Controlled release of basic fibroblast growth factor from a peptide biomaterial for bone regeneration

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Abstract

Self-assembled peptide scaffolds based on D-RADA16 are an important matrix for controlled drug release and three-dimensional cell culture. In this work, D-RADA16 peptide hydrogels were coated on artificial bone composed of nano-hydroxyapatite/polyamide 66 (nHA/PA66) to obtain a porous drug-releasing structure for treating bone defects. The developed materials were characterized via transmission electron microscopy and scanning electron microscopy. The proliferation and adhesion of bone mesenchymal stem cells (BMSCs) were examined by confocal laser microscopy and CCK-8 experiments. The osteogenic ability of the porous materials towards bone BMSCs was examined in vitro by staining with Alizarin Red S and alkaline phosphatase, and bioactivity was evaluated in vivo. The results revealed that nHA/PA66/D-RADA16/bFGF reduces the degradation rate of D-RADA16 hydrogels and prolongs sustained release of bFGF, which would promote BMSCs proliferation, adhesion and osteogenesis in vitro and bone repair in vivo. Thus, it deserves more attention and is worthy of further research.

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TGF-β and BMP Signaling in Osteoblast Differentiation and Bone Formation

Guiqian Chen, Chuxia Deng, YI-PING LI (2012)

Transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP) signaling is involved in a vast majority of cellular processes and is fundamentally important throughout life. TGF-β/BMPs have widely recognized roles in bone formation during mammalian development and exhibit versatile regulatory functions in the body. Signaling transduction by TGF-β/BMPs is specifically through both canonical Smad-dependent pathways (TGF-β/BMP ligands, receptors and Smads) and non-canonical Smad-independent signaling pathway (e.g. p38 mitogen-activated protein kinase pathway, MAPK). Following TGF-β/BMP induction, both the Smad and p38 MAPK pathways converge at the Runx2 gene to control mesenchymal precursor cell differentiation. The coordinated activity of Runx2 and TGF-β/BMP-activated Smads is critical for formation of the skeleton. Recent advances in molecular and genetic studies using gene targeting in mice enable a better understanding of TGF-β/BMP signaling in bone and in the signaling networks underlying osteoblast differentiation and bone formation. This review summarizes the recent advances in our understanding of TGF-β/BMP signaling in bone from studies of genetic mouse models and human diseases caused by the disruption of TGF-β/BMP signaling. This review also highlights the different modes of cross-talk between TGF-β/BMP signaling and the signaling pathways of MAPK, Wnt, Hedgehog, Notch, and FGF in osteoblast differentiation and bone formation.

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Bone regeneration: current concepts and future directions

Rozalia Dimitriou, Elena Jones, Dennis McGonagle … (2011)

Bone regeneration is a complex, well-orchestrated physiological process of bone formation, which can be seen during normal fracture healing, and is involved in continuous remodelling throughout adult life. However, there are complex clinical conditions in which bone regeneration is required in large quantity, such as for skeletal reconstruction of large bone defects created by trauma, infection, tumour resection and skeletal abnormalities, or cases in which the regenerative process is compromised, including avascular necrosis, atrophic non-unions and osteoporosis. Currently, there is a plethora of different strategies to augment the impaired or 'insufficient' bone-regeneration process, including the 'gold standard' autologous bone graft, free fibula vascularised graft, allograft implantation, and use of growth factors, osteoconductive scaffolds, osteoprogenitor cells and distraction osteogenesis. Improved 'local' strategies in terms of tissue engineering and gene therapy, or even 'systemic' enhancement of bone repair, are under intense investigation, in an effort to overcome the limitations of the current methods, to produce bone-graft substitutes with biomechanical properties that are as identical to normal bone as possible, to accelerate the overall regeneration process, or even to address systemic conditions, such as skeletal disorders and osteoporosis.

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Bone substitutes: a review of their characteristics, clinical use, and perspectives for large bone defects management

Gabriel Fernandez de Grado, Laetitia Keller, Ysia Idoux-Gillet … (2018)

Bone replacement might have been practiced for centuries with various materials of natural origin, but had rarely met success until the late 19th century. Nowadays, many different bone substitutes can be used. They can be either derived from biological products such as demineralized bone matrix, platelet-rich plasma, hydroxyapatite, adjunction of growth factors (like bone morphogenetic protein) or synthetic such as calcium sulfate, tri-calcium phosphate ceramics, bioactive glasses, or polymer-based substitutes. All these substitutes are not suitable for every clinical use, and they have to be chosen selectively depending on their purpose. Thus, this review aims to highlight the principal characteristics of the most commonly used bone substitutes and to give some directions concerning their clinical use, as spine fusion, open-wedge tibial osteotomy, long bone fracture, oral and maxillofacial surgery, or periodontal treatments. However, the main limitations to bone substitutes use remain the management of large defects and the lack of vascularization in their central part, which is likely to appear following their utilization. In the field of bone tissue engineering, developing porous synthetic substitutes able to support a faster and a wider vascularization within their structure seems to be a promising way of research.

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Journal

Journal ID (nlm-ta): R Soc Open Sci

Journal ID (iso-abbrev): R Soc Open Sci

Journal ID (publisher-id): RSOS

Journal ID (hwp): royopensci

Title: Royal Society Open Science

Publisher: The Royal Society

ISSN (Electronic): 2054-5703

Publication date Collection: April 2020

Publication date (Electronic): 1 April 2020

Publication date PMC-release: 1 April 2020

Volume: 7

Issue: 4

Electronic Location Identifier: 191830

Affiliations

[1 ]Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University , No. 1 Youyi Road, Chongqing, Yuzhong District 400016, People's Republic of China

[2 ]Department of Orthopaedics, Third Affiliated Hospital of Chongqing Medical University , No. 1 Shuanghu Road, Chongqing City, Yubei District 401120, People's Republic of China

[3 ]Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College , No. 63 Wenhua Road, Nanchong City, Sichuan Province 637000, People's Republic of China

[4 ]Department of Orthopaedics, Hospital (T.C.M) Affiliated to Southwest Medical University , No. 182 Chunhui Road, Luzhou City, Sichuan Province, 646000, People's Republic of China

Author notes

Author for correspondence: Bo Qiao e-mail: qiaobo1985@ 123456163.com

Author for correspondence: Dianming Jiang e-mail: jdm571026@ 123456vip.163.com

[†]

These authors contributed equally to this work.

Electronic supplementary material is available online at https://doi.org/10.6084/m9.figshare.c.4902408.

Author information

WeiKang Zhao http://orcid.org/0000-0002-5594-213X

Article

Publisher ID: rsos191830

DOI: 10.1098/rsos.191830

PMC ID: 7211882

PubMed ID: 32431879

SO-VID: d18ef901-0f93-466b-8e19-1a578bbfd8ae

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Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.

History

Date received : 17 October 2019

Date accepted : 12 February 2020

Funding

Funded by: National Natural Science Foundation of China;

Award ID: (81472057)

Funded by: The Applied Basic Research Programs of Science and Technology Department of Sichuan Province.;

Award ID: (2018JY0250)

Funded by: Natural Science Foundation of Chongqing province;

Award ID: (KJZH17110)

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cover-date April, 2020

Keywords: bfgf,sustained release,self-assembling peptide,porous nha/pa66,bone mesenchymal stem cells

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Keywords: bfgf, sustained release, self-assembling peptide, porous nha/pa66, bone mesenchymal stem cells

Controlled release of basic fibroblast growth factor from a peptide biomaterial for bone regeneration

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Most cited references 42

TGF-β and BMP Signaling in Osteoblast Differentiation and Bone Formation

Bone regeneration: current concepts and future directions

Bone substitutes: a review of their characteristics, clinical use, and perspectives for large bone defects management

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