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A series of thermoresponsive and biocompatible ABA triblock copolymers in which the outer A blocks comprise poly(N-isopropylacrylamide) and the central B block consists of O-phosphoethanolamine (PEA) grafted poly(acrylic acid) (PAA(PEA)) are achieved by atom transfer radical polymerization (ATRP) and subsequent modification. At a relatively low concentration (2 w/v% in phosphate buffered saline), the triblock copolymers can form free-standing gels at 37 °C. Using a combination of variable-temperature 1H NMR, dynamic light scattering, and rheological measurements, it is demonstrated that the gelation behavior is highly dependent on both the length of A blocks and the substitution degree of phosphate group. To examine the potential application as scaffold for bone tissue engineering, the physical gels are incubated in the simulated body fluid (SBF) for 2 weeks. Obvious nucleation and growth of hydroxyapatite are found in the gels, as indicated by the scanning electron microscope, energy dispersive spectroscopy, and X-ray diffraction measurements. The triblock copolymers also exhibit low cytotoxicity in cell viability test. Thus the triblock copolymers have great potential for bone tissue engineering.

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The study of protein self-assembly has attracted great interest over the decades, due to the important role that proteins play in life. In contrast to the major achievements that have been made in the fields of DNA origami, RNA, and synthetic peptides, methods for the design of self-assembling proteins have progressed more slowly. This Concept article provides a brief overview of studies on native protein and artificial scaffold assemblies and highlights advances in designing self-assembling proteins. The discussions are focused on design strategies for self-assembling proteins, including protein fusion, chemical conjugation, supramolecular, and computational-aided de novo design.

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