Human Oral Stem Cells, Biomaterials and Extracellular Vesicles: A Promising Tool in Bone Tissue Repair

Tissue engineering and/or regenerative medicine are fields of life science exploiting both engineering and biological fundamentals to originate new tissues and organs and to induce the regeneration of damaged or diseased tissues and organs. In particular, de novo bone tissue regeneration requires a mechanically competent osteo-conductive/inductive 3D biomaterial scaffold that guarantees the cell adhesion, proliferation, angiogenesis and differentiation into osteogenic lineage. Cellular components represent a key factor in tissue engineering and bone growth strategies take advantage from employment of mesenchymal stem cells (MSCs), an ideal cell source for tissue repair. Recently, the application of extracellular vesicles (EVs), isolated from stem cells, as cell-free therapy has emerged as a promising therapeutic strategy. This review aims at summarizing the recent and representative research on the bone tissue engineering field using a 3D scaffold enriched with human oral stem cells and their derivatives, EVs, as a promising therapeutic potential in the reconstructing of bone tissue defects.

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Bone Tissue Regeneration in the Oral and Maxillofacial Region: A Review on the Application of Stem Cells and New Strategies to Improve Vascularization

Stem Cells International ◽

10.1155/2019/6279721 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15 ◽

Cited By ~ 8

Author(s):

Vivian Wu ◽

Marco N. Helder ◽

Nathalie Bravenboer ◽

Christiaan M. ten Bruggenkate ◽

Jianfeng Jin ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Tissue Regeneration ◽

Host Tissue ◽

Bone Tissue Regeneration ◽

Maxillofacial Region ◽

Oral And Maxillofacial Region ◽

New Strategies

Bone tissue engineering techniques are a promising alternative for the use of autologous bone grafts to reconstruct bone defects in the oral and maxillofacial region. However, for successful bone regeneration, adequate vascularization is a prerequisite. This review presents and discusses the application of stem cells and new strategies to improve vascularization, which may lead to feasible clinical applications. Multiple sources of stem cells have been investigated for bone tissue engineering. The stromal vascular fraction (SVF) of human adipose tissue is considered a promising single source for a heterogeneous population of essential cells with, amongst others, osteogenic and angiogenic potential. Enhanced vascularization of tissue-engineered grafts can be achieved by different mechanisms: vascular ingrowth directed from the surrounding host tissue to the implanted graft, vice versa, or concomitantly. Vascular ingrowth into the implanted graft can be enhanced by (i) optimizing the material properties of scaffolds and (ii) their bioactivation by incorporation of growth factors or cell seeding. Vascular ingrowth directed from the implanted graft towards the host tissue can be achieved by incorporating the graft with either (i) preformed microvascular networks or (ii) microvascular fragments (MF). The latter may have stimulating actions on both vascular ingrowth and outgrowth, since they contain angiogenic stem cells like SVF, as well as vascularized matrix fragments. Both adipose tissue-derived SVF and MF are cell sources with clinical feasibility due to their large quantities that can be harvested and applied in a one-step surgical procedure. During the past years, important advancements of stem cell application and vascularization in bone tissue regeneration have been made. The development of engineered in vitro 3D models mimicking the bone defect environment would facilitate new strategies in bone tissue engineering. Successful clinical application requires innovative future investigations enhancing vascularization.

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Design of Tissue Engineering Implants for Bone Tissue Regeneration of the Basis of New Generation Polylactoglycolide Scaffolds and Multipotent Mesenchymal Stem Cells from Human Exfoliated Deciduous Teeth (SHED Cells)

Bulletin of Experimental Biology and Medicine ◽

10.1007/s10517-012-1663-2 ◽

2012 ◽

Vol 153 (1) ◽

pp. 143-147 ◽

Cited By ~ 13

Author(s):

I. V. Vakhrushev ◽

E. N. Antonov ◽

A. V. Popova ◽

E. V. Konstantinova ◽

P. A. Karalkin ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Bone Tissue ◽

Tissue Regeneration ◽

Bone Tissue Regeneration ◽

Deciduous Teeth ◽

Multipotent Mesenchymal Stem Cells ◽

New Generation ◽

Human Exfoliated Deciduous Teeth

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Oral Bone Tissue Regeneration: Mesenchymal Stem Cells, Secretome, and Biomaterials

International Journal of Molecular Sciences ◽

10.3390/ijms22105236 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5236

Author(s):

Agnese Gugliandolo ◽

Luigia Fonticoli ◽

Oriana Trubiani ◽

Thangavelu S. Rajan ◽

Guya D. Marconi ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Bone Regeneration ◽

Bone Tissue ◽

Tissue Regeneration ◽

Functional Restoration ◽

Bone Tissue Regeneration ◽

In Vivo Models

In the last few decades, tissue engineering has become one of the most studied medical fields. Even if bone shows self-remodeling properties, in some cases, due to injuries or anomalies, bone regeneration can be required. In particular, oral bone regeneration is needed in the dentistry field, where the functional restoration of tissues near the tooth represents a limit for many dental implants. In this context, the application of biomaterials and mesenchymal stem cells (MSCs) appears promising for bone regeneration. This review focused on in vivo studies that evaluated bone regeneration using biomaterials with MSCs. Different biocompatible biomaterials were enriched with MSCs from different sources. These constructs showed an enhanced bone regenerative power in in vivo models. However, we discussed also a future perspective in tissue engineering using the MSC secretome, namely the conditioned medium and extracellular vesicles. This new approach has already shown promising results for bone tissue regeneration in experimental models.

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SYNTHESIS OF MICRO- AND NANOSIZED BIORESORBING SILICON-SUBSTITUTED TRICALCIUM PHOSPHATES FOR BONE TISSUE ENGINEERING AND THEIR BIOLOGICAL SAFETY USING MESENCHYMAL STEM CELLS

Nanomechanics Science and Technology An International Journal ◽

10.1615/nanomechanicsscitechnolintj.v6.i4.50 ◽

2015 ◽

Vol 6 (4) ◽

pp. 305-317

Author(s):

I. V. Fadeeva ◽

Ya. Yu. Filippov ◽

A. S. Fomin ◽

M. E. Shaposhnikov ◽

G. A. Davydova ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Biological Safety ◽

Tricalcium Phosphates

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Faculty Opinions recommendation of Endochondral bone tissue engineering using embryonic stem cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1111103.574974 ◽

2008 ◽

Author(s):

Paolo Bianco ◽

Mara Riminucci

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Embryonic Stem Cells ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Embryonic Stem ◽

Endochondral Bone

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Dual Network Composites of Poly(vinyl alcohol)-Calcium Metaphosphate/Alginate with Osteogenic Ions for Bone Tissue Engineering in Oral and Maxillofacial Surgery

Bioengineering ◽

10.3390/bioengineering8080107 ◽

2021 ◽

Vol 8 (8) ◽

pp. 107

Author(s):

Lilis Iskandar ◽

Lucy DiSilvio ◽

Jonathan Acheson ◽

Sanjukta Deb

Keyword(s):

Tissue Engineering ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Vinyl Alcohol ◽

Maxillofacial Surgery ◽

Bone Defects ◽

Bone Tissue Regeneration ◽

Poly Vinyl Alcohol ◽

Oral And Maxillofacial Surgery

Despite considerable advances in biomaterials-based bone tissue engineering technologies, autografts remain the gold standard for rehabilitating critical-sized bone defects in the oral and maxillofacial (OMF) region. A majority of advanced synthetic bone substitutes (SBS’s) have not transcended the pre-clinical stage due to inferior clinical performance and translational barriers, which include low scalability, high cost, regulatory restrictions, limited advanced facilities and human resources. The aim of this study is to develop clinically viable alternatives to address the challenges of bone tissue regeneration in the OMF region by developing ‘dual network composites’ (DNC’s) of calcium metaphosphate (CMP)—poly(vinyl alcohol) (PVA)/alginate with osteogenic ions: calcium, zinc and strontium. To fabricate DNC’s, single network composites of PVA/CMP with 10% (w/v) gelatine particles as porogen were developed using two freeze–thawing cycles and subsequently interpenetrated by guluronate-dominant sodium alginate and chelated with calcium, zinc or strontium ions. Physicochemical, compressive, water uptake, thermal, morphological and in vitro biological properties of DNC’s were characterised. The results demonstrated elastic 3D porous scaffolds resembling a ‘spongy bone’ with fluid absorbing capacity, easily sculptable to fit anatomically complex bone defects, biocompatible and osteoconductive in vitro, thus yielding potentially clinically viable for SBS alternatives in OMF surgery.

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Osteogenic potential of dental and oral derived stem cells in bone tissue engineering among animal models: An update

Tissue and Cell ◽

10.1016/j.tice.2021.101515 ◽

2021 ◽

Vol 71 ◽

pp. 101515

Author(s):

Antoine Berbéri ◽

Mohammad Fayyad-kazan ◽

Sara Ayoub ◽

Rita Bou Assaf ◽

Joseph Sabbagh ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Animal Models ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Osteogenic Potential

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A novel gelatin/chitooligosaccharide/demineralized bone matrix composite scaffold and periosteum-derived mesenchymal stem cells for bone tissue engineering

Biomaterials Research ◽

10.1186/s40824-021-00220-y ◽

2021 ◽

Vol 25 (1) ◽

Author(s):

Thakoon Thitiset ◽

Siriporn Damrongsakkul ◽

Supansa Yodmuang ◽

Wilairat Leeanansaksiri ◽

Jirun Apinun ◽

...

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Bone Formation ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Demineralized Bone Matrix ◽

Bone Matrix ◽

Alp Activity

Abstract Background A novel biodegradable scaffold including gelatin (G), chitooligosaccharide (COS), and demineralized bone matrix (DBM) could play a significant part in bone tissue engineering. The present study aimed to investigate the biological characteristics of composite scaffolds in combination of G, COS, and DBM for in vitro cell culture and in vivo animal bioassays. Methods Three-dimensional scaffolds from the mixture of G, COS, and DBM were fabricated into 3 groups, namely, G, GC, and GCD using a lyophilization technique. The scaffolds were cultured with mesenchymal stem cells (MSCs) for 4 weeks to determine biological responses such as cell attachment and cell proliferation, alkaline phosphatase (ALP) activity, calcium deposition, cell morphology, and cell surface elemental composition. For the in vivo bioassay, G, GC, and GCD, acellular scaffolds were implanted subcutaneously in 8-week-old male Wistar rats for 4 weeks and 8 weeks. The explants were assessed for new bone formation using hematoxylin and eosin (H&E) staining and von Kossa staining. Results The MSCs could attach and proliferate on all three groups of scaffolds. Interestingly, the ALP activity of MSCs reached the greatest value on day 7 after cultured on the scaffolds, whereas the calcium assay displayed the highest level of calcium in MSCs on day 28. Furthermore, weight percentages of calcium and phosphorus on the surface of MSCs after cultivation on the GCD scaffolds increased when compared to those on other scaffolds. The scanning electron microscopy images showed that MSCs attached and proliferated on the scaffold surface thoroughly over the cultivation time. Mineral crystal aggregation was evident in GC and greatly in GCD scaffolds. H&E staining illustrated that G, GC, and GCD scaffolds displayed osteoid after 4 weeks of implantation and von Kossa staining confirmed the mineralization at 8 weeks in G, GC, and GCD scaffolds. Conclusion The MSCs cultured in GCD scaffolds revealed greater osteogenic differentiation than those cultured in G and GC scaffolds. Additionally, the G, GC, and GCD scaffolds could promote in vivo ectopic bone formation in rat model. The GCD scaffolds exhibited maximum osteoinductive capability compared with others and may be potentially used for bone regeneration.

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A Bibliometric Analysis of the Global Trend of Using Alginate, Gelatine, and Hydroxyapatite for Bone Tissue Regeneration Applications

Polymers ◽

10.3390/polym13040647 ◽

2021 ◽

Vol 13 (4) ◽

pp. 647

Author(s):

Mohamed Saiful Firdaus Hussin ◽

Aludin Mohd Serah ◽

Khairul Azri Azlan ◽

Hasan Zuhudi Abdullah ◽

Maizlinda Izwana Idris ◽

...

Keyword(s):

Tissue Engineering ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Bibliometric Analysis ◽

Research Work ◽

The United States ◽

Research Area ◽

Bone Tissue Regeneration ◽

Future Research ◽

Starting Point

Collecting information from previous investigations and expressing it in a scientometrics study can be a priceless guide to getting a complete overview of a specific research area. The aim of this study is to explore the interrelated connection between alginate, gelatine, and hydroxyapatite within the scope of bone tissue and scaffold. A review of traditional literature with data mining procedures using bibliometric analyses was considered to identify the evolution of the selected research area between 2009 and 2019. Bibliometric methods and knowledge visualization technologies were implemented to investigate diverse publications based on the following indicators: year of publication, document type, language, country, institution, author, journal, keyword, and number of citations. An analysis using a bibliometric study found that 7446 papers were located with the keywords “bone tissue” and “scaffold”, and 1767 (alginate), 185 (gelatine), 5658 (hydroxyapatite) papers with those specific sub keywords. The number of publications that relate to “tissue engineering” and bone more than doubled between 2009 (1352) and 2019 (2839). China, the United States and India are the most productive countries, while Sichuan University and the Chinese Academy of Science from China are the most important institutions related to bone tissue scaffold. Materials Science and Engineering C is the most productive journal, followed by the Journal of Biomedical Materials Research Part A. This paper is a starting point, providing the first bibliometric analysis study of bone tissue and scaffold considering alginate, gelatine and hydroxyapatite. A bibliometric analysis would greatly assist in giving a scientific insight to support desired future research work, not only associated with bone tissue engineering applications. It is expected that the analysis of alginate, gelatine and hydroxyapatite in terms of 3D bioprinting, clinical outcomes, scaffold architecture, and the regenerative medicine approach will enhance the research into bone tissue engineering in the near future. Continued studies into these research fields are highly recommended.

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