To engineer bone tissue, an ideal biodegradable implant should be biocompatible, biodegradable, osteoinductive and osteoconductive.

The fabrication of hybrid hierarchical assemblies involving inorganic and organic building blocks has received a significant amount of attention as a result of their facile tunability and potential applications. However, precise design of hybrid hierarchical architectures still remains a challenge because of the difficulty of precise control over design and the incompatibility of organic and inorganic building blocks. Crystallization-driven self-assembly (CDSA) of block copolymers is a powerful method in the preparation of complex semicrystallized structures from the nano- to microscale, with controlled shape and uniform size. Herein, we extended the scope of this methodology in the construction of hybrid micellar CDSA brushes on functionalized carbon nanotubes (CNTs). Tunable brushlike heterostructures containing both CNTs and CDSA nanoassemblies were fabricated by anchoring the short crystalline seeds of PCL-b-P4VP [PCL = poly­(ε-caprolactone) and P4VP = poly­(4-vinylpyridine)] onto CNTs through the hydrogen bond and by a further in situ CDSA process via the addition of PCL-b-PDMA [PDMA = poly­(N,N-dimethylacrylamide)] unimers. More importantly, the shapes of PCL-b-PDMA crystals changed from two-dimensional platelets to long and thin crystals with increasing mass ratios of seed micelles to CNTs. Moreover, further exploration indicated that only one end of the immobilized seeds could initiate the growth of PCL-b-PDMA crystals, while the other end failed to enable growth because of the spatial confinement of CNTs.

Living crystallization-driven self-assembly (CDSA) is a powerful approach to tailor nanoparticles with controlled size and spatially defined compositions from amphiphilic crystalline block copolymers (BCPs). However, a variety of external constraints usually make the successful applications of living CDSA difficult. Herein, such constraints arising from strong hydrogen-bond (H-bond) interactions between unimers that lead to the failure of living CDSA are effectively overcome via reduction of the H-bond strength. In particular, by adding a H-bond disruptor trifluoroethanol (TFE), decreasing the unimer concentration, and reducing the corona segment length, the H-bond strength between unimers could be efficiently alleviated, leading to the formation of uniform two-dimensional (2D) platelets with controlled size and block comicelles with spatially defined corona chemistries. Moreover, by selectively anchoring one-dimensional (1D) seeds on the surface of as-prepared 2D block comicelles through H-bond interaction, the epitaxial growth of a crystalline BCP from immobilized 1D seeds on 2D platelets illustrates competitive growth behavior in a spatially confined environment.

The less invasive approaches of UMIF and MHL greatly preserved the flexion motion (more than 48 %) of the cervical spine compared with laminectomy, and the preserved motion mean the low-risk of postoperative spinal instability. UMIF and MHL also reduced the increased stress of annulus caused by ML, and the lesser stress will lower the risk of postoperative disc degeneration. The posterior bone elements play a slight role in spinal stability after removal of the attached ligaments.

Recent evidence has demonstrated that mesenchymal stem cells (MSCs) can release a large number of functionally specific microRNA (miRNA) microvesicles that play a role in promoting osteogenic differentiation, but the specific mechanism is not yet clear. Under such context, this study aims to elucidate the mechanism of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exo) promoting fracture healing in mice. We isolated and identified the BMSC-Exo. Bioinformatics analysis predicted high expression of miRNA in exosomes and verified the transfer of miR-25 in exosomes by immunofluorescence. Targeting relationship between miR-25 and Smad ubiquitination regulatory factor-1 (SMURF1) was predicted and verified by dual-luciferase reporter gene assay. Immunoprecipitation and protein stability assays were used to detect Runt-related transcription factor 2 (Runx2) ubiquitination and the effect of SMURF1 on Runx2 ubiquitination, respectively. The effect of miR-25 in BMSC-Exo on fracture healing in mice was assessed using X-ray imaging. alkaline phosphatase, alizarin red staining, EdU, CCK-8, and Transwell were used to evaluate the effects of exosomes transferred miR-25 on osteogenic differentiation, proliferation, and migration of osteoblasts. Bioinformatics analysis predicted that miR-25 expression in exosomes increased significantly. Moreover, the targeted regulation of SMURF1 by miR-25 was verified. SMURF1 inhibited Runx2 protein expression by promoting ubiquitination degradation of Runx2. Notably, miR-25 secreted by BMSC-Exo can accelerate osteogenic differentiation, proliferation, and migration of osteoblasts through SMURF1/Runx2 axis. Our results demonstrate that miR-25 in BMSC-Exo regulates the ubiquitination degradation of Runx2 by SMURF1 to promote fracture healing in mice.