Journal
MOLECULAR PHARMACEUTICS
Volume 9, Issue 1, Pages 48-58Publisher
AMER CHEMICAL SOC
DOI: 10.1021/mp200246b
Keywords
emulsion electrospinning; core-sheath structure; pbFGF polyplex-loaded fibers; diabetic ulcer; skin regeneration
Funding
- National Natural Science Foundation of China [20774075, 51073130]
- National Basic Research Program of China (973 Program) [2012CB933602]
- Fundamental Research Funds for the Central Universities [SWJTU11CX126, SWJTU11ZT10, SWJTU09ZT21]
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Deep or chronic skin wounds are difficult to heal spontaneously due to the lack of scaffold to guide cell growth and reduced levels and activities of endogenous growth factors. Emulsion electrospinning process integrated with DNA condensation techniques indicated potentials to gradually release DNA, but no attempt has been made to clarify the advantages in promoting tissue regeneration and wound recovery. In this study, polyplexes of basic fibroblast growth factor-encoding plasmid (pbFGF) with poly(ethylene imine) were incorporated into electrospun fibers with a core-sheath structure, and poly(ethylene glycol) was included into the fiber sheath to allow a sustained release of pbFGF for 4 weeks. In vitro tests on mouse embryo fibroblasts indicated that pbFGF-loaded fibrous mats enhanced cell proliferation by the autocrine bFGF, and an effective cell transfection proceeded for over 28 days. Skin wounds were created in the dorsal area of diabetic rats for in vivo evaluation of skin regeneration after being covered with pbFGF-loaded fibrous mats. The gradual pbFGF release revealed significantly higher wound recovery rate with improved vascularization, enhanced collagen deposition and maturation, complete re-epithelialization and formation of skin appendages. The above results demonstrate the potential use of pbFGF-loaded electrospun fibrous mats to accelerate the healing of skin ulcers for patients with diabetic mellitus.
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