scholarly journals Biophysical Stimuli as the Fourth Pillar of Bone Tissue Engineering

Author(s):  
Zhuowen Hao ◽  
Zhenhua Xu ◽  
Xuan Wang ◽  
Yi Wang ◽  
Hanke Li ◽  
...  

The repair of critical bone defects remains challenging worldwide. Three canonical pillars (biomaterial scaffolds, bioactive molecules, and stem cells) of bone tissue engineering have been widely used for bone regeneration in separate or combined strategies, but the delivery of bioactive molecules has several obvious drawbacks. Biophysical stimuli have great potential to become the fourth pillar of bone tissue engineering, which can be categorized into three groups depending on their physical properties: internal structural stimuli, external mechanical stimuli, and electromagnetic stimuli. In this review, distinctive biophysical stimuli coupled with their osteoinductive windows or parameters are initially presented to induce the osteogenesis of mesenchymal stem cells (MSCs). Then, osteoinductive mechanisms of biophysical transduction (a combination of mechanotransduction and electrocoupling) are reviewed to direct the osteogenic differentiation of MSCs. These mechanisms include biophysical sensing, transmission, and regulation. Furthermore, distinctive application strategies of biophysical stimuli are presented for bone tissue engineering, including predesigned biomaterials, tissue-engineered bone grafts, and postoperative biophysical stimuli loading strategies. Finally, ongoing challenges and future perspectives are discussed.

Author(s):  
I. A Stamboliev ◽  
Julia Vladimirovna Gazhva ◽  
S. G Ivashkevich ◽  
V. M Ryabova

This article discusses the modern approaches of bone tissue engineering in oral and maxillofacial surgery for repair of bone integrity. Describes the new biomaterials in bone tissue engineering, complex scaffolds containing MSC for bone repair of large and critical bone defects, the criteria for selecting biomaterial scaffolds, as well as their positive and negative properties.


2021 ◽  
Author(s):  
Xiang Zhang ◽  
Jialei Chen ◽  
Hongren Wang ◽  
Xin Duan ◽  
Feng Gao

Abstract BACKGROUND: Bone defects still pose various challenges in osteology. As one of the treatment options for bone defects, bone tissue engineering requires biomaterials with good biocompatibility and seed cells with good differentiation capacity. This study aimed to fabricate a 3D-printed polylactic acid and hydroxyapatite (PLA/HA) composite scaffold with urine-derived stem cells (USCs) to study its therapeutic effect in a model of skull defect in rats.METHODS: USCs, isolated and extracted from the urine of healthy adult males, were inoculated onto a 3D-printed PLA/HA composite scaffold and a PLA scaffold. Skull defect model rats were randomly divided into three groups (control, PLA, and PLA/HA). Twelve weeks after implanting scaffolds containing USCs into rats with a skull defect, the therapeutic efficacy was evaluated by real-time PCR, micro-CT, histology, and immunohistochemistry.RESULTS: The 3D-printed PLA/HA composite scaffold had good mechanical properties and porosity. The adhesion and proliferation of USCs on scaffolds also demonstrated excellent biocompatibility. PLA and PLA/HA containing USCs promoted bone regeneration in the defect area, supported by the general observation and CT images at 12 weeks after treatment, with coverage of 74.6%±1.9% and 96.7%±1.6%, respectively. Immunohistochemical staining showed a progressive process of new bone formation on PLA/HA scaffolds containing USCs at the defect site compared to that in PLA and control groups.CONCLUSION: The 3D-printed PLA/HA composite scaffold with USCs was successfully applied to the skull defect in rats. Under the linkage of the scaffold, the proliferation, differentiation, and osteogenesis expression of USCs were promoted near the bone defect area. These findings demonstrated broad application prospects of PLA/HA scaffolds with USCs in bone tissue engineering.


2020 ◽  
Vol 21 (16) ◽  
pp. 5816
Author(s):  
Kar Wey Yong ◽  
Jane Ru Choi ◽  
Jean Yu Choi ◽  
Alistair C. Cowie

Large bone defects are a major health concern worldwide. The conventional bone repair techniques (e.g., bone-grafting and Masquelet techniques) have numerous drawbacks, which negatively impact their therapeutic outcomes. Therefore, there is a demand to develop an alternative bone repair approach that can address the existing drawbacks. Bone tissue engineering involving the utilization of human mesenchymal stem cells (hMSCs) has recently emerged as a key strategy for the regeneration of damaged bone tissues. However, the use of tissue-engineered bone graft for the clinical treatment of bone defects remains challenging. While the role of mechanical loading in creating a bone graft has been well explored, the effects of mechanical loading factors (e.g., loading types and regime) on clinical outcomes are poorly understood. This review summarizes the effects of mechanical loading on hMSCs for bone tissue engineering applications. First, we discuss the key assays for assessing the quality of tissue-engineered bone grafts, including specific staining, as well as gene and protein expression of osteogenic markers. Recent studies of the impact of mechanical loading on hMSCs, including compression, perfusion, vibration and stretching, along with the potential mechanotransduction signalling pathways, are subsequently reviewed. Lastly, we discuss the challenges and prospects of bone tissue engineering applications.


Author(s):  
Magali Cruel ◽  
Morad Bensidhoum ◽  
Laure Sudre ◽  
Guillaume Puel ◽  
Virginie Dumas ◽  
...  

Bone tissue engineering currently represents one of the most interesting alternatives to autologous transplants and their drawbacks in the treatment of large bone defects. Mesenchymal stem cells are used to build new bone in vitro in a bioreactor. Their stimulation and our understanding of the mechanisms of mechanotransduction need to be improved in order to optimize the design of bioreactors. In this study, several geometries of bioreactor were analyzed experimentally and biological results were linked with numerical simulations of the flow inside the bioreactor. These results will constitute a base for an improved design of the existing bioreactor.


Author(s):  
Edney P. e Silva ◽  
Boyang Huang ◽  
Júlia V. Helaehil ◽  
Paulo R. L. Nalesso ◽  
Leonardo Bagne ◽  
...  

AbstractCritical bone defects are considered one of the major clinical challenges in reconstructive bone surgery. The combination of 3D printed conductive scaffolds and exogenous electrical stimulation (ES) is a potential favorable approach for bone tissue repair. In this study, 3D conductive scaffolds made with biocompatible and biodegradable polycaprolactone (PCL) and multi-walled carbon nanotubes (MWCNTs) were produced using the extrusion-based additive manufacturing to treat large calvary bone defects in rats. Histology results show that the use of PCL/MWCNTs scaffolds and ES contributes to thicker and increased bone tissue formation within the bone defect. Angiogenesis and mineralization are also significantly promoted using high concentration of MWCNTs (3 wt%) and ES. Moreover, scaffolds favor the tartrate-resistant acid phosphatase (TRAP) positive cell formation, while the addition of MWCNTs seems to inhibit the osteoclastogenesis but present limited effects on the osteoclast functionalities (receptor activator of nuclear factor κβ ligand (RANKL) and osteoprotegerin (OPG) expressions). The use of ES promotes the osteoclastogenesis and RANKL expressions, showing a dominant effect in the bone remodeling process. These results indicate that the combination of 3D printed conductive PCL/MWCNTs scaffold and ES is a promising strategy to treat critical bone defects and provide a cue to establish an optimal protocol to use conductive scaffolds and ES for bone tissue engineering.


2021 ◽  
Vol 22 (21) ◽  
pp. 11746
Author(s):  
Dušan Hollý ◽  
Martin Klein ◽  
Merita Mazreku ◽  
Radoslav Zamborský ◽  
Štefan Polák ◽  
...  

Oral and craniofacial bone defects caused by congenital disease or trauma are widespread. In the case of severe alveolar bone defect, autologous bone grafting has been considered a “gold standard”; however, the procedure has several disadvantages, including limited supply, resorption, donor site morbidity, deformity, infection, and bone graft rejection. In the last few decades, bone tissue engineering combined with stem cell-based therapy may represent a possible alternative to current bone augmentation techniques. The number of studies investigating different cell-based bone tissue engineering methods to reconstruct alveolar bone damage is rapidly rising. As an interdisciplinary field, bone tissue engineering combines the use of osteogenic cells (stem cells/progenitor cells), bioactive molecules, and biocompatible scaffolds, whereas stem cells play a pivotal role. Therefore, our work highlights the osteogenic potential of various dental tissue-derived stem cells and induced pluripotent stem cells (iPSCs), the progress in differentiation techniques of iPSCs into osteoprogenitor cells, and the efforts that have been made to fabricate the most suitable and biocompatible scaffold material with osteoinductive properties for successful bone graft generation. Moreover, we discuss the application of stem cell-derived exosomes as a compelling new form of “stem-cell free” therapy.


2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Gabriele Storti ◽  
Maria Giovanna Scioli ◽  
Bong-Sung Kim ◽  
Augusto Orlandi ◽  
Valerio Cervelli

Adipose stem cells (ASCs) are a crucial element in bone tissue engineering (BTE). They are easy to harvest and isolate, and they are available in significative quantities, thus offering a feasible and valid alternative to other sources of mesenchymal stem cells (MSCs), like bone marrow. Together with an advantageous proliferative and differentiative profile, they also offer a high paracrine activity through the secretion of several bioactive molecules (such as growth factors and miRNAs) via a sustained exosomal release which can exert efficient conditioning on the surrounding microenvironment. BTE relies on three key elements: (1) scaffold, (2) osteoprogenitor cells, and (3) bioactive factors. These elements have been thoroughly investigated over the years. The use of ASCs has offered significative new advancements in the efficacy of each of these elements. Notably, the phenotypic study of ASCs allowed discovering cell subpopulations, which have enhanced osteogenic and vasculogenic capacity. ASCs favored a better vascularization and integration of the scaffolds, while improvements in scaffolds’ materials and design tried to exploit the osteogenic features of ASCs, thus reducing the need for external bioactive factors. At the same time, ASCs proved to be an incredible source of bioactive, proosteogenic factors that are released through their abundant exosome secretion. ASC exosomes can exert significant paracrine effects in the surroundings, even in the absence of the primary cells. These paracrine signals recruit progenitor cells from the host tissues and enhance regeneration. In this review, we will focus on the recent discoveries which have involved the use of ASCs in BTE. In particular, we are going to analyze the different ASCs’ subpopulations, the interaction between ASCs and scaffolds, and the bioactive factors which are secreted by ASCs or can induce their osteogenic commitment. All these advancements are ultimately intended for a faster translational and clinical application of BTE.


Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2687
Author(s):  
Venkata Suresh Venkataiah ◽  
Yoshio Yahata ◽  
Akira Kitagawa ◽  
Masahiko Inagaki ◽  
Yusuke Kakiuchi ◽  
...  

Bone tissue engineering (BTE) is a process of combining live osteoblast progenitors with a biocompatible scaffold to produce a biological substitute that can integrate into host bone tissue and recover its function. Mesenchymal stem cells (MSCs) are the most researched post-natal stem cells because they have self-renewal properties and a multi-differentiation capacity that can give rise to various cell lineages, including osteoblasts. BTE technology utilizes a combination of MSCs and biodegradable scaffold material, which provides a suitable environment for functional bone recovery and has been developed as a therapeutic approach to bone regeneration. Although prior clinical trials of BTE approaches have shown promising results, the regeneration of large bone defects is still an unmet medical need in patients that have suffered a significant loss of bone function. In this present review, we discuss the osteogenic potential of MSCs in bone tissue engineering and propose the use of immature osteoblasts, which can differentiate into osteoblasts upon transplantation, as an alternative cell source for regeneration in large bone defects.


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