scholarly journals Mesenchymal Stem Cells, Bioactive Factors, and Scaffolds in Bone Repair: From Research Perspectives to Clinical Practice

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1925
Author(s):  
Sandra Stamnitz ◽  
Aleksandra Klimczak
Keyword(s):  
Tissue Engineering ◽  
Stem Cell ◽  
Bone Tissue ◽  
Bone Repair ◽  
Bone Tissue Regeneration ◽  
Research Perspective ◽  
Stem Cell Source ◽  
Research Perspectives ◽  
In Vivo Animal Model

Mesenchymal stem cell-based therapies are promising tools for bone tissue regeneration. However, tracking cells and maintaining them in the site of injury is difficult. A potential solution is to seed the cells onto a biocompatible scaffold. Construct development in bone tissue engineering is a complex step-by-step process with many variables to be optimized, such as stem cell source, osteogenic molecular factors, scaffold design, and an appropriate in vivo animal model. In this review, an MSC-based tissue engineering approach for bone repair is reported. Firstly, MSC role in bone formation and regeneration is detailed. Secondly, MSC-based bone tissue biomaterial design is analyzed from a research perspective. Finally, examples of animal preclinical and human clinical trials involving MSCs and scaffolds in bone repair are presented.

scholarly journals Continuum Modeling and Simulation in Bone Tissue Engineering

2019 ◽  
Vol 9 (18) ◽  
pp. 3674 ◽  
Author(s):  
Jose A. Sanz-Herrera ◽  
Esther Reina-Romo
Keyword(s):  
Tissue Engineering ◽  
Modeling And Simulation ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
In Silico ◽  
Assessment Tool ◽  
Numerical Models ◽  
Research Perspective

Bone tissue engineering is currently a mature methodology from a research perspective. Moreover, modeling and simulation of involved processes and phenomena in BTE have been proved in a number of papers to be an excellent assessment tool in the stages of design and proof of concept through in-vivo or in-vitro experimentation. In this paper, a review of the most relevant contributions in modeling and simulation, in silico, in BTE applications is conducted. The most popular in silico simulations in BTE are classified into: (i) Mechanics modeling and scaffold design, (ii) transport and flow modeling, and (iii) modeling of physical phenomena. The paper is restricted to the review of the numerical implementation and simulation of continuum theories applied to different processes in BTE, such that molecular dynamics or discrete approaches are out of the scope of the paper. Two main conclusions are drawn at the end of the paper: First, the great potential and advantages that in silico simulation offers in BTE, and second, the need for interdisciplinary collaboration to further validate numerical models developed in BTE.

scholarly journals Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

2017 ◽  
Vol 8 ◽  
pp. 204173141771207 ◽  
Author(s):  
Mathieu Maisani ◽  
Daniele Pezzoli ◽  
Olivier Chassande ◽  
Diego Mantovani
Keyword(s):  
Bone Regeneration ◽  
Bone Tissue ◽  
Bone Repair ◽  
Critical Issue ◽  
Bone Defects ◽  
Bone Tissue Regeneration ◽  
Differentiation Potential ◽  
Promising Alternative

Tissue engineering is a promising alternative to autografts or allografts for the regeneration of large bone defects. Cell-free biomaterials with different degrees of sophistication can be used for several therapeutic indications, to stimulate bone repair by the host tissue. However, when osteoprogenitors are not available in the damaged tissue, exogenous cells with an osteoblast differentiation potential must be provided. These cells should have the capacity to colonize the defect and to participate in the building of new bone tissue. To achieve this goal, cells must survive, remain in the defect site, eventually proliferate, and differentiate into mature osteoblasts. A critical issue for these engrafted cells is to be fed by oxygen and nutrients: the transient absence of a vascular network upon implantation is a major challenge for cells to survive in the site of implantation, and different strategies can be followed to promote cell survival under poor oxygen and nutrient supply and to promote rapid vascularization of the defect area. These strategies involve the use of scaffolds designed to create the appropriate micro-environment for cells to survive, proliferate, and differentiate in vitro and in vivo. Hydrogels are an eclectic class of materials that can be easily cellularized and provide effective, minimally invasive approaches to fill bone defects and favor bone tissue regeneration. Furthermore, by playing on their composition and processing, it is possible to obtain biocompatible systems with adequate chemical, biological, and mechanical properties. However, only a good combination of scaffold and cells, possibly with the aid of incorporated growth factors, can lead to successful results in bone regeneration. This review presents the strategies used to design cellularized hydrogel-based systems for bone regeneration, identifying the key parameters of the many different micro-environments created within hydrogels.

scholarly journals Prospect of Stem Cells in Bone Tissue Engineering: A Review

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Azizeh-Mitra Yousefi ◽  
Paul F. James ◽  
Rosa Akbarzadeh ◽  
Aswati Subramanian ◽  
Conor Flavin ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Cell Types ◽  
3D Scaffold ◽  
Stem Cell Source ◽  
Induced Pluripotent

Mesenchymal stem cells (MSCs) have been the subject of many studies in recent years, ranging from basic science that looks into MSCs properties to studies that aim for developing bioengineered tissues and organs. Adult bone marrow-derived mesenchymal stem cells (BM-MSCs) have been the focus of most studies due to the inherent potential of these cells to differentiate into various cell types. Although, the discovery of induced pluripotent stem cells (iPSCs) represents a paradigm shift in our understanding of cellular differentiation. These cells are another attractive stem cell source because of their ability to be reprogramed, allowing the generation of multiple cell types from a single cell. This paper briefly covers various types of stem cell sources that have been used for tissue engineering applications, with a focus on bone regeneration. Then, an overview of some recent studies making use of MSC-seeded 3D scaffold systems for bone tissue engineering has been presented. The emphasis has been placed on the reported scaffold properties that tend to improve MSCs adhesion, proliferation, and osteogenic differentiation outcomes.

scholarly journals Conducting PEEK Nanocomposites with Electrophoretically Deposited Bioactive Coating for Bone Tissue Regeneration and Multi-Modal Therapeutic Applications

2020 ◽  
Author(s):  
Miaomiao He ◽  
Ce zhu ◽  
Huan Xu ◽  
dan Sun ◽  
Chen Chen ◽  
...  
Keyword(s):  
Bone Tissue ◽  
Tissue Regeneration ◽  
Bone Repair ◽  
Graphene Nanosheets ◽  
Biomechanical Properties ◽  
Bone Diseases ◽  
Bone Tissue Regeneration ◽  
Order Of Magnitude

The use of polyetheretherketone (PEEK) has grown exponentially in the biomedical field in recent decades due to its outstanding biomechanical properties. However, its lack of bioactivity/osteointegration remains an unresolved issue towards its wide use in orthopedic applications. In this work, graphene nanosheets have been incorporated into PEEK to obtain multifunctional nanocomposites. Due to the formation of electrical percolation network and the π-π* conjugation between graphene and PEEK, the resulting composites have achieved twelve order of magnitude enhancement in its electrical conductivity, and have enabled electrophoretic deposition of bioactive/anti-bacterial coating consisting of stearyltrimethylammonium chloride (STAC) modified hydroxyapatite (HA). The coated composite implant showed significant boosting of BMSC cell proliferation in vitro. In addition, the strong photothermal conversion effect of the graphene nanofillers have enabled laser induced heating of our nanocomposite implants, where the temperature of the implant can reach 45 oC in 150 s. The unique multi-functionality of our composite implant has also been demonstrated for photothermal applications such as enhancing bacterial (E. coli and S. aureus) eradication and tumor cell (MG63) inhibition, as well as bone tissue regeneration in vivo. The results suggest the strong potential of our multi-functional implant in bone repair applications as well as multi-modal therapy of challenging bone diseases such as osteosarcoma and osteomyelitis

scholarly journals Skeletal Stem Cells—A Paradigm Shift in the Field of Craniofacial Bone Tissue Engineering

2020 ◽  
Vol 1 ◽  
Author(s):  
Ruth Tevlin ◽  
Michael T. Longaker ◽  
Derrick C. Wan
Keyword(s):  
Tissue Engineering ◽  
Stem Cell ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Systemic Disease ◽  
Direct Result ◽  
Craniofacial Skeleton ◽  
Craniofacial Bone

Defects of the craniofacial skeleton arise as a direct result of trauma, diseases, oncological resection, or congenital anomalies. Current treatment options are limited, highlighting the importance for developing new strategies to restore form, function, and aesthetics of missing or damaged bone in the face and the cranium. For optimal reconstruction, the goal is to replace “like with like.” With the inherent challenges of existing options, there is a clear need to develop alternative strategies to reconstruct the craniofacial skeleton. The success of mesenchymal stem cell-based approaches has been hampered by high heterogeneity of transplanted cell populations with inconsistent preclinical and clinical trial outcomes. Here, we discuss the novel characterization and isolation of mouse skeletal stem cell (SSC) populations and their response to injury, systemic disease, and how their re-activation in vivo can contribute to tissue regeneration. These studies led to the characterization of human SSCs which are able to self-renew, give rise to increasingly fate restricted progenitors, and differentiate into bone, cartilage, and bone marrow stroma, all on the clonal level in vivo without prior in vitro culture. SSCs hold great potential for implementation in craniofacial bone tissue engineering and regenerative medicine. As we begin to better understand the diversity and the nature of skeletal stem and progenitor cells, there is a tangible future whereby a subset of human adult SSCs can be readily purified from bone or activated in situ with broad potential applications in craniofacial tissue engineering.

scholarly journals A review of chitosan-, alginate-, and gelatin-based biocomposites for bone tissue engineering

2018 ◽  
Vol 5 (3-4) ◽  
pp. 97-109 ◽  
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Bone Repair ◽  
Bone Diseases ◽  
Natural Polymers ◽  
Antimicrobial Substances ◽  
Potential Applications

Bone diseases and injuries have a major impact on the quality of life. Classical treatments for bone repair/regeneration/replacement have various disadvantages. Bone tissue engineering (BTE) received a great attention in the last years. Natural polymers are intensively studied in this field due to their properties (biocompatibility, biodegradability, abundance in nature, high processability). Unfortunately, their mechanical properties are poor, which is why synthetic polymers or ceramics are added in order to provide the optimal compressive, elastic or fatigue strength. Moreover, growth factors, vitamins, or antimicrobial substances are also added to enhance the cell behavior (attachment, proliferation, and differentiation). In this review, new scientific results regarding potential applications of chitosan-, alginate-, and gelatin based biocomposites in BTE will be provided, along with their in vitro and/or in vivo tests.

scholarly journals Natural and Synthetic Polymers for Bone Scaffolds Optimization

Polymers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 905 ◽  
Author(s):  
Francesca Donnaloja ◽  
Emanuela Jacchetti ◽  
Monica Soncini ◽  
Manuela T. Raimondi
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue ◽  
Bone Cells ◽  
The Body ◽  
Bone Tissue Regeneration ◽  
In Vivo Models ◽  
Polymeric Scaffold ◽  
Technology Improvement

Bone tissue is the structural component of the body, which allows locomotion, protects vital internal organs, and provides the maintenance of mineral homeostasis. Several bone-related pathologies generate critical-size bone defects that our organism is not able to heal spontaneously and require a therapeutic action. Conventional therapies span from pharmacological to interventional methodologies, all of them characterized by several drawbacks. To circumvent these effects, tissue engineering and regenerative medicine are innovative and promising approaches that exploit the capability of bone progenitors, especially mesenchymal stem cells, to differentiate into functional bone cells. So far, several materials have been tested in order to guarantee the specific requirements for bone tissue regeneration, ranging from the material biocompatibility to the ideal 3D bone-like architectural structure. In this review, we analyse the state-of-the-art of the most widespread polymeric scaffold materials and their application in in vitro and in vivo models, in order to evaluate their usability in the field of bone tissue engineering. Here, we will present several adopted strategies in scaffold production, from the different combination of materials, to chemical factor inclusion, embedding of cells, and manufacturing technology improvement.

scholarly journals An ECM-Mimicking, Mesenchymal Stem Cell-Embedded Hybrid Scaffold for Bone Regeneration

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Jozafina Haj ◽  
Tharwat Haj Khalil ◽  
Mizied Falah ◽  
Eyal Zussman ◽  
Samer Srouji
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Bone Tissue Engineering ◽  
Bone Regeneration ◽  
Bone Tissue ◽  
Bone Repair ◽  
Dorsal Side ◽  
Human Mscs ◽  
Hybrid Scaffold

While biologically feasible, bone repair is often inadequate, particularly in cases of large defects. The search for effective bone regeneration strategies has led to the emergence of bone tissue engineering (TE) techniques. When integrating electrospinning techniques, scaffolds featuring randomly oriented or aligned fibers, characteristic of the extracellular matrix (ECM), can be fabricated. In parallel, mesenchymal stem cells (MSCs), which are capable of both self-renewing and differentiating into numerous tissue types, have been suggested to be a suitable option for cell-based tissue engineering therapies. This work aimed to create a novel biocompatible hybrid scaffold composed of electrospun polymeric nanofibers combined with osteoconductive ceramics, loaded with human MSCs, to yield a tissue-like construct to promote in vivo bone formation. Characterization of the cell-embedded scaffolds demonstrated their resemblance to bone tissue extracellular matrix, on both micro- and nanoscales and MSC viability and integration within the electrospun nanofibers. Subcutaneous implantation of the cell-embedded scaffolds in the dorsal side of mice led to new bone, muscle, adipose, and connective tissue formation within 8 weeks. This hybrid scaffold may represent a step forward in the pursuit of advanced bone tissue engineering scaffolds.

scholarly journals Bone Tissue Regeneration by Collagen Scaffolds with Different Calcium Phosphate Coatings: Amorphous Calcium Phosphate and Low-Crystalline Apatite

Materials ◽  
2021 ◽  
Vol 14 (19) ◽  
pp. 5860
Author(s):  
Syama Santhakumar ◽  
Ayako Oyane ◽  
Maki Nakamura ◽  
Yuto Yoshino ◽  
Mohammed Katib Alruwaili ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Calcium Phosphate ◽  
Bone Tissue ◽  
Tissue Regeneration ◽  
Amorphous Calcium Phosphate ◽  
Bone Tissue Regeneration ◽  
Apatite Coating ◽  
Low Crystalline ◽  
Mineralized Collagen

Surface-mineralized collagen sponges have attracted much attention as scaffolds for bone tissue engineering. Recently, we developed amorphous calcium phosphate (ACP) and low-crystalline apatite coating processes on collagen sponges. In the present study, we applied these coating processes to granular collagen sponges (referred to as Col) to compare the bone tissue regeneration capabilities of ACP-coated and apatite-coated Col (referred to as Col-ACP and Col-Ap, respectively) using a rat cranial bone defect model. According to micro-CT and histological analyses, Col-Ap enhanced bone tissue regeneration compared to Col, whereas Col-ACP did not. These results not only demonstrated the superior bone tissue regeneration capability of Col-Ap, but also indicated limitations of the in vitro simulated body fluid (SBF) test used in our previous study. Despite the apatite-forming ability of Col-ACP in SBF, it was ineffective in improving bone tissue regeneration in vivo, unlike Col-Ap, most likely due to the quick resorption of the ACP coating in the defect site. The present results clarified the importance of the coating stability in vivo and revealed that the low-crystalline apatite coating was more beneficial than the ACP coating in the fabrication of surface-mineralized collagen sponges for use as bone tissue engineering scaffolds.

scholarly journals Scaffold-free human mesenchymal stem cell construct geometry regulates long bone regeneration

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Samuel Herberg ◽  
Daniel Varghai ◽  
Daniel S. Alt ◽  
Phuong N. Dang ◽  
Honghyun Park ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Human Mesenchymal Stem Cell ◽  
Functional Restoration ◽  
Defect Healing ◽  
Tgf Β1

AbstractBiomimetic bone tissue engineering strategies partially recapitulate development. We recently showed functional restoration of femoral defects using scaffold-free human mesenchymal stem cell (hMSC) condensates featuring localized morphogen presentation with delayed in vivo mechanical loading. Possible effects of construct geometry on healing outcome remain unclear. Here, we hypothesized that localized presentation of transforming growth factor (TGF)-β1 and bone morphogenetic protein (BMP)-2 to engineered hMSC tubes mimicking femoral diaphyses induces endochondral ossification, and that TGF-β1 + BMP-2-presenting hMSC tubes enhance defect healing with delayed in vivo loading vs. loosely packed hMSC sheets. Localized morphogen presentation stimulated chondrogenic priming/endochondral differentiation in vitro. Subcutaneously, hMSC tubes formed cartilage templates that underwent bony remodeling. Orthotopically, hMSC tubes stimulated more robust endochondral defect healing vs. hMSC sheets. Tissue resembling normal growth plate was observed with negligible ectopic bone. This study demonstrates interactions between hMSC condensation geometry, morphogen bioavailability, and mechanical cues to recapitulate development for biomimetic bone tissue engineering.

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