In Situ Tissue Engineering Using Angiogenic Nanoscaffold Enhances Diabetic Wound Healing in db/db Mouse Model

Author(s):  
Swathi Balaji ◽  
Sachin S. Vaikunth ◽  
Jignesh K. Parvadia ◽  
Timothy M. Crombleholme ◽  
Daria A. Narmoneva

Tissue engineering offers an attractive alternative for treatment of chronic nonhealing diabetic ulcers, which account for more than 27% of the $10.9 billion total diabetic health care costs in the US annually [1]. The harsh environment of a diabetic ulcer is characterized by reduced expression of angiogenic factors, insufficient vascularization, excess protease activity, matrix degradation and hyperglycemia-induced cell apoptosis [2]. A major factor contributing to insufficient neovascularization in diabetic nonhealing wounds may be deficiency in the recruitment of endothelial cells (ECs) and endothelial precursor cells (EPCs) to the wound site [3]. Recent studies focusing on altering the wound’s cellular and molecular environment using bone-marrow-derived stem cells, growth factors (delivered either directly or using gene or cell therapy), bioengineered skin constructs, and biological matrices, such as collagen and hyaluronic acid gels had promising wound healing outcomes [4]. These studies suggest that strategies aimed at modifying the extracellular environment of the diabetic wound to enhance cell survival and angiogenesis are promising for development of new therapies for diabetic wound healing.

2019 ◽  
Vol 6 (2) ◽  
pp. 385-393 ◽  
Author(s):  
Zehua Liu ◽  
Yunzhan Li ◽  
Wei Li ◽  
Wenhua Lian ◽  
Marianna Kemell ◽  
...  

A self-regulated dynamic nanohybrid that can sensitively respond to hyperglycemic microenvironment is developed. The nanohybrid with a core/shell structure is produced through a single-step microfluidics nanoprecipitation method, where drugs-loaded porous silicon (PSi) nanoparticles are encapsulated by H2O2 responsive polymeric matrix.


2021 ◽  
Vol 118 ◽  
pp. 111519 ◽  
Author(s):  
Robin Augustine ◽  
Anwarul Hasan ◽  
Yogesh B. Dalvi ◽  
Syed Raza Ur Rehman ◽  
Ruby Varghese ◽  
...  

2014 ◽  
Vol 112 (1) ◽  
pp. 94-99 ◽  
Author(s):  
Dominik Duscher ◽  
Evgenios Neofytou ◽  
Victor W. Wong ◽  
Zeshaan N. Maan ◽  
Robert C. Rennert ◽  
...  

There is a high mortality in patients with diabetes and severe pressure ulcers. For example, chronic pressure sores of the heels often lead to limb loss in diabetic patients. A major factor underlying this is reduced neovascularization caused by impaired activity of the transcription factor hypoxia inducible factor-1 alpha (HIF-1α). In diabetes, HIF-1α function is compromised by a high glucose-induced and reactive oxygen species-mediated modification of its coactivator p300, leading to impaired HIF-1α transactivation. We examined whether local enhancement of HIF-1α activity would improve diabetic wound healing and minimize the severity of diabetic ulcers. To improve HIF-1α activity we designed a transdermal drug delivery system (TDDS) containing the FDA-approved small molecule deferoxamine (DFO), an iron chelator that increases HIF-1α transactivation in diabetes by preventing iron-catalyzed reactive oxygen stress. Applying this TDDS to a pressure-induced ulcer model in diabetic mice, we found that transdermal delivery of DFO significantly improved wound healing. Unexpectedly, prophylactic application of this transdermal delivery system also prevented diabetic ulcer formation. DFO-treated wounds demonstrated increased collagen density, improved neovascularization, and reduction of free radical formation, leading to decreased cell death. These findings suggest that transdermal delivery of DFO provides a targeted means to both prevent ulcer formation and accelerate diabetic wound healing with the potential for rapid clinical translation.


Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
CBS Lau ◽  
VKM Lau ◽  
CL Liu ◽  
PKK Lai ◽  
JCW Tam ◽  
...  

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 634-P
Author(s):  
PIUL S. RABBANI ◽  
JOSHUA A. DAVID ◽  
DARREN L. SULTAN ◽  
ALVARO P. VILLARREAL-PONCE ◽  
JENNIFER KWONG ◽  
...  

Nanomedicine ◽  
2020 ◽  
Vol 15 (23) ◽  
pp. 2241-2253
Author(s):  
Pengju Zhang ◽  
Yuqi Jiang ◽  
Dan Liu ◽  
Yan Liu ◽  
Qinfei Ke ◽  
...  

Aim: To develop an effective strategy for increasing angiogenesis at diabetic wound sites and thereby accelerating wound healing. Materials & methods: A micropatterned nanofibrous scaffold with bioglass nanoparticles encapsulated inside coaxial fibers was prepared by electrospinning. Results: Si ions could be released in a sustained manner from the scaffolds. The hierarchical micro-/nano-structure of the scaffold was found to act as a temporary extracellular matrix to promote endothelial cell adhesion and growth. The scaffold greatly improved angiogenesis and collagen deposition at the wound site, which shortened the healing period of diabetic wounds. Conclusion: This study provides a promising therapeutic option for chronic diabetic wounds with improved angiogenesis.


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