Development of growth factor-incorporating liposomes for integration into scaffolds as a method to improve tissue regeneration

2021 ◽  
Author(s):  
E. Natsaridis ◽  
P. Mouzoura ◽  
F. Gkartziou ◽  
A. Marazioti ◽  
S.G. Antimisiaris
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Tissue Regeneration ◽  
Structural Characteristics ◽  
Drug Carriers ◽  
Growth Factor Delivery ◽  
Liposomal Form ◽  
Liposomal Drug ◽  
Hydrophilic Nature ◽  
Rapid Clearance

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.

scholarly journals PEG grafted chitosan scaffold for dual growth factor delivery for enhanced wound healing

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Amritha Vijayan ◽  
Sabareeswaran A. ◽  
G. S. Vinod Kumar
Keyword(s):  
Wound Healing ◽  
Growth Factors ◽  
Growth Factor ◽  
Treated Group ◽  
Growth Factor Delivery ◽  
Chitosan Scaffold ◽  
Collagen Formation ◽  
Dual Growth Factor Delivery

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.

scholarly journals 3D bioprinting spatiotemporally defined patterns of growth factors to tightly control tissue regeneration

2020 ◽  
Vol 6 (33) ◽  
pp. eabb5093 ◽  
Author(s):  
Fiona E. Freeman ◽  
Pierluca Pitacco ◽  
Lieke H. A. van Dommelen ◽  
Jessica Nulty ◽  
David C. Browe ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Tissue Regeneration ◽  
Point Of Care ◽  
Release Kinetics ◽  
Spatial Gradient ◽  
Heterotopic Bone ◽  
Heterotopic Bone Formation ◽  
Bone Defect Healing

Therapeutic growth factor delivery typically requires supraphysiological dosages, which can cause undesirable off-target effects. The aim of this study was to 3D bioprint implants containing spatiotemporally defined patterns of growth factors optimized for coupled angiogenesis and osteogenesis. Using nanoparticle functionalized bioinks, it was possible to print implants with distinct growth factor patterns and release profiles spanning from days to weeks. The extent of angiogenesis in vivo depended on the spatial presentation of vascular endothelial growth factor (VEGF). Higher levels of vessel invasion were observed in implants containing a spatial gradient of VEGF compared to those homogenously loaded with the same total amount of protein. Printed implants containing a gradient of VEGF, coupled with spatially defined BMP-2 localization and release kinetics, accelerated large bone defect healing with little heterotopic bone formation. This demonstrates the potential of growth factor printing, a putative point of care therapy, for tightly controlled tissue regeneration.

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 ◽  
...  
Keyword(s):  
Growth Factors ◽  
Controlled Release ◽  
Growth Factor ◽  
Half Life ◽  
Growth Factor Delivery ◽  
Short Half Life

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.

scholarly journals Ultrahigh protein adsorption capacity and sustained release of nanocomposite scaffolds: implication for growth factor delivery systems

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
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Sustained Release ◽  
Protein Adsorption ◽  
Adsorption Capacity ◽  
Delivery Systems ◽  
Growth Factor Delivery ◽  
Load Growth ◽  
Nanocomposite Scaffolds

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

Growth factors and myelin regeneration in multiple sclerosis

1997 ◽  
Vol 3 (2) ◽  
pp. 113-120 ◽  
Author(s):  
Henry de F Webster
Keyword(s):  
Multiple Sclerosis ◽  
Growth Factors ◽  
Growth Factor ◽  
Structural Characteristics ◽  
Autoimmune Encephalomyelitis ◽  
Myelin Sheaths ◽  
Igf I ◽  
Lesion Severity ◽  
Experimental Autoimmune

Insulin-like growth factor-I (IGF-I), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF) and ciliary neurotrophic factor (CNTF) are multifunctional growth factors which are found in the CNS. Oligodendroglia are the cells that form and maintain myelin sheaths and many in vitro experiments have shown that these growth factors promote the proliferation, differentiation and survival of cells in the oligodendroglial lineage. Since myelin breakdown is often severe in multiple sclerosis (MS), the possibility of growth factor use in the treatment of MS has been considered and recently, IGF-I treatment has been shown to reduce lesion severity and promote myelin regeneration in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. This review briefly summarizes the structural characteristics of these growth factors and the actions which might help reduce oligodendrocyte-myelin sheath injury in MS and promote myelin regeneration.

Growth-Factor Delivery in Tissue Engineering

MRS Bulletin ◽  
1996 ◽  
Vol 21 (11) ◽  
pp. 62-65 ◽  
Author(s):  
W. Mark Saltzman
Keyword(s):  
Tissue Engineering ◽  
Biological Activity ◽  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
The Body ◽  
Blood Levels ◽  
Growth Factor Delivery ◽  
Angiogenic Growth Factors ◽  
New Methods

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.

scholarly journals Nanofibrous bicomponent scaffolds for the dual delivery of NGF and GDNF: controlled release of growth factors and their biological effects

2021 ◽  
Vol 32 (1) ◽  
Author(s):  
Chaoyu Liu ◽  
Xiaohua Li ◽  
Qilong Zhao ◽  
Yuancai Xie ◽  
Xumei Yao ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Neural Differentiation ◽  
Biological Effects ◽  
In Vitro Release ◽  
Nerve Tissue ◽  
Growth Factor Delivery ◽  
Dual Growth Factor Delivery ◽  
Dual Source

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.

scholarly journals Electrically Stimulated Tunable Drug Delivery From Polypyrrole-Coated Polyvinylidene Fluoride

2021 ◽  
Vol 9 ◽  
Author(s):  
Solaleh Miar ◽  
Joo L. Ong ◽  
Rena Bizios ◽  
Teja Guda
Keyword(s):  
Drug Delivery ◽  
Growth Factors ◽  
Growth Factor ◽  
Drug Release ◽  
Tissue Regeneration ◽  
Polyvinylidene Fluoride ◽  
Drug Loading ◽  
Electrical Stimulus ◽  
Musculoskeletal Tissue ◽  
Stimulus Responsive

Electrical stimulus-responsive drug delivery from conducting polymers such as polypyrrole (PPy) has been limited by lack of versatile polymerization techniques and limitations in drug-loading strategies. In the present study, we report an in-situ chemical polymerization technique for incorporation of biotin, as the doping agent, to establish electrosensitive drug release from PPy-coated substrates. Aligned electrospun polyvinylidene fluoride (PVDF) fibers were used as a substrate for the PPy-coating and basic fibroblast growth factor and nerve growth factor were the model growth factors demonstrated for potential applications in musculoskeletal tissue regeneration. It was observed that 18-h of continuous polymerization produced an optimal coating of PPy on the surface of the PVDF electrospun fibers with significantly increased hydrophilicity and no substantial changes observed in fiber orientation or individual fiber thickness. This PPy-PVDF system was used as the platform for loading the aforementioned growth factors, using streptavidin as the drug-complex carrier. The release profile of incorporated biotinylated growth factors exhibited electrosensitive release behavior while the PPy-PVDF complex proved stable for a period of 14 days and suitable as a stimulus responsive drug delivery depot. Critically, the growth factors retained bioactivity after release. In conclusion, the present study established a systematic methodology to prepare PPy coated systems with electrosensitive drug release capabilities which can potentially be used to encourage targeted tissue regeneration and other biomedical applications.

scholarly journals Effects of Controlled Dual Growth Factor Delivery on Bone Regeneration Following Composite Bone-Muscle Injury

2020 ◽  
Author(s):  
Ramesh Subbiah ◽  
Albert Cheng ◽  
Marissa A. Ruehle ◽  
Marian H. Hettiaratchi ◽  
Luiz E. Bertassoni ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Bone Tissue ◽  
Treatment Strategy ◽  
Growth Factor Delivery ◽  
Treatment Groups ◽  
Vascular Growth ◽  
Injury Model ◽  
Dual Growth Factor Delivery

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.

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