Effect of different growth factors on human osteoblasts activities: A possible application in bone regeneration for tissue engineering

Bone tissue renewal can be outlined as a complicated mechanism centered on the interaction between osteogenic and angiogenic events capable of leading to bone formation and tissue renovation. The achievement or debacle of bone regeneration is focused on the primary role of vascularization occurrence; in particular, the turning point is the opportunity to vascularize the bulk scaffolds, in order to deliver enough nutrients, growth factors, minerals and oxygen for tissue restoration. The optimal scaffolds should ensure the development of vascular networks to warrant a positive suitable microenvironment for tissue engineering and renewal. Vascular Endothelial Growth Factor (VEGF), a main player in angiogenesis, is capable of provoking the migration and proliferation of endothelial cells and indirectly stimulating osteogenesis, through the regulation of the osteogenic growth factors released and through paracrine signaling. For this reason, we concentrated our attention on two principal groups involved in the renewal of bone tissue defects: the cells and the scaffold that should guarantee an effective vascularization process. The application of Mesenchymal Stem Cells (MSCs), an excellent cell source for tissue restoration, evidences a crucial role in tissue engineering and bone development strategies. This review aims to provide an overview of the intimate connection between blood vessels and bone formation that appear during bone regeneration when MSCs, their secretome—Extracellular Vesicles (EVs) and microRNAs (miRNAs) —and bone substitutes are used in combination.

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Effects of Growth Factors and Stress Conditioning on the Induction of Heat Shock Proteins and Osteogenesis

ASME 2009 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2009-206662 ◽

2009 ◽

Author(s):

Eunna Chung ◽

Marissa Nichole Rylander

Keyword(s):

Tissue Engineering ◽

Growth Factors ◽

Heat Shock ◽

Heat Shock Proteins ◽

Tensile Stress ◽

Bone Regeneration ◽

Tissue Regeneration ◽

Stress Conditioning ◽

Shock Proteins ◽

Related Proteins

Tissue engineering is an emerging field that focuses on development of methods for repairing and regenerating damaged or diseased tissue. Successful development of engineered tissues is often limited by insufficient cellular proliferation and insufficient formation of extracellular matrix. To induce effective bone regeneration, many research groups have investigated the cellular response and capability for tissue regeneration associated with bioreactor conditions and addition of growth factors [1]. Bioreactors in tissue engineering have been developed to expose cells to a similar stress environment as found within the body or induce elevated stress levels for potential induction of specific cellular responses associated with tissue regeneration. Native bone encounters a diverse array of dynamic stresses such as shear, tensile, and compression daily. Stress conditioning protocols in the form of thermal or tensile stress have been shown to induce up-regulation of molecular chaperones called heat shock proteins (HSPs) and bone-related proteins like MMP13 (matrix metallopeptidase 13) [2] and OPG (osteoprotegerin) [3, 4]. HSPs have important roles in enhancing cell proliferation and collagen synthesis. Osteogenic growth factors such as TGF-β1 (transforming growth factor beta 1) and BMP-2 (bone morphogenetic protein 2) are related to bone remodeling and osteogenesis as well as HSP induction [5]. Therefore, identification of effective preconditioning using growth factors and stress protocols that enhance HSP expression could substantially advance development of bone regeneration. The purpose of this research was to identify preconditioning protocols using osteogenic growth factors and tensile stress applied through a bioreactor system to enhance expression of HSPs and bone-related proteins while minimizing cellular injury for ultimate use for bone regeneration.

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An in situ tissue engineering scaffold with growth factors combining angiogenesis and osteoimmunomodulatory functions for advanced periodontal bone regeneration

Journal of Nanobiotechnology ◽

10.1186/s12951-021-00992-4 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Tian Ding ◽

Wenyan Kang ◽

Jianhua Li ◽

Lu Yu ◽

Shaohua Ge

Keyword(s):

Tissue Engineering ◽

Growth Factors ◽

Bone Regeneration ◽

Bone Defect ◽

Bone Repair ◽

Macrophage Polarization ◽

Tissue Engineering Scaffold ◽

Bone Morphogenetic Protein 2 ◽

In Situ Tissue Engineering

Abstract Background The regeneration of periodontal bone defect remains a vital clinical challenge. To date, numerous biomaterials have been applied in this field. However, the immune response and vascularity in defect areas may be key factors that are overlooked when assessing the bone regeneration outcomes of biomaterials. Among various regenerative therapies, the up-to-date strategy of in situ tissue engineering stands out, which combined scaffold with specific growth factors that could mimic endogenous regenerative processes. Results Herein, we fabricated a core/shell fibrous scaffold releasing basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2) in a sequential manner and investigated its immunomodulatory and angiogenic properties during periodontal bone defect restoration. The in situ tissue engineering scaffold (iTE-scaffold) effectively promoted the angiogenesis of periodontal ligament stem cells (PDLSCs) and induced macrophage polarization into pro-healing M2 phenotype to modulate inflammation. The immunomodulatory effect of macrophages could further promote osteogenic differentiation of PDLSCs in vitro. After being implanted into the periodontal bone defect model, the iTE-scaffold presented an anti-inflammatory response, provided adequate blood supply, and eventually facilitated satisfactory periodontal bone regeneration. Conclusions Our results suggested that the iTE-scaffold exerted admirable effects on periodontal bone repair by modulating osteoimmune environment and angiogenic activity. This multifunctional scaffold holds considerable promise for periodontal regenerative medicine and offers guidance on designing functional biomaterials. Graphic Abstract

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Strategies for Bone Regeneration: From Graft to Tissue Engineering

International Journal of Molecular Sciences ◽

10.3390/ijms22031128 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1128

Author(s):

Giulia Battafarano ◽

Michela Rossi ◽

Viviana De Martino ◽

Francesco Marampon ◽

Luca Borro ◽

...

Keyword(s):

Tissue Engineering ◽

Growth Factors ◽

Bone Regeneration ◽

Cell Types ◽

Bone Grafts ◽

Medical Intervention ◽

Scaffold Material ◽

Synthetic Bone ◽

And Function ◽

Synthetic Bone Grafts

Bone is a regenerative organ characterized by self-renewal ability. Indeed, it is a very dynamic tissue subjected to continuous remodeling in order to preserve its structure and function. However, in clinical practice, impaired bone healing can be observed in patients and medical intervention is needed to regenerate the tissue via the use of natural bone grafts or synthetic bone grafts. The main elements required for tissue engineering include cells, growth factors and a scaffold material to support them. Three different materials (metals, ceramics, and polymers) can be used to create a scaffold suitable for bone regeneration. Several cell types have been investigated in combination with biomaterials. In this review, we describe the options available for bone regeneration, focusing on tissue engineering strategies based on the use of different biomaterials combined with cells and growth factors.

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Nanomaterials for Periodontal Tissue Engineering: Chitosan-Based Scaffolds. A Systematic Review

Nanomaterials ◽

10.3390/nano10040605 ◽

2020 ◽

Vol 10 (4) ◽

pp. 605 ◽

Cited By ~ 4

Author(s):

Dorina Lauritano ◽

Luisa Limongelli ◽

Giulia Moreo ◽

Gianfranco Favia ◽

Francesco Carinci

Keyword(s):

Systematic Review ◽

Tissue Engineering ◽

Stem Cells ◽

Alkaline Phosphatase ◽

Growth Factors ◽

Bone Regeneration ◽

Full Text ◽

Periodontal Ligament ◽

Cochrane Library ◽

Periodontal Tissue

Introduction. Several biomaterials are used in periodontal tissue engineering in order to obtain a three-dimensional scaffold, which could enhance the oral bone regeneration. These novel biomaterials, when placed in the affected area, activate a cascade of events, inducing regenerative cellular responses, and replacing the missing tissue. Natural and synthetic polymers can be used alone or in combination with other biomaterials, growth factors, and stem cells. Natural-based polymer chitosan is widely used in periodontal tissue engineering. It presents biodegradability, biocompatibility, and biological renewability properties. It is bacteriostatic and nontoxic and has hemostatic and mucoadhesive capacity. The aim of this systematic review is to obtain an updated overview of the utilization and effectiveness of chitosan-based scaffold (CS-bs) in the alveolar bone regeneration process. Materials and Methods. During database searching (using PubMed, Cochrane Library, and CINAHL), 72 items were found. The title, abstract, and full text of each study were carefully analyzed and only 22 articles were selected. Thirteen articles were excluded based on their title, five after reading the abstract, twenty-six after reading the full text, and six were not considered because of their publication date (prior to 2010). Quality assessment and data extraction were performed in the twelve included randomized controlled trials. Data concerning cell proliferation and viability (CPV), mineralization level (M), and alkaline phosphatase activity (ALPA) were recorded from each article Results. All the included trials tested CS-bs that were combined with other biomaterials (such as hydroxyapatite, alginate, polylactic-co-glycolic acid, polycaprolactone), growth factors (basic fibroblast growth factor, bone morphogenetic protein) and/or stem cells (periodontal ligament stem cells, human jaw bone marrow-derived mesenchymal stem cells). Values about the proliferation of cementoblasts (CB) and periodontal ligament cells (PDLCs), the activity of alkaline phosphatase, and the mineralization level determined by pure chitosan scaffolds resulted in lower than those caused by chitosan-based scaffolds combined with other molecules and biomaterials. Conclusions. A higher periodontal regenerative potential was recorded in the case of CS-based scaffolds combined with other polymeric biomaterials and bioceramics (bio compared to those provided by CS alone. Furthermore, literature demonstrated that the addition of growth factors and stem cells to CS-based scaffolds might improve the biological properties of chitosan.

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Tissue Engineering: Use of Growth Factors in Bone Regeneration

Biomaterials in Regenerative Medicine ◽

10.5772/intechopen.69875 ◽

2018 ◽

Author(s):

Carmen Mortellaro ◽

Massimo Del Fabbro

Keyword(s):

Tissue Engineering ◽

Growth Factors ◽

Bone Regeneration

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Biomaterials for the Delivery of Growth Factors and Other Therapeutic Agents in Tissue Engineering Approaches to Bone Regeneration

Frontiers in Pharmacology ◽

10.3389/fphar.2018.00513 ◽

2018 ◽

Vol 9 ◽

Cited By ~ 43

Author(s):

Christine J. Kowalczewski ◽

Justin M. Saul

Keyword(s):

Tissue Engineering ◽

Growth Factors ◽

Bone Regeneration ◽

Therapeutic Agents

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Advances in Growth Factor Delivery for Bone Tissue Engineering

International Journal of Molecular Sciences ◽

10.3390/ijms22020903 ◽

2021 ◽

Vol 22 (2) ◽

pp. 903

Author(s):

Érica Resende Oliveira ◽

Lei Nie ◽

Daria Podstawczyk ◽

Ahmad Allahbakhsh ◽

Jithendra Ratnayake ◽

...

Keyword(s):

Tissue Engineering ◽

Extracellular Matrix ◽

Growth Factors ◽

Growth Factor ◽

Bone Tissue Engineering ◽

Bone Regeneration ◽

Bone Tissue ◽

Bone Repair ◽

Bone Diseases ◽

Growth Factor Delivery

Shortcomings related to the treatment of bone diseases and consequent tissue regeneration such as transplants have been addressed to some extent by tissue engineering and regenerative medicine. Tissue engineering has promoted structures that can simulate the extracellular matrix and are capable of guiding natural bone repair using signaling molecules to promote osteoinduction and angiogenesis essential in the formation of new bone tissues. Although recent studies on developing novel growth factor delivery systems for bone repair have attracted great attention, taking into account the complexity of the extracellular matrix, scaffolding and growth factors should not be explored independently. Consequently, systems that combine both concepts have great potential to promote the effectiveness of bone regeneration methods. In this review, recent developments in bone regeneration that simultaneously consider scaffolding and growth factors are covered in detail. The main emphasis in this overview is on delivery strategies that employ polymer-based scaffolds for spatiotemporal-controlled delivery of both single and multiple growth factors in bone-regeneration approaches. From clinical applications to creating alternative structural materials, bone tissue engineering has been advancing constantly, and it is relevant to regularly update related topics.

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Decellularized bone extracellular matrix in skeletal tissue engineering

Biochemical Society Transactions ◽

10.1042/bst20190079 ◽

2020 ◽

Vol 48 (3) ◽

pp. 755-764

Author(s):

Benjamin B. Rothrauff ◽

Rocky S. Tuan

Keyword(s):

Tissue Engineering ◽

Bone Regeneration ◽

Tissue Regeneration ◽

Animal Studies ◽

Tumor Resection ◽

Regenerative Capacity ◽

Skeletal Tissue ◽

Large Bone

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.

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