A break of extracellular matrix (ECM) balance can cause several degenerative changes in soft tissues. To reverse the imbalance fundamentally, a recently developed treatment, gene therapy, came to attention. However, the efficiency of the approach is limited because long‐term localized presence and bioactivity are difficult to achieve. Here, reconstituted lysyl oxidase‐like 1 (LOXL1) plasmids (pLOXL1) are loaded into nanoliposomes by a microfluidic chip, followed by encapsulation into the core layer of core–shell nanofibers by microsol‐electrospinning to achieve local accumulation and biological availability of the constructs and enable rapid ECM response. Results show that the pLOXL1‐Lipo@PLCL‐HA achieves the sustained release of pLOXL1 over a 30‐day period, with its transfection efficiency maintained above 50%. In a rabbit model of abdominal hernia, the long‐term collagen remodeling density is raised by over 90% in the pLOXL1‐Lipo@PLCL‐HA implanted animals compared to the control animals. The expression levels of ECM gene (COL1A1, COL3A1, Elastin, Fubilin5) are significantly increased. Collectively, this study establishes that pLOXL1‐Lipo@PLCL‐HA accelerates local ECM reconstruction via effective and reliable gene delivery as a potential base material of a “patch” for pelvic floor repairment, and identifies the key principles for design of LOXL1‐incorporated scaffolds for ECM regeneration.
Regenerative medicine aims to provide solutions for structural and functional recovery in conditions where organs suffer from varying degrees of diseases or injuries. However, the exogenous inflammation triggered by implanted biomaterials and endogenous inflammation caused by some disease or tissue destruction has not been solved properly yet. Herein, a functional "inner-outer" medicated core-shell electrospun fibrous membrane is fabricated with RGD surface modification for exogenous inflammation suppression and puerarin loading in the core for long-term endogenous inflammation inhibition through microsol electrospinning technique. The "outer" RGD significantly increases biocompatibility of fibrous membrane through promoting cell viability, adhesion, and proliferation while the "inner" puerarin suppresses inflammatory gene expression via sustained drug release in vitro. Moreover, in a rat abdominal wall hernia model, the functional fibrous membrane successfully reduces exogenous and endogenous inflammation response and promotes wound healing through collagen deposition, smooth muscle formation, and vascularization. In summary, the functional "inner-outer" medicated fibrous membrane holds a great potential for clinical treatment of diseases that needs tissue reconstruction structurally and functionally accompanied by immunoregulation.
Early cleavage is a strong indicator of embryo quality, and may be used as an additional criterion in the selection of embryos for transfer to increase pregnancy rate and reduce multiple pregnancy rate.
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