scholarly journals Biomimetic proteoglycan nanoparticles for growth factor immobilization and delivery

2020 ◽  
Vol 8 (4) ◽  
pp. 1127-1136 ◽  
Author(s):  
Nooshin Zandi ◽  
Ebrahim Mostafavi ◽  
Mohammad Ali Shokrgozar ◽  
Elnaz Tamjid ◽  
Thomas J. Webster ◽  
...  

Growth factor delivery is often challenging due to their short half-life, low stability, and rapid deactivation. Here, we engineered novel biomimetic proteoglycan nanocarriers for the immobilization and controlled release of growth factors.

Author(s):  
E. Natsaridis ◽  
P. Mouzoura ◽  
F. Gkartziou ◽  
A. Marazioti ◽  
S.G. Antimisiaris

This review is an update about the efforts to develop liposomal carriers for growth factor delivery. It is well known that growth factors have the potential to enhance/accelerate tissue regeneration, however their poor stability which results in rapid loss of their activity, together with their rapid clearance from defected tissues (when applied as free molecules) is a serious drawback for their use; their highly hydrophilic nature and low capability to permeate through biological barriers (cell membranes) are additional factors that limit their applicability. In the last years, the advantages of liposomal drug delivery systems have motivated efforts to deliver growth factors (GFs) in liposomal form. Herein, after briefly introducing the basic structural characteristics of liposome types and their advantages when used as drug carriers, as well as the basic problems encountered when GFs are applied for tissue regeneration, we focus on recent reports about development and potential regenerative effects of liposomal GFs, towards defects of various tissues. The methodologies used for incorporation, attachment or immobilization of liposomal GFs in order to sustain their retention at the defected tissues, are highlighted as well.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Amritha Vijayan ◽  
Sabareeswaran A. ◽  
G. S. Vinod Kumar

AbstractApplication of growth factors at wound site has improved the efficiency and quality of healing. Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) induce proliferation of various cells in wound healing. Delivery of growth factor from controlled release systems protect it from degradation and also result in sustained delivery of it at the site of injury. The goal of the study was to develop a Polyethylene glycol (PEG) cross-linked cotton-like chitosan scaffold (CS-PEG-H) by freeze-drying method and chemically conjugate heparin to the scaffold to which the growth factors can be electrostatically bound and evaluate its wound healing properties in vitro and in vivo. The growth factor containing scaffolds induced increased proliferation of HaCaT cells, increased neovascularization and collagen formation seen by H and E and Masson’s trichrome staining. Immunohistochemistry was performed using the Ki67 marker which increased proliferation of cells in growth factor containing scaffold treated group. Frequent dressing changes are a major deterrent to proper wound healing. Our system was found to release both VEGF and bFGF in a continuous manner and attained stability after 7 days. Thus our system can maintain therapeutic levels of growth factor at the wound bed thereby avoiding the need for daily applications and frequent dressing changes. Thus, it can be a promising candidate for wound healing.


RSC Advances ◽  
2017 ◽  
Vol 7 (27) ◽  
pp. 16453-16459 ◽  
Author(s):  
Ji-Young Yoon ◽  
Jung-Ju Kim ◽  
Ahmed El-Fiqi ◽  
Jun-Hyeog Jang ◽  
Hae-Won Kim

Nanocomposite scaffolds that can load growth factors effectively and release them sustainably are developed for the regeneration of tissues.


MRS Bulletin ◽  
1996 ◽  
Vol 21 (11) ◽  
pp. 62-65 ◽  
Author(s):  
W. Mark Saltzman

Soluble signaling proteins called growth factors execute critical functions during the formation of specialized tissues throughout the developing embryo. When growth factors are provided to adult animals, they often encourage regeneration or repair of organs damaged by disease or trauma: Basic fibroblast growth factor (bFGF) and transforming growth factor ß1 (TGF-ß1) encourage wound healing hematopoetic growth factors stimulate the production of blood cells, bone morphogenetic proteins (BMPs) induce bone formation, nerve growth factor (NGF) enhances the survival of degenerating cholinergic neurons, and angiogenic growth factors activate new blood-vessel growth. Our understanding of the role of growth factors in development and regeneration should continue to expand dramatically over the next decade, inasmuch as new molecules (and new activities for known molecules) are appearing at a rapid rate.Protein growth factors may be useful in augmenting the new approaches for tissue engineering. Modern biotechnology permits the large-scale manufacture of highly purified proteins so that large quantities can be produced for use in humans. However proteins are often exceedingly difficult to administer, particularly if sustained levels are required. Most protein growth factors have short half-lives after intravenous injection, with their biological activity lasting only a few minutes in the circulation, so that injection must be repeated frequently to obtain sustained blood levels (Table I). Since these molecules are large, they penetrate tissue barriers, such as the capillary wall, very slowly. In addition, growth factors are extremely potent, often possessing biological activity at a number of tissue sites throughout the body. Therefore systemic administration can lead to toxicity. In view of these difficulties, new methods for growth-factor delivery are needed. The most promising new methods involve polymers, which can be engineered to provide precisely controlled, prolonged growth-factor delivery at a localized site.


Author(s):  
Chaoyu Liu ◽  
Xiaohua Li ◽  
Qilong Zhao ◽  
Yuancai Xie ◽  
Xumei Yao ◽  
...  

AbstractElectrospun fibrous scaffolds capable of providing dual growth factor delivery in a controlled manner have distinctive advantages for tissue engineering. In this study, we have investigated the formation, structure, and characteristics/properties of fibrous bicomponent scaffolds for the dual delivery of glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) for peripheral nerve tissue regeneration. GDNF and NGF were incorporated into core-shell structured poly(lactic-co-glycolic acid) (PLGA) and poly (d,l-lactic acid) (PDLLA) nanofibers, respectively, through emulsion electrospinning. Using dual-source dual-power electrospinning, bicomponent scaffolds composed of GDNF/PLGA fibers and NGF/PDLLA fibers with different fiber component ratios were produced. The structure, properties, and in vitro release behavior of mono- and bicomponent scaffolds were systematically investigated. Concurrent and sustained release of GDNF and NGF from bicomponent scaffolds was achieved and their release profiles could be tuned. In vitro biological investigations were conducted. Rat pheochromocytoma cells were found to attach, spread, and proliferate on all scaffolds. The release of growth factors from scaffolds could induce much improved neurite outgrowth and neural differentiation. GDNF and NGF released from GDNF/PLGA scaffolds and NGF/PDLLA scaffolds, respectively, could induce dose-dependent neural differentiation separately. GDNF and NGF released from bicomponent scaffolds exerted a synergistic effect on promoting neural differentiation.


2020 ◽  
Author(s):  
Ramesh Subbiah ◽  
Albert Cheng ◽  
Marissa A. Ruehle ◽  
Marian H. Hettiaratchi ◽  
Luiz E. Bertassoni ◽  
...  

AbstractThe objective of this study was to investigate the controlled release of two growth factors (BMP-2 and VEGF) as a treatment strategy for clinically challenging composite injuries, consisting of a segmental bone defect and volumetric muscle loss. This is the first investigation of dual growth factor delivery in a composite injury model using an injectable smart delivery system consisting of heparin microparticles and alginate gel. The loading efficiency of growth factors into these biomaterials was found to be >90%, revealing a strong affinity of VEGF and BMP-2 to heparin and alginate. The system could achieve simultaneous or sequential release of VEGF and BMP-2 by varying the loading strategy. Single growth factor delivery (VEGF or BMP-2 alone) significantly enhanced vascular growth in vitro. However, no synergistic effect was observed for dual growth factor (BMP-2 + VEGF) delivery. Effective bone healing was achieved in all treatment groups (BMP-2, simultaneous or sequential delivery of BMP-2 and VEGF) in the composite injury model. The mechanics of the regenerated bone reached a maximum strength of ∼52% of intact bone with sequential delivery of VEGF and BMP-2. Overall, simultaneous or sequential co-delivery of low-dose BMP-2 and VEGF failed to fully restore the mechanics of bone in this injury model. Given the severity of the composite injury, VEGF alone may not be sufficient to establish mature and stable blood vessels when compared with previous studies co-delivering BMP-2+VEGF enhanced bone tissue regeneration. Hence, future studies are warranted to develop an alternative treatment strategy focusing on better control over growth factor dose, spatiotemporal delivery, and additional growth factors to regenerate fully functional bone tissue.HighlightsWe developed a smart growth factor delivery system using heparin microparticles and alginate that facilitates tunable delivery of VEGF and BMP-2 in a simultaneous or sequential manner by merely varying the loading strategy.In vitro, both VEGF and BMP-2 alone promoted vascular growth; however, VEGF was significantly more potent, and there was no detectable benefit of co-delivery.In vivo, both BMP-2 alone and co-delivery of VEGF and BMP-2 promoted bone formation in the challenging bone/muscle polytrauma model; however, none of the treatment groups restored biomechanical properties to that of uninjured bone.


2005 ◽  
Vol 288-289 ◽  
pp. 133-138
Author(s):  
Makoto Ozeki ◽  
Yasuhiko Tabata

This study is an investigation to evaluate how the controlled release of different growth factors affects the hair follicle growth of mice in the second anagen stage of hair cycle. For the controlled release of basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF), they were incorporating into biodegradable gelatin hydrogels, while a biodegradable collagen hydrogel was used for incorporation of vascular endothelial growth factor (VEGF). After subcutaneous implantation of the different hydrogels incorporating each growth factor or injection of phosphate buffered saline (PBS) containing the same dose of growth factor into the back of mice, the hair follicle growth was evaluated photometrically and histologically based on four parameters: the skin color of reverse side of the implanted or injected site, the number of vessels newly formed, the area occupied by hair follicle tissue, and the hair length. The area in close proximity to the implanted site of hydrogels incorporating growth factor was still dark in color 10 days after application. The hydrogel incorporating any type of growth factor enabled the hair follicles to increase the size, leading significantly enhanced area occupied by hair follicles per unit area of tissue. Implantation of the hydrogels incorporating growth factor increased significantly the number of blood vessels newly formed. Moreover, the length of hair shaft was elongated by the hydrogel incorporating growth factor to a significantly higher extent than the corresponding growth factor. Neither empty gelatin nor collagen hydrogels affected the hair follicle growth. These results indicate that the hydrogel incorporating growth factor induced the anagen-preservable activity. We conclude that the controlled release enabled growth factors to positively act on the hair growth cycle of mice, irrespective of the factor type.


RSC Advances ◽  
2016 ◽  
Vol 6 (32) ◽  
pp. 26835-26855 ◽  
Author(s):  
Promita Bhattacharjee ◽  
Deboki Naskar ◽  
Tapas K. Maiti ◽  
Debasis Bhattacharya ◽  
Subhas C. Kundu

Nanofibrous PCL matrix with non-mulberry silk fibroin grafting and electrodeposited nHAp was used successfully as dual growth factor delivery medium for in vitro osteogenesis.


2010 ◽  
Vol 8 (55) ◽  
pp. 153-170 ◽  
Author(s):  
Kangwon Lee ◽  
Eduardo A. Silva ◽  
David J. Mooney

The identification and production of recombinant morphogens and growth factors that play key roles in tissue regeneration have generated much enthusiasm and numerous clinical trials, but the results of many of these trials have been largely disappointing. Interestingly, the trials that have shown benefit all contain a common denominator, the presence of a material carrier, suggesting strongly that spatio-temporal control over the location and bioactivity of factors after introduction into the body is crucial to achieve tangible therapeutic effect. Sophisticated materials systems that regulate the biological presentation of growth factors represent an attractive new generation of therapeutic agents for the treatment of a wide variety of diseases. This review provides an overview of growth factor delivery in tissue engineering. Certain fundamental issues and design strategies relevant to the material carriers that are being actively pursued to address specific technical objectives are discussed. Recent progress highlights the importance of materials science and engineering in growth factor delivery approaches to regenerative medicine.


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