A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering

Despite its intrinsic ability to regenerate form and function after injury, bone tissue can be challenged by a multitude of pathological conditions. While innovative approaches have helped to unravel the cascades of bone healing, this knowledge has so far not improved the clinical outcomes of bone defect treatment. Recent findings have allowed us to gain in-depth knowledge about the physiological conditions and biological principles of bone regeneration. Now it is time to transfer the lessons learned from bone healing to the challenging scenarios in defects and employ innovative technologies to enable biomaterial-based strategies for bone defect healing. This review aims to provide an overview on endogenous cascades of bone material formation and how these are transferred to new perspectives in biomaterial-driven approaches in bone regeneration. Cite this article: T. Winkler, F. A. Sass, G. N. Duda, K. Schmidt-Bleek. A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: The unsolved challenge. Bone Joint Res 2018;7:232–243. DOI: 10.1302/2046-3758.73.BJR-2017-0270.R1.

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Application of graphene oxide-based hydrogels in bone tissue engineering

Current Stem Cell Research & Therapy ◽

10.2174/1574888x16666210719170042 ◽

2021 ◽

Vol 16 ◽

Author(s):

Kuang Zhihui ◽

Ni Licheng ◽

Xu Jianxiang ◽

Xiao Shining ◽

Zhou Chenwei ◽

...

Keyword(s):

Tissue Engineering ◽

Graphene Oxide ◽

Mechanical Strength ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Bone Defect ◽

High Performance ◽

Essential Role ◽

Defect Healing ◽

Bone Defect Healing

: This paper provides a review on the applications of some graphene oxide-based hydrogels in bone tissue engineering. Hydrogels used in bone tissue engineering usually require suitable biocompatibility, porosity, and mechanical strength. By adding GO, under the original hydrogel condition, the various indexes of the composite hydrogel can reach more suitable conditions for inducing bone defect healing. This article also introduces some high-performance graphene oxide-based hydrogels, which are likely to play an essential role in bone tissue engineering in the future.

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3D-Bioprinting Strategies Based on In Situ Bone-Healing Mechanism for Vascularized Bone Tissue Engineering

Micromachines ◽

10.3390/mi12030287 ◽

2021 ◽

Vol 12 (3) ◽

pp. 287

Author(s):

Ye Lin Park ◽

Kiwon Park ◽

Jae Min Cha

Keyword(s):

Tissue Engineering ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Bone Healing ◽

Critical Size ◽

Current Knowledge ◽

3D Bioprinting ◽

The Past ◽

Regeneration Processes

Over the past decades, a number of bone tissue engineering (BTE) approaches have been developed to address substantial challenges in the management of critical size bone defects. Although the majority of BTE strategies developed in the laboratory have been limited due to lack of clinical relevance in translation, primary prerequisites for the construction of vascularized functional bone grafts have gained confidence owing to the accumulated knowledge of the osteogenic, osteoinductive, and osteoconductive properties of mesenchymal stem cells and bone-relevant biomaterials that reflect bone-healing mechanisms. In this review, we summarize the current knowledge of bone-healing mechanisms focusing on the details that should be embodied in the development of vascularized BTE, and discuss promising strategies based on 3D-bioprinting technologies that efficiently coalesce the abovementioned main features in bone-healing systems, which comprehensively interact during the bone regeneration processes.

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Comparative Study on the Effect of the Different Harvesting Sources of Demineralized Bone Particles on the Bone Regeneration of a Composite Gellan Gum Scaffold for Bone Tissue Engineering Applications

ACS Applied Bio Materials ◽

10.1021/acsabm.0c01549 ◽

2021 ◽

Vol 4 (2) ◽

pp. 1900-1911

Author(s):

Hun Hwi Cho ◽

Su Young Been ◽

Woo Youp Kim ◽

Jeong Min Choi ◽

Joo Hee Choi ◽

...

Keyword(s):

Tissue Engineering ◽

Comparative Study ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Bone Tissue ◽

Gellan Gum ◽

Engineering Applications ◽

Bone Particles ◽

Demineralized Bone

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Osteon-mimetic 3D nanofibrous scaffold enhancing stem cell proliferation and osteogenic differentiation for bone regeneration

Biomaterials Science ◽

10.1039/d1bm01489g ◽

2022 ◽

Author(s):

Ting Song ◽

Jianhua Zhou ◽

Ming Shi ◽

Liuyang Xuan ◽

Huamin Jiang ◽

...

Keyword(s):

Tissue Engineering ◽

Cell Proliferation ◽

Stem Cell ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Osteogenic Differentiation ◽

Bone Tissue ◽

Nanofibrous Scaffold ◽

Hierarchical Microstructure ◽

Stem Cell Proliferation

Scaffold microstructure is important for bone tissue engineering. Failure to synergistically imitate the hierarchical microstructure of bone component, such as osteon with concentric multilayers assembled by nanofibers, hindered the performance...

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Chitosan/β-TCP composites scaffolds coated with silk fibroin: a bone tissue engineering approach

Biomedical Materials ◽

10.1088/1748-605x/ac355a ◽

2021 ◽

Vol 17 (1) ◽

pp. 015003

Author(s):

Lya Piaia ◽

Simone S Silva ◽

Joana M Gomes ◽

Albina R Franco ◽

Emanuel M Fernandes ◽

...

Keyword(s):

Tissue Engineering ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Bone Tissue ◽

Silk Fibroin ◽

Cellular Proliferation ◽

Mechanical Performance ◽

Tissue Growth ◽

Polymeric Scaffolds ◽

Bioactive Agents

Abstract Bone regeneration and natural repair are long-standing processes that can lead to uneven new tissue growth. By introducing scaffolds that can be autografts and/or allografts, tissue engineering provides new approaches to manage the major burdens involved in this process. Polymeric scaffolds allow the incorporation of bioactive agents that improve their biological and mechanical performance, making them suitable materials for bone regeneration solutions. The present work aimed to create chitosan/beta-tricalcium phosphate-based scaffolds coated with silk fibroin and evaluate their potential for bone tissue engineering. Results showed that the obtained scaffolds have porosities up to 86%, interconnectivity up to 96%, pore sizes in the range of 60–170 μm, and a stiffness ranging from 1 to 2 MPa. Furthermore, when cultured with MC3T3 cells, the scaffolds were able to form apatite crystals after 21 d; and they were able to support cell growth and proliferation up to 14 d of culture. Besides, cellular proliferation was higher on the scaffolds coated with silk. These outcomes further demonstrate that the developed structures are suitable candidates to enhance bone tissue engineering.

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Mineralized Nanofibers for Bone Tissue Engineering

Biomedical Engineering ◽

10.4018/978-1-5225-3158-6.ch020 ◽

2018 ◽

pp. 461-475 ◽

Cited By ~ 1

Author(s):

Ozan Karaman

Keyword(s):

Tissue Engineering ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Bone Tissue ◽

Three Dimensional ◽

Bone Grafts ◽

Tissue Engineering Scaffolds ◽

Promising Alternative ◽

Biomimetic Scaffolds

The limitation of orthopedic fractures and large bone defects treatments has brought the focus on fabricating bone grafts that could enhance ostegenesis and vascularization in-vitro. Developing biomimetic materials such as mineralized nanofibers that can provide three-dimensional templates of the natural bone extracellular-matrix is one of the most promising alternative for bone regeneration. Understanding the interactions between the structure of the scaffolds and cells and therefore the control cellular pathways are critical for developing functional bone grafts. In order to enhance bone regeneration, the engineered scaffold needs to mimic the characteristics of composite bone ECM. This chapter reviews the fabrication of and fabrication techniques for fabricating biomimetic bone tissue engineering scaffolds. In addition, the chapter covers design criteria for developing the scaffolds and examples of enhanced osteogenic differentiation outcomes by fabricating biomimetic scaffolds.

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Enhanced Cell Proliferation and Osteogenesis Differentiation through a Combined Treatment of Poly-L-Lysine-Coated PLGA/Graphene Oxide Hybrid Fiber Matrices and Electrical Stimulation

Journal of Nanomaterials ◽

10.1155/2020/5892506 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15

Author(s):

Jiaqi Zhu ◽

Zhiping Qi ◽

Changjun Zheng ◽

Pan Xue ◽

Chuan Fu ◽

...

Keyword(s):

Tissue Engineering ◽

Cell Proliferation ◽

Graphene Oxide ◽

Electrical Stimulation ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Bone Tissue ◽

Cellular Response ◽

Hybrid Fiber ◽

Fiber Matrices

Bone tissue engineering scaffold provides an effective treatment for bone defect repair. Biodegradable bone scaffold made of various synthetic and natural materials can be used as bone substitutes and grafts for defect site, which has great potential to support bone regeneration. Regulation of cell-scaffold material interactions is an important factor for modulating the cellular activity in bone tissue engineering scaffold applications. Thus, the hydrophilic, mechanical, and chemical properties of scaffold materials directly affect the results of bone regeneration and functional recovery. In this study, a poly-L-lysine (PLL) surface-modified poly(lactic-co-glycolic acid) (PLGA)/graphene oxide (GO) (PLL-PLGA/GO) hybrid fiber matrix was fabricated for bone tissue regeneration. Characterization of the resultant hybrid fiber matrices was done using scanning electron microscopy (SEM), contact angle, and a material testing machine. According to the results obtained from the test above, the PLL-PLGA/GO hybrid fiber matrices exhibited high wettability and mechanical strength. The special surface characteristics of PLL-PLGA/GO hybrid fiber matrices were more beneficial for protein adsorption and inhibit the proliferation of pathogens. Moreover, the enhanced regulation of MC3T3-E1 cell proliferation and differentiation was observed, when the resultant hybrid fiber matrices were combined with electrical stimulation (ES). The cellular response of MC3T3-E1 cells including cell adhesion, proliferation, alkaline phosphatase (ALP) activity, calcium deposition, and osteogenesis-related gene expression was significantly enhanced with the synergistic effect of resultant hybrid fiber matrices and ES. These data indicate that the PLL-PLGA/GO hybrid fiber matrices supported the cellular response in terms of cell proliferation and osteogenesis differentiation in the presence of electrical stimulation, which could be a potential treatment for bone defect.

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Collagen Scaffolds Containing Hydroxyapatite-CaO Fiber Fragments for Bone Tissue Engineering

Polymers ◽

10.3390/polym12051174 ◽

2020 ◽

Vol 12 (5) ◽

pp. 1174 ◽

Cited By ~ 1

Author(s):

Shiao-Wen Tsai ◽

Sheng-Siang Huang ◽

Wen-Xin Yu ◽

Yu-Wei Hsu ◽

Fu-Yin Hsu

Keyword(s):

Tissue Engineering ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Bone Tissue ◽

Drug Loading ◽

Sol Gel ◽

Regeneration Ability ◽

Burst Release ◽

Electrospinning Technique

Collagen (COL) and hydroxyapatite (HAp) are the major components of bone, therefore, COL-HAp composites have been widely used as bone substitutes to promote bone regeneration. We have reported that HAp-CaO fibers (HANFs), which were fabricated by a sol-gel route followed by an electrospinning technique, possessed good drug-loading efficiency and limited the burst release of tetracycline. In the present study, we used HANF fragments to evaluate the effects of COL-HANF scaffolds on MG63 osteoblast-like cell behaviors. COL-HANF composite scaffolds in which the average diameter of HANFs was approximately 461 ± 186 nm were fabricated by a freeze-drying process. The alkaline phosphatase activity and the protein expression levels of OCN and BSP showed that compared with COL alone, the COL-HANF scaffold promoted the differentiation of MG63 osteoblast-like cells. In addition, the bone regeneration ability of the COL-HANF scaffold was examined by using a rabbit condylar defect model in vivo. The COL-HANF scaffold was biodegradable and promoted bone regeneration eight weeks after the operation. Hence, we concluded that the COL-HANF scaffold has potential as a bone graft for bone tissue engineering.

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