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.

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 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.

Non-mulberry silk fibroin grafted poly(ε-caprolactone) nanofibrous scaffolds mineralized by electrodeposition: an optimal delivery system for growth factors to enhance bone regeneration

RSC Advances ◽  
2016 ◽  
Vol 6 (32) ◽  
pp. 26835-26855 ◽  
Author(s):  
Promita Bhattacharjee ◽  
Deboki Naskar ◽  
Tapas K. Maiti ◽  
Debasis Bhattacharya ◽  
Subhas C. Kundu
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Bone Regeneration ◽  
Silk Fibroin ◽  
Delivery System ◽  
Growth Factor Delivery ◽  
Nanofibrous Scaffolds ◽  
Dual Growth Factor Delivery ◽  
Delivery Medium

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.

scholarly journals Possible mechanism for acceleration of meiotic progression of bovine follicular oocytes by growth factors in vitro

Reproduction ◽  
2002 ◽  
pp. 135-142 ◽  
Author(s):  
M Sakaguchi ◽  
T Dominko ◽  
N Yamauchi ◽  
ML Leibfried-Rutledge ◽  
T Nagai ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Kinase Activity ◽  
Polar Body ◽  
Control Group ◽  
Meiotic Cell ◽  
Treatment Groups ◽  
Igf I ◽  
Polar Body Extrusion

The mechanism for the accelerating effects of epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I) on the meiotic cell cycle of bovine oocytes cultured in vitro was investigated. Cumulus-oocyte complexes (COCs) were obtained from small (< or = 3 mm in diameter), medium (4-6 mm in diameter) or large (7-10 mm in diameter) ovarian follicles and cultured with or without a combination of EGF and IGF-I (growth factors). Growth factors significantly increased the frequency of first polar body extrusion of oocytes derived from small follicles at 16 h of culture (PB16 oocytes; with growth factors: 75%; without growth factors: 55%), but did not increase the frequency in oocytes from medium or large follicles. COCs from small follicles were cultured with individual growth factors and sampled for kinase activity. The frequencies of polar body extrusion in EGF only (67%) and EGF + IGF-I (75%) treatment groups were significantly higher than those in the control (no growth factor) group (49%), but not significantly higher than in the IGF-I only group (63%). The H1 kinase activity at 6-8 h of culture in each group increased significantly from the baseline value at 0 h of culture, and the H1 kinase activities in the EGF only, IGF-I only and EGF + IGF-I treatment groups were significantly higher than those in the control group at 8 h of culture. MAP kinase activity was significantly higher than the baseline value and significantly higher than that in the control group at 6 h of culture in the EGF treatment group only. In conclusion, EGF and IGF-I act on COCs from small follicles to accelerate the meiotic cell cycle of the oocytes. This accelerating effect may be related to increased H1 and MAP kinase activities during the early stages of maturation.

Osteogenic/Angiogenic Dual Growth Factor Delivery Microcapsules for Regeneration of Vascularized Bone Tissue

2015 ◽  
Vol 4 (13) ◽  
pp. 1982-1992 ◽  
Author(s):  
Ramesh Subbiah ◽  
Mintai Peter Hwang ◽  
Se Young Van ◽  
Sun Hee Do ◽  
Hansoo Park ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Tissue ◽  
Growth Factor Delivery ◽  
Dual Growth Factor Delivery ◽  
Vascularized Bone

351 EFFECTS OF FETAL CALF SERUM, GROWTH FACTOR, AND HORMONE SUPPLEMENTATION DURING IN VITRO MATURATION ON PARTHENOGENETIC ACTIVATION AND EMBRYO DEVELOPMENT OF FOLLICULAR RABBIT OOCYTES

2007 ◽  
Vol 19 (1) ◽  
pp. 290
Author(s):  
Z. Polgar ◽  
T. Somfai ◽  
V. Angeli ◽  
X. H. Tang ◽  
W. Ji ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Embryo Development ◽  
In Vitro Maturation ◽  
Polar Body ◽  
Calf Serum ◽  
Complete Medium ◽  
Treatment Groups ◽  
Significant Difference

Improvement of the in vitro maturation (IVM) system for rabbit oocytes could play a role in rabbit biotechnology. Our goal was to improve IVM to have an efficient source of rabbit oocytes for further studies on nuclear transfer. The effects of FCS, growth factors, and hormone supplementation on oocyte maturation, activation, and embryo development rates were evaluated. Rabbit ovaries were transferred from the slaughterhouse to the laboratory in PBS. Oocytes were collected by aspiration and subjected to IVM in 3 types of media based on TCM-199. In one group, growth factors (50 ng mL−1 of insulin-like growth factor-I and 10 ng mL−1 of epidermal growth factor) and hormones (5 IU mL−1 of hCG and 5 IU mL−1 of pregnant mare serum gonadotropin) and BSA were added to the IVM medium (IVM+); in the other groups, IVM medium was supplemented with either 10% (IVM + 10% FCS) or 20% FCS (IVM + 20% FCS). Maturation was assessed by the presence of a polar body after 16 h. Matured oocytes were activated twice by electric stimuli (3 DC pulses, 1.6 kV cm−1, 60 µs) and twice by chemical activation (incubation with 2.5 mM 6-DMAP for 30 min, second time for 2 h) and cultured in vitro in Earle's balanced salt solution complete medium at 38.5°C under 5% CO2 in air. Cleavage rates were recorded 16 h after activation and the blastocyst rates were recorded at Day 5 of in vitro culture. Data were analyzed by ANOVA. Maturation rates did not differ between the treatment groups (Table 1). There was no significant difference in cleavage rates between the IVM+ and the IVM + 10% FCS groups; however, the cleavage rate of the IVM + 20% FCS group was significantly lower compared with the others (Table 1; P &lt; 0.05). Development to the blastocyst did not differ significantly between the treatment groups (Table 1; P &lt; 0.05). The results showed that high (20%) FCS supplementation during IVM had a detrimental effect on oocyte cleavage. Hormonal and growth factor supplementation had no beneficial effects on maturation, activation rates, or blastocyst formation, and in fact were not essential for in vitro embryo production in the rabbit. Table 1.Effect of hormonal and growth factor supplementation on embryo development in rabbit oocytes The project was supported by RABIOTECH OMFB-00330/2004, EU FP6 (MEXT-CT-2003-509582, and 518240), Wellcome Trust (Grant No. 070246), and TET CH-28/04.

scholarly journals Advances in Growth Factor Delivery for Bone Tissue Engineering

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.

scholarly journals Scaffolds for Growth Factor Delivery as Applied to Bone Tissue Engineering

2012 ◽  
Vol 2012 ◽  
pp. 1-25 ◽  
Author(s):  
Keith A. Blackwood ◽  
Nathalie Bock ◽  
Tim R. Dargaville ◽  
Maria Ann Woodruff
Keyword(s):  
Tissue Engineering ◽  
Growth Factors ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Donor Site ◽  
Structural Features ◽  
Donor Site Morbidity ◽  
Tissue Type ◽  
Specific Cell ◽  
Growth Factor Delivery

There remains a substantial shortfall in the treatment of severe skeletal injuries. The current gold standard of autologous bone grafting from the same patient has many undesirable side effects associated such as donor site morbidity. Tissue engineering seeks to offer a solution to this problem. The primary requirements for tissue-engineered scaffolds have already been well established, and many materials, such as polyesters, present themselves as potential candidates for bone defects; they have comparable structural features, but they often lack the required osteoconductivity to promote adequate bone regeneration. By combining these materials with biological growth factors, which promote the infiltration of cells into the scaffold as well as the differentiation into the specific cell and tissue type, it is possible to increase the formation of new bone. However due to the cost and potential complications associated with growth factors, controlling the rate of release is an important design consideration when developing new bone tissue engineering strategies. This paper will cover recent research in the area of encapsulation and release of growth factors within a variety of different polymeric scaffolds.

scholarly journals Microenvironment Influence of a Novel Bioengineered Wound Product, APIS®: A Preliminary In Vitro Analysis of Inflammatory Marker and Growth Factor Secretion

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Isaac Rodriguez ◽  
Tricia Conti ◽  
Nina Bionda
Keyword(s):  
Biological Activity ◽  
Growth Factors ◽  
Growth Factor ◽  
Chronic Wounds ◽  
Inflammatory Marker ◽  
Protein Levels ◽  
Vitro Analysis ◽  
Related Proteins ◽  
Endothelial Growth Factor

Objective. Preliminary biological activity assessment of a novel bioengineered wound product (APIS®, SweetBio, Inc., Memphis, TN, USA), a synthesis of gelatin, Manuka honey, and hydroxyapatite, with in vitro indications to protect, instill balance to, and progress the wound microenvironment. Approach. The biological activity the bioengineered wound product (BWP) elicits on human cells in vitro was assessed by evaluating matrix metalloproteinase- (MMP-) related proteins expressed by macrophages and secretion of growth factors in fibroblasts. Cells were cultured with no treatment, stimulated with lipopolysaccharides (LPS), or seeded directly on the BWP for 24 hours. An additional 72-hour time point for the BWP was assessed to determine if the BWP maintained its activity compared to itself at 24 hours. Cell culture supernatants were assayed to quantify secreted protein levels. Results. MMP-9 secretion from macrophages seeded on the BWP were nondetectable ( P < 0.01 ), while a tissue inhibitor of MMP (TIMP-1) was detected. This decreased the overall MMP-9/TIMP-1 ratio secreted from macrophages seeded on the BWP compared to the controls. Additionally, the secretion of prohealing growth factors such as basic fibroblast growth factor (FGFb) and vascular endothelial growth factor (VEGF) was observed. Conclusion. Results from this preliminary in vitro evaluation suggest that the BWP has the potential to instill balance to the wound microenvironment by reducing the MMP-9/TIMP-1 ratio secretion from macrophages and progress previously stalled chronic wounds towards healing by triggering the release of growth factors from fibroblasts.

scholarly journals Effect of adding growth factors during in vitro maturation on the developmental potentials of ewe oocytes selected by brilliant cresyl blue staining

2021 ◽  
Vol 14 (2) ◽  
pp. 452-456
Author(s):  
Mohamed Fathi ◽  
Amr F. Elkarmoty
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Embryo Development ◽  
In Vitro Maturation ◽  
Blue Staining ◽  
Brilliant Cresyl Blue ◽  
Cresyl Blue ◽  
Nuclear Maturation ◽  
Maturation Medium

Aim: Several factors had been concerned with the developmental competence of the sheep oocyte. This study aims to investigate the effect of adding growth factors (insulin-like growth factor 1 [IGF-1] and epidermal growth factor [EGF]) in the maturation medium of ewe oocytes selected based on brilliant cresyl blue (BCB) screening on in vitro maturation (IVM), fertilization, and pre-implantation embryo development. Materials and Methods: Cumulus-oocyte complexes (COCs) were obtained from the ovaries of slaughtered ewes by either aspiration or slicing techniques. COCs were in vitro matured in a medium containing IGF-1 and EGF (control group). For BCB screening, oocytes were stained and divided into BCB+ oocytes that matured in the same maturation conditions without adding growth factors (Group 2) or in the presence of growth factors (Group 3), and BCB– oocytes that matured in medium without growth factors (Group 4) or with growth factors (Group 5). Results: The supplementation of the maturation medium with growth factors during IVM of (BCB+) oocytes resulted in a significant increase in nuclear maturation rate (90.9%), fertilization rate (75.6%), and embryo developmental rates (60.0%, 46.7%, and 33.3% for cleavage, morula, and blastocyst, respectively). Conclusion: Culturing BCB+ oocytes in a maturation medium containing both EGF and IGF-1 showed a significant improvement in nuclear maturation, fertilization, and pre-implantation embryo development in vitro.

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