Dynamic regulation of substrate micro‐structures is an effective strategy to control stem cell fate in tissue engineering. Translating this into in vivo tissue repair in a clinical setting remains challenging, which requires precise temporal control of multi‐scale structural features. Using 4D printing technique, a multi‐responsive bilayer morphing membrane consisting of a shape memory polymer (SMP) layer and a hydrogel layer, is fabricated. The SMP layer is featured with responsive surface micro‐structures, which can switch the phase between proliferation and differentiation precisely, thus promoting the bone formation. The hydrogel layer endows the membrane with the ability to digitally regulate its 3D geometry, matching the specific macroscopic bone shape in clinical scenario. The authors’ in vivo experiments show that the 4D shape‐shifting membrane exhibits over 30% improvement in new bone formation in comparison to a reference membrane with static micro‐structure. More importantly, the 4D membrane can conformally wrap a bone defect model in a non‐invasive way and this strategy can be extended to repairs involving complex tissue defects.
Divalent main-group-elemental
ions are widely used to improve osteogenic
capacity of implants biofabricated from Ti and its alloys. However,
the conclusions regarding their osseointegration and immunogenicity
are always inconsistent because of the multiple bone remodeling processes
as well as the distinct material surface features arising from processing.
Here we successfully manufactured the porous micro/nanostructured
surface topography with divalent main-group-elemental ions (Mg2+, Ca2+, Sr2+, Ba2+) on substrates
through hydrothermal treatment and comprehensively evaluated the complex
bone remodeling processes, including osseointegration, immunogenicity,
and fibrosis of substrates and implants. We found that Sr-modified
implants not only upregulated the adhesion and proliferation of mesenchymal
stem cells but also the differentiation of osteogenic markers compared
with those modified by other divalent main-group-elemental ions (Mg2+, Ca2+, Ba2+). More importantly, the
osteoclastogenesis, immunogenicity, and fibrosis of Sr-modified implants
were also significantly downregulated. In vivo, evaluations
of new bone formation and histological morphology at the interface
of implant and host as well as the removal torque similarly indicated
the improved osseointegration of Sr-modified implants as well as the
absence of immunogenicity, fibrosis, or necrosis. Our results suggested
that among various divalent main-group-elemental ions, Sr2+ might be a promising one for enhancing bone remodeling, which can
be used to instruct functionalization of the surfaces of biofabricated
Ti-based orthopedic and dental implants in the future.
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