Stem cell-based and stem cell-derived exosome-based therapies have shown promising potential for endometrial regeneration and the clinical treatment of intrauterine adhesions (IUAs). Evidence shows that apoptosis occurs in a majority of grafted stem cells, and apoptotic bodies (ABs) play a critical role in compensatory tissue regeneration. However, the therapeutic potential of AB-based therapy and its mechanism have not been explored in detail. Here, a cell-free therapeutic strategy was developed by incorporating mesenchymal stem cell-derived ABs into a hyaluronic acid (HA) hydrogel to achieve endometrial regeneration and fertility restoration. Specifically, we found that the ABs could induce macrophage immunomodulation, cell proliferation, and angiogenesis
in vitro
. The HA hydrogel promoted the retention of ABs and facilitated their continuous release. In a murine model of acute endometrial damage and a rat model of IUAs,
in situ
injection of the AB-laden HA hydrogel could efficiently reduce fibrosis and promote endometrial regeneration, resulting in the fertility restoration. Consequently, ABs show good potential as therapeutic vesicles, and the AB-laden HA hydrogel appears to be a clinically feasible and cell-free alternative for endometrial regeneration and IUA treatment.
Immune
response is critical to tissue repair. Designing biomaterials
with immunomodulatory functions has become a promising strategy to
facilitate tissue repair. Considering the key roles of macrophages
in tissue repair and the significance of the balance of M1 and M2,
smart biomaterials, which can harness macrophage phenotypes dynamically
to match the tissue healing process on demand, have attracted a lot
of attention to be set apart from the traditional anti-inflammatory
biomaterials. Here, we prepare a gold nanorod-contained shape memory
polycaprolactone film with dynamic surface topography, which has the
ability to be transformed from flat to microgrooved under near-infrared
(NIR) irradiation. Based on the close relationships between the morphologies
and the phenotypes of macrophages, the NIR-triggered surface transformation
induces the elongation of macrophages, and consequently the upregulated
expressions of arginase-1 and IL-10 in vitro, indicating the change
of macrophage phenotypes. The sequential modulation of macrophage
phenotypes by dynamic surface topography is further confirmed in an
in vivo implantation test. The healing-matched modulation of macrophage
phenotypes by dynamic surface topography without the stimuli of cytokines
offers an effective and noninvasive strategy to manipulate tissue
regenerative immune reactions to achieve optimized healing outcomes.
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