Molecularly engineered metal-based bioactive soft materials – Neuroactive magnesium ion/polymer hybrids

Abstract The development of bioactive soft materials that can guide cell behavior and have biomimetic mechanical properties is an active and challenging topic in regenerative medicine. A common strategy to create a bioactive soft material is the integration of biomacromolecules with polymers. However, limited by their complex structures and sensitivity to temperature and chemicals, it is relatively difficult to maintain the bioactivity of biomacromolecules during their preparation, storage, and application. Here, a new kind of bioactive soft material based on the molecular integration of metal ions and polymers is designed and exemplified by a hybrid of magnesium ion (Mg 2+ ) and poly(glycerol-sebacate-maleate) (PGSM-Mg). Mg 2+ was firmly incorporated into PGSM molecules through a complexation interaction as evidenced by X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FTIR). The PGSM matrix provided the soft nature and facile processing of the hybrid, which could serve as an injectable material and be fabricated into elastic porous three-dimensional (3D) scaffolds. The Mg 2+ immobilized in the PGSM chain conferred neuroactivity to the resultant hybrid. PGSM-Mg exhibited adequate biodegradability and a sustained release of Mg 2+ . PGSM-Mg 3D scaffolds promoted the adhesion and proliferation of Schwann cells (SCs) more effectively than poly(lactic- co -glycolic acid) (PLGA) scaffolds. Furthermore, SCs on PGSM-Mg scaffolds expressed significantly more neural specific genes than those on PLGA, PGS, and PGSM, including nerve growth factor (NGF) and neurotrophic factor-3 (NTF3). All these results indicated that Mg 2+ immobilized through molecular integration could efficiently regulate the bioactivity of polymers. In view of the wide availability, diverse bioactivity, and high stability of metal ions, the strategy of molecular coupling of metal ions and polymers is expected to be a new general approach to construct bioactive soft materials. Statement of Significance Bioactive soft materials are designed on the basis of the molecular integration of metal ions and polymers. Immobilized metal ions offer a new way to endow bioactivity to polymers. Different from biomolecules such as proteins and genes, metal ions are quite stable and can resist harsh processing conditions. Further, the polymeric matrix provides the soft nature and facile processing of the hybrid. Different from stiff metal-containing inorganic materials, the hybrid is a biomimetic soft material and can be readily processed just like its polymer precursor under mild conditions. In view of the diversity of metal ions and polymers, this strategy is expected to be a new powerful and general approach to construct bioactive soft materials for a wide range of biomedical applications.