Rational design and protein engineering of growth factors for regenerative medicine and tissue engineering

2009 ◽  
Vol 37 (4) ◽  
pp. 717-721 ◽  
Author(s):  
Andrew J. Moss ◽  
Shikha Sharma ◽  
Nicholas P.J. Brindle
Keyword(s):  
Tissue Engineering ◽  
Growth Factors ◽  
Protein Engineering ◽  
Rational Design ◽  
Receptor Activation ◽  
Natural Growth ◽  
Combinatorial Protein Engineering ◽  
Sites Of Action ◽  
Synthetic Growth

Growth factors provide key instructive cues for tissue formation and repair. However, many natural growth factors are limited in their usefulness for tissue engineering and regenerative applications by their poor retention at desired sites of action, short half-lives in vivo, pleiotropic actions and other features. In the present article, we review approaches to rational design of synthetic growth factors based on mechanisms of receptor activation. Such synthetic molecules can function as simplified ligands with potentially tunable specificity and action. Rational and combinatorial protein engineering techniques allow introduction of additional features into these synthetic growth molecules, as well as natural growth factors, which significantly enhance their therapeutic utility.

TRENDS AND CHALLENGES OF CARTILAGE TISSUE ENGINEERING

2009 ◽  
Vol 21 (03) ◽  
pp. 149-155 ◽  
Author(s):  
Hsu-Wei Fang
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Growth Factors ◽  
Bone Cells ◽  
Cartilage Tissue Engineering ◽  
Bioactive Molecules ◽  
In Vivo Studies ◽  
Cartilage Tissue

Cartilage injuries may be caused by trauma, biomechanical imbalance, or degenerative changes of joint. Unfortunately, cartilage has limited capability to spontaneous repair once damaged and may lead to progressive damage and degeneration. Cartilage tissue-engineering techniques have emerged as the potential clinical strategies. An ideal tissue-engineering approach to cartilage repair should offer good integration into both the host cartilage and the subchondral bone. Cells, scaffolds, and growth factors make up the tissue engineering triad. One of the major challenges for cartilage tissue engineering is cell source and cell numbers. Due to the limitations of proliferation for mature chondrocytes, current studies have alternated to use stem cells as a potential source. In the recent years, a lot of novel biomaterials has been continuously developed and investigated in various in vitro and in vivo studies for cartilage tissue engineering. Moreover, stimulatory factors such as bioactive molecules have been explored to induce or enhance cartilage formation. Growth factors and other additives could be added into culture media in vitro, transferred into cells, or incorporated into scaffolds for in vivo delivery to promote cellular differentiation and tissue regeneration.Based on the current development of cartilage tissue engineering, there exist challenges to overcome. How to manipulate the interactions between cells, scaffold, and signals to achieve the moderation of implanted composite differentiate into moderate stem cells to differentiate into hyaline cartilage to perform the optimum physiological and biomechanical functions without negative side effects remains the target to pursue.

Collagen fibrous scaffolds for sustained delivery of growth factors for meniscal tissue engineering

Nanomedicine ◽  
2022 ◽  
Author(s):  
Jihye Baek ◽  
Kwang Il Lee ◽  
Ho Jong Ra ◽  
Martin K Lotz ◽  
Darryl D D'Lima
Keyword(s):  
Tissue Engineering ◽  
Growth Factors ◽  
Sustained Release ◽  
Ex Vivo ◽  
Synovial Cell ◽  
Growth Factor Delivery ◽  
Meniscal Tissue ◽  
A Cell

Aim: To mimic the ultrastructural morphology of the meniscus with nanofiber scaffolds coupled with controlled growth factor delivery to modulate cellular performance for tissue engineering of menisci. Methods: The authors functionalized collagen nanofibers by conjugating heparin to the following growth factors for sustained release: PDGF-BB, TGF-β1 and CTGF. Results: Incorporating growth factors increased human meniscal and synovial cell viability, proliferation and infiltration in vitro, ex vivo and in vivo; upregulated key genes involved in meniscal extracellular matrix synthesis; and enhanced generation of meniscus-like tissue. Conclusion: The authors' results indicate that functionalizing collagen nanofibers can create a cell-favorable micro- and nanoenvironment and can serve as a system for sustained release of bioactive factors.

scholarly journals Craniofacial Bone Tissue Engineering: Current Approaches and Potential Therapy

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2993
Author(s):  
Arbi Aghali
Keyword(s):  
Tissue Engineering ◽  
Growth Factors ◽  
Bone Tissue ◽  
Stromal Cells ◽  
Critical Size ◽  
Tumor Resection ◽  
Bone Morphogenetic Protein 2 ◽  
Craniofacial Bone

Craniofacial bone defects can result from various disorders, including congenital malformations, tumor resection, infection, severe trauma, and accidents. Successfully regenerating cranial defects is an integral step to restore craniofacial function. However, challenges managing and controlling new bone tissue formation remain. Current advances in tissue engineering and regenerative medicine use innovative techniques to address these challenges. The use of biomaterials, stromal cells, and growth factors have demonstrated promising outcomes in vitro and in vivo. Natural and synthetic bone grafts combined with Mesenchymal Stromal Cells (MSCs) and growth factors have shown encouraging results in regenerating critical-size cranial defects. One of prevalent growth factors is Bone Morphogenetic Protein-2 (BMP-2). BMP-2 is defined as a gold standard growth factor that enhances new bone formation in vitro and in vivo. Recently, emerging evidence suggested that Megakaryocytes (MKs), induced by Thrombopoietin (TPO), show an increase in osteoblast proliferation in vitro and bone mass in vivo. Furthermore, a co-culture study shows mature MKs enhance MSC survival rate while maintaining their phenotype. Therefore, MKs can provide an insight as a potential therapy offering a safe and effective approach to regenerating critical-size cranial defects.

scholarly journals Biological perspectives and current biofabrication strategies in osteochondral tissue engineering

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Cian Vyas ◽  
Hussein Mishbak ◽  
Glen Cooper ◽  
Chris Peach ◽  
Ruben F. Pereira ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Rational Design ◽  
Therapeutic Interventions ◽  
Ageing Population ◽  
Clinical Practices ◽  
Tissue Constructs ◽  
Systems Research ◽  
Starting Point ◽  
Osteochondral Tissue

Abstract Articular cartilage and the underlying subchondral bone are crucial in human movement and when damaged through disease or trauma impacts severely on quality of life. Cartilage has a limited regenerative capacity due to its avascular composition and current therapeutic interventions have limited efficacy. With a rapidly ageing population globally, the numbers of patients requiring therapy for osteochondral disorders is rising, leading to increasing pressures on healthcare systems. Research into novel therapies using tissue engineering has become a priority. However, rational design of biomimetic and clinically effective tissue constructs requires basic understanding of osteochondral biological composition, structure, and mechanical properties. Furthermore, consideration of material design, scaffold architecture, and biofabrication strategies, is needed to assist in the development of tissue engineering therapies enabling successful translation into the clinical arena. This review provides a starting point for any researcher investigating tissue engineering for osteochondral applications. An overview of biological properties of osteochondral tissue, current clinical practices, the role of tissue engineering and biofabrication, and key challenges associated with new treatments is provided. Developing precisely engineered tissue constructs with mechanical and phenotypic stability is the goal. Future work should focus on multi-stimulatory environments, long-term studies to determine phenotypic alterations and tissue formation, and the development of novel bioreactor systems that can more accurately resemble the in vivo environment.

scholarly journals Research Advances in Tissue Engineering Materials for Sustained Release of Growth Factors

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Hai-yang Zhao ◽  
Jiang Wu ◽  
Jing-jing Zhu ◽  
Ze-cong Xiao ◽  
Chao-chao He ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Growth Factors ◽  
Sustained Release ◽  
Enzymatic Degradation ◽  
Bone Repair ◽  
Sustained Delivery ◽  
System Disease ◽  
Free Growth ◽  
Intense Research

Growth factors are a class of cytokines that stimulate cell growth and are widely used in clinical practice, such as wound healing, revascularization, bone repair, and nervous system disease. However, free growth factors have a short half-life and are instablein vivo. Therefore, the search of excellent carriers to enhance sustained release of growth factorsin vivohas become an area of intense research interest. The development of controlled-release systems that protect the recombinant growth factors from enzymatic degradation and provide sustained delivery at the injury site during healing should enhance the growth factor’s application in tissue regeneration. Thus, this study reviews current research on commonly used carriers for sustained release of growth factors and their sustained release effects for preservation of their bioactivity and their accomplishment in tissue engineering approaches.

scholarly journals Nanotopography in directing osteogenic differentiation of mesenchymal stem cells: potency and future perspective

2021 ◽  
Author(s):  
Anggraini Barlian ◽  
Katherine Vanya
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factors ◽  
Osteogenic Differentiation ◽  
Future Perspective ◽  
Osteogenic Markers

Severe bone injuries can result in disabilities and thus affect a person's quality of life. Mesenchymal stem cells (MSCs) can be an alternative for bone healing by growing them on nanopatterned substrates that provide mechanical signals for differentiation. This review aims to highlight the role of nanopatterns in directing or inducing MSC osteogenic differentiation, especially in bone tissue engineering. Nanopatterns can upregulate the expression of osteogenic markers, which indicates a faster differentiation process. Combined with growth factors, nanopatterns can further upregulate osteogenic markers, but with fewer growth factors needed, thereby reducing the risks and costs involved. Nanopatterns can be applied in scaffolds for tissue engineering for their lasting effects, even in vivo, thus having great potential for future bone treatment.

scholarly journals Application of Tissue Engineering in Tooth: A Review on Recent Trends and Advances

2020 ◽  
Vol 213 ◽  
pp. 03028
Author(s):  
Zeyu Chen
Keyword(s):  
Tissue Engineering ◽  
Growth Factors ◽  
Human Health ◽  
Tooth Loss ◽  
Dental Tissue ◽  
Functional Tooth ◽  
Recent Trends ◽  
Dental Tissue Engineering ◽  
Missing Tooth

Tooth loss has endangered human health for thousands of years, and people can apply dentures or dental implants to restore tooth loss today. Tissue engineering provides a novel way to regenerate a new functional tooth in vivo or vitro to help patients regain masticatory function and appearance. In this summarize review, we will discuss some promising seed cells in dental tissue engineering, the scaffolds that can be used to regenerate teeth, and some growth factors which can promote the development of tooth. Although significant progresses have been made nowadays, some challenges still remain. Hence, tissue engineering could be a choice to replace missing tooth in the future when the obstacles are solved.

Growth Factors and Scaffold Composition Influence Properties of Tissue Engineered Human Septal Cartilage Implants in a Murine Model

2008 ◽  
Vol 21 (4) ◽  
pp. 807-816 ◽  
Author(s):  
D. Skodacek ◽  
S. Brandau ◽  
T. Deutschle ◽  
S. Lang ◽  
N. Rotter
Keyword(s):  
Tissue Engineering ◽  
Growth Factors ◽  
Ex Vivo ◽  
Septal Cartilage ◽  
Hydroxyproline Content ◽  
Wet Weight ◽  
Cell Carriers ◽  
Scaffold Properties

Several surgical disciplines apply cartilage grafts for reconstructive purposes and have to overcome the scarcity of donor sites for this unique tissue. Employing the techniques of tissue engineering, cartilage might be generated in reasonable amounts for clinical purposes. Application of growth factors together with biochemical and biomechanical scaffold properties influence the process of ex vivo transplant production. The aims of this study are: 1) to investigate the influence of IGF-1 and TGFβ-2 on tissue engineered human septal cartilage in vitro and in vivo after transplantation in nude mice; 2) to analyse the effect of the polydioxanone (PDS) content of the biodegradable Ethisorb E210™ scaffold on the properties of the implanted constructs. Cells were three-dimensionally cultured on biodegradable Ethisorb E210™ (PGA-PLA-copolymer fleeces with polydioxanone (PDS) adhesions), or on E210™ scaffolds with a reduced polydioxanone content. Wet weight (ww), GAG-, and hydroxyprolin-content, as well as the cellularity of the neocartilage constructs were quantitatively evaluated. Additionally, the in vivo resorption of the two types of cell carriers was monitored. Addition of growth factors clearly increased the wet weight of the in vitro cultured constructs before transplantation. After transplantation, high PDS content improved the in vivo stability and macroscopic morphometric appearance of the tissue engineered specimens and led to enhanced deposition of glycosaminoglycans in transplanted constructs. Hydroxyproline content of the implants was not affected by either growth factors or PDS content. These data suggest a role for IGF-1 and TGFß-2 in preparative in vitro culture of chondrocytes before implantation, while PDS content of the scaffold is important for in vivo properties of the implanted material.

scholarly journals DNA binding triggers tetramerization of the glucocorticoid receptor in live cells

2016 ◽  
Vol 113 (29) ◽  
pp. 8236-8241 ◽  
Author(s):  
Diego M. Presman ◽  
Sourav Ganguly ◽  
R. Louis Schiltz ◽  
Thomas A. Johnson ◽  
Tatiana S. Karpova ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Glucocorticoid Receptor ◽  
Rational Design ◽  
Quaternary Structure ◽  
Imaging Techniques ◽  
Steroid Receptor ◽  
Receptor Activation ◽  
Live Cells

Transcription factors dynamically bind to chromatin and are essential for the regulation of genes. Although a large percentage of these proteins appear to self-associate to form dimers or higher order oligomers, the stoichiometry of DNA-bound transcription factors has been poorly characterized in vivo. The glucocorticoid receptor (GR) is a ligand-regulated transcription factor widely believed to act as a dimer or a monomer. Using a unique set of imaging techniques coupled with a cell line containing an array of DNA binding elements, we show that GR is predominantly a tetramer when bound to its target DNA. We find that DNA binding triggers an interdomain allosteric regulation within the GR, leading to tetramerization. We therefore propose that dynamic changes in GR stoichiometry represent a previously unidentified level of regulation in steroid receptor activation. Quaternary structure analysis of other members of the steroid receptor family (estrogen, androgen, and progesterone receptors) reveals variation in oligomerization states among this family of transcription factors. Because GR’s oligomerization state has been implicated in therapy outcome, our findings open new doors to the rational design of novel GR ligands and redefine the quaternary structure of steroid receptors.

Incorporation of nanoparticles into transplantable decellularized matrices: Applications and challenges

2018 ◽  
Vol 41 (8) ◽  
pp. 421-430 ◽  
Author(s):  
Tarek M Saleh ◽  
Ebtehal A Ahmed ◽  
Lina Yu ◽  
Ho-Hyun Kwak ◽  
Kamal H Hussein ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Biological Activity ◽  
Growth Factors ◽  
Stem Cell Niche ◽  
Three Dimensional ◽  
High Biological Activity ◽  
Ability To Regenerate ◽  
Cell Niche ◽  
Critical Components

Decellularization of tissues can significantly improve regenerative medicine and tissue engineering by producing natural, less immunogenic, three-dimensional, acellular matrices with high biological activity for transplantation. Decellularized matrices retain specific critical components of native tissues such as stem cell niche, various growth factors, and the ability to regenerate in vivo. However, recellularization and functionalization of these matrices remain limited, highlighting the need to improve the characteristics of decellularized matrices. Incorporating nanoparticles into decellularized tissues can overcome these limitations because nanoparticles possess unique properties such as multifunctionality and can modify the surface of decellularized matrices with additional growth factors, which can be loaded onto the nanoparticles. Therefore, in this minireview, we highlight the various approaches used to improve decellularized matrices with incorporation of nanoparticles and the challenges present in these applications.

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