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 ◽  
...  
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.


2017 ◽  
Vol 35 (5) ◽  
pp. 1086-1095 ◽  
Author(s):  
Farzana Sharmin ◽  
Casey McDermott ◽  
Jay Lieberman ◽  
Archana Sanjay ◽  
Yusuf Khan

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.


2013 ◽  
Vol 19 (17-18) ◽  
pp. 2076-2086 ◽  
Author(s):  
Daphne L. Hutton ◽  
Erika M. Moore ◽  
Jeffrey M. Gimble ◽  
Warren L. Grayson

2016 ◽  
Vol 24 (4) ◽  
pp. 385-391 ◽  
Author(s):  
Min Suk Lee ◽  
Sajeesh Kumar ◽  
Wan-Geun La ◽  
Jun Sung Oh ◽  
Hae In Choi ◽  
...  

RSC Advances ◽  
2018 ◽  
Vol 8 (30) ◽  
pp. 16503-16512 ◽  
Author(s):  
Chun Xu ◽  
Jia Xu ◽  
Lan Xiao ◽  
Zhihao Li ◽  
Yin Xiao ◽  
...  

Microsphere based drug delivery systems show great advantages for tissue engineering.


Biomaterials ◽  
2014 ◽  
Vol 35 (31) ◽  
pp. 8829-8839 ◽  
Author(s):  
Steven Lu ◽  
Johnny Lam ◽  
Jordan E. Trachtenberg ◽  
Esther J. Lee ◽  
Hajar Seyednejad ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document