Bioactive substances such as probiotics are becoming
a research
hotspot in the field of tissue regeneration due to their excellent
regulatory functions. Here, we proposed to load Lactobacillus
casei onto a bilayer silk fibroin/sodium alginate
(SF/SA) scaffold to endow the scaffold with both antibacterial and
regenerative properties. The performance of the scaffold was characterized
systemically. The L. casei-loaded scaffolds
(L-SF/SA) bring in lactic acid, which has antibacterial and wound
healing properties. In vitro, the cell-free supernatant
(CFS) of L. casei inhibited the transformation
of fibroblasts to myofibroblasts and relieved the endoplasmic reticulum
stress (ERS). In vivo, L-SF/SA accelerated the healing
of infected wounds in SD rats. The L-SF/SA reduced the bacterial load,
induced M2 polarization of macrophages, increased angiogenesis, regulated
collagen ratio, and alleviated the ERS, thereby promoting scarless
wound healing and increasing hair follicle regeneration. Therefore,
probiotic-functionalized silk fibroin/alginate scaffolds showed potential
in the infected wound healing.
Efficient local delivery of mesenchymal stem cells (MSCs)
is a
decisive factor for their application in regeneration processes. Here,
we prepared a biomimetic bilayer silk fibroin/sodium alginate (SF/SA)
scaffold to deliver human umbilical mesenchymal stem cells (hUC-MSCs)
for wound healing. An SA membrane was prepared by the casting method
on the upper layer of the scaffold to simulate the dense epidermal
structure. On the lower layer, porous materials simulating the loose
structure of the dermis were formed by the freeze-drying method. In vitro, the scaffold was proven to have a high-density
pore structure, good swelling property, and suitable degradation rate.
The hUC-MSCs could survive on the scaffold for up to 14 days and maintain
cell stemness for at least 7 days. In vivo, SF/SA
scaffolds loaded with hUC-MSCs (M-SF/SA) were applied to full-thickness
defect wounds and compared with the local injection of hUC-MSCs. The
M-SF/SA group showed excellent therapeutic efficacy, characterized
by induction of macrophage polarization, regulation of TGF-β
expression and collagen components, and enhancement of vascular regeneration,
thereby preventing scar formation and promoting hair follicle regeneration.
Furthermore, the expression of endoplasmic reticulum stress markers
IRE1, XBP1, and CHOP was inhibited significantly in M-SF/SA treatment.
In conclusion, the bilayer SF/SA scaffold is an ideal delivery platform
for hUC-MSCs, and the M-SF/SA system could locally promote scarless
skin healing and hair follicle regeneration by alleviating the IRE1/XBP1
signal pathway.
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