Biomimetic Mineralized 3D-Printed Polycaprolactone Scaffold Induced by Self-Adaptive Nanotopology to Accelerate Bone Regeneration.

Three-dimensional (3D)-printed biodegradable polymer scaffolds are at the forefront of personalized constructs for bone tissue engineering. However, it remains challenging to create a biological microenvironment for bone growth. Herein, we developed a novel yet feasible approach to facilitate biomimetic mineralization via self-adaptive nanotopography, which overcomes difficulties in the surface biofunctionalization of 3D-printed polycaprolactone (PCL) scaffolds. The building blocks of self-adaptive nanotopography were PCL lamellae that formed on the 3D-printed PCL scaffold via surface-directed epitaxial crystallization and acted as a linker to nucleate and generate hydroxyapatite crystals. Accordingly, a uniform and robust mineralized layer was immobilized throughout the scaffolds, which strongly bound to the strands and had no effect on the mechanical properties of the scaffolds. In vitro cell culture experiments revealed that the resulting scaffold was biocompatible and enhanced the proliferation and osteogenic differentiation of mouse embryolous osteoblast cells. Furthermore, we demonstrated that the resulting scaffold showed a strong capability to accelerate in vivo bone regeneration using a rabbit bone defect model. This study provides valuable opportunities to enhance the application of 3D-printed scaffolds in bone repair, paving the way for translation to other orthopedic implants.

Universal DNA-Based Sensing Toolbox for Programming Cell Functions.

By recombining natural cell signaling systems and further reprogramming cell functions, use of genetically engineered cells and bacteria as therapies is an innovative emerging concept. However, the inherent properties and structures of the natural signal sensing and response pathways constrain further development. We present a universal DNA-based sensing toolbox on the cell surface to endow new signal sensing abilities for cells, control cell states, and reprogram multiple cell functions. The sensing toolbox contains a triangular-prismatic-shaped DNA origami framework and a sensing core anchored inside the internal confined space to enhance the specificity and efficacy of the toolbox. As a proof of principle, the sensing toolbox uses the customizable sensing core with signal sensing switches and converters to recognize unconventional signal inputs, deliver functional components to cells, and then control cell responses, including specific tumor cell death, immune cell disinhibition and adhesion, and bacterial expression. This work expands the diversity of cell sensing signals and reprograms biological functions by constructing nanomechanical-natural hybrid cells, providing new strategies for engineering cells and bacteria in diagnosis and treatment applications.

Scalable Fabrication of Polymeric Composite Microspheres to Inhibit Oral Pathogens and Promote Osteogenic Differentiation of Periodontal Membrane Stem Cells.

Periodontitis is a worldwide bacterial infectious disease, resulting in the resorption of tooth-supporting structures. Biodegradable polymeric microspheres are emerging as an appealing local therapy candidate for periodontal defect regeneration but suffer from tedious procedures and low yields. Herein, we developed a facile yet scalable approach to prepare polylactide composite microspheres with outstanding drug-loading capability. It was realized by blending equimolar polylactide enantiomers at the temperature between the melting point of homocrystallites and stereocomplex (sc) crystallites, enabling the precipitation of sc crystallites in the form of microspheres. Meanwhile, epigallocatechin gallate (EGCG) and nano-hydroxyapatite were encapsulated in the microspheres in the designated amount. Such an assembly allowed the fast and sustained release of EGCG and Ca2+ ions. The resultant hybrid composite microspheres not only exhibited strong antimicrobial activity against typical oral pathogens (Porphyromonas gingivalis and Enterococcus faecalis), but also directly promoted osteogenic differentiation of periodontal ligament stem cells with good cytocompatibility. These dual-functional composite microspheres offer a desired drug delivery platform to address the practical needs for periodontitis treatment.