartment of Plastic and Reconstructive Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan<i>Background and Objectives</i>: Autologous bone grafting is the first choice for reconstructive surgery in bone defects due to trauma or malignant tumors. However, there is an increasing demand for minimally invasive alternatives involving bone regeneration using artificial materials. Biomimetic materials that replicate the body’s microscopic structure, such as Cellnest<sup>®</sup>, are gaining attention. Cellnest is a xeno-free recombinant peptide based on human type I collagen, containing a rich Arg-Gly-Asp (RGD) motif related to cell adhesion. The aim of this study was to compare the effects of Cellnest with existing collagen materials (Pelnac<sup>®</sup>, Integra<sup>®</sup>, Terudermis<sup>®</sup>) on bone regeneration and elucidate the underlying mechanisms. <i>Materials and Methods</i>: In vivo experiments involved a rat model of calvarial bone defects, in which Cellnest and other collagen materials were implanted into the defect area. Bone formation was assessed after 4 weeks using micro-computed tomography (micro-CT) and histological analysis. In vitro experiments included the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), adhesion, and migration assays, and a real-time polymerase chain reaction using rapidly expanding cells (RECs) to explore the mechanisms of Cellnest’s bone regenerative capacity. <i>Results</i>: The micro-CT analysis showed that the regenerated bone area was significantly greater in the Cellnest group (72.3%) than in the Pelnac<sup>®</sup> (25.5%), Integra<sup>®</sup> (31.6%), and Terudermis<sup>®</sup> (38.3%) groups. The histological analysis confirmed similar trends, with Cellnest showing 42.2% bone regeneration, outperforming the other materials. The in vitro assays revealed that Cellnest promoted cell proliferation, adhesion, and migration. Gene expression analysis demonstrated that Cellnest significantly increased the levels of the bone formation markers ALP and COL1. <i>Conclusions</i>: Cellnest, a human type I collagen-like peptide rich in RGD motifs, enhances bone regeneration by promoting MSC adhesion and migration, and bone formation-related gene expression. The findings suggest its potential as an effective material for bone defect reconstruction.https://www.mdpi.com/1648-9144/61/1/57type I collagenbone regenerationRGD motifsrecombinant peptidesscaffolding materialmesenchymal stem cell (MSC)
spellingShingle Tatsunori Asakura
Tran Thi Thuy Diep
Yuta Ueda
Aoi Yamada
Takahiro Tsuzuno
Naoki Takahashi
Masayuki Miyata
Koichi Tabeta
Masaki Nagata
Ken Matsuda
Analysis of the Effect of Human Type I Collagen-Derived Peptide on Bone Regenerative Capacity and Comparison with Various Collagen Materials In Vivo
Medicina
type I collagen
bone regeneration
RGD motifs
recombinant peptides
scaffolding material
mesenchymal stem cell (MSC)
title Analysis of the Effect of Human Type I Collagen-Derived Peptide on Bone Regenerative Capacity and Comparison with Various Collagen Materials In Vivo
title_full Analysis of the Effect of Human Type I Collagen-Derived Peptide on Bone Regenerative Capacity and Comparison with Various Collagen Materials In Vivo
title_fullStr Analysis of the Effect of Human Type I Collagen-Derived Peptide on Bone Regenerative Capacity and Comparison with Various Collagen Materials In Vivo
title_full_unstemmed Analysis of the Effect of Human Type I Collagen-Derived Peptide on Bone Regenerative Capacity and Comparison with Various Collagen Materials In Vivo
title_short Analysis of the Effect of Human Type I Collagen-Derived Peptide on Bone Regenerative Capacity and Comparison with Various Collagen Materials In Vivo
title_sort analysis of the effect of human type i collagen derived peptide on bone regenerative capacity and comparison with various collagen materials in vivo
topic type I collagen
bone regeneration
RGD motifs
recombinant peptides
scaffolding material
mesenchymal stem cell (MSC)
url https://www.mdpi.com/1648-9144/61/1/57
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