Severe intrauterine adhesions (IUAs), characterized by inadequate endometrial repair and fibrosis, can lead to infertility. Stem cell-based therapies, which deliver mesenchymal stem cells (MSCs) to the wound site, hold a considerable promise for endometrium regeneration. However, some notable hurdles, such as stemness loss, immunogenicity, low retention and survival rate, limit their clinical application. Evidence shows a strategy of mobilizing endogenous MSCs recruitment can overcome the traditional limitations of exogenous stem cell-based therapies. Here, an acellular biomaterial named stromal derived factor-1 alpha (SDF-1đ¶)/E7-modified collagen scaffold (CES) is explored. CES based on harnessing the innate regenerative potential of the body enables near-complete endometrium regeneration and fertility restoration both in a rat endometrium acute damage model and a rat IUA model. Mechanistically, the CES implantation promotes endogenous MSCs recruitment via a macrophage-coordinated strategy; then the homing MSCs exert the function of immunomodulation and altered local microenvironments toward regeneration. To conclude, CES, which can harness endogenous MSCs and overcome the traditional limitations of cell-based therapies, can serve as a clinically feasible and cell-free strategy with high therapeutic efficiency for IUA treatment.
Stimuli-responsive biomaterials supply a promising solution to adapt to the complex physiological environment for different biomedical applications. In this study, a dynamic UV-triggered pH-responsive biosurface was constructed on titania nanotubes (TNTs) by loading photoacid generators, diphenyliodonium chloride, into the nanotubes, and grafting 2,3-dimethyl maleic anhydride (DMMA)-modified hyperbranched poly(L-lysine) (HBPLL) onto the surface. The local acidity was dramatically enhanced by UV irradiation for only 30 s, leading to the dissociation of DMMA and thereby the transformation of surface chemistry from negatively charged caboxyl groups to positively charged amino groups. The TNTsâHBPLLâDMMA substrate could better promote proliferation and spreading of rat bone mesenchymal stem cells (rBMSCs) after UV irradiation. The osteogenic differentiation of rBMSCs was enhanced because of the charge reversal in combination with the titania-based substrates.
Mesenchymal stem cells (MSCs) have drawn great attention in clinical applications due to the selfârenewal ability, multiâdifferentiation potential, and low immunogenicity. However, there are challenges in the ex vivo expansion of MSCs, including low efficiency, stemness loss, and safety. Therefore, it is crucial to construct a substrate that can show an alterable affinity to MSCs, and induce efficient cell expansion with minimal stemness loss. In this study, EPLQLKM (E7)âmodified substrates with tunable E7 densities are fabricated on PEGylated substrates. The PEG layer with an average thickness of 1.7 nm shows good antifouling ability. E7âmodified substrates have an improving effect on adhesion and spreading of the rat bone marrowâderived mesenchymal stem cells (rBMSCs), along with the increase of E7 densities. rBMSCs on E7âmodified substrates maintain the stem cell phenotypes, and shows robust proliferation and multilineage differentiation, especially on the substrates with high E7 densities. In summary, this study provides a novel strategy of E7 functionalization to promote adhesion and maintain stemness of MSCs, which holds great potentials in the functionalization of microcarriers for the expansion of MSCs.
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