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Abstract Background Bone regeneration research is currently ongoing in the scientific community. Materials approved for clinical use, and applied to patients, have been developed and produced. However, rather than directly affecting bone regeneration, these materials support bone induction, which regenerates bone. Therefore, the research community is still researching bone tissue regeneration. In the papers published so far, it is hard to find an improvement in the theory of bone regeneration. This review discusses the relationship between the existing theories on hard tissue growth and regeneration and the biomaterials developed so far for this purpose and future research directions. Mainbody Highly complex nucleation and crystallization in hard tissue involves the coordinated action of ions and/or molecules that can produce different organic and inorganic composite biomaterials. In addition, the healing of bone defects is also affected by the dynamic conditions of ions and nutrients in the bone regeneration process. Inorganics in the human body, especially calcium- and/or phosphorus-based materials, play an important role in hard tissues. Inorganic crystal growth is important for treating or remodeling the bone matrix. Biomaterials used in bone tissue regeneration require expertise in various fields of the scientific community. Chemical knowledge is indispensable for interpreting the relationship between biological factors and their formation. In addition, sources of energy for the nucleation and crystallization processes of such chemical bonds and minerals that make up the bone tissue must be considered. However, the exact mechanism for this process has not yet been elucidated. Therefore, a convergence of broader scientific fields such as chemistry, materials, and biology is urgently needed to induce a distinct bone tissue regeneration mechanism. Conclusion This review provides an overview of calcium- and/or phosphorus-based inorganic properties and processes combined with organics that can be regarded as matrices of these minerals, namely collagen molecules and collagen fibrils. Furthermore, we discuss how this strategy can be applied to future bone tissue regenerative medicine in combination with other academic perspectives.

Abstract Background Fabrication of three-dimensional stem cell spheroids have been studied to improve stem cell function, but the hypoxic core and limited penetration of nutrients and signaling cues to the interior of the spheroid were challenges. The incorporation of polymers such as silica and gelatin in spheroids resulted in relatively relaxed assembly of composite spheroids, and enhancing transport of nutrient and biological gas. However, because of the low surface area between cells and since the polymers were heterogeneously distributed throughout the spheroid, these polymers cannot increase the cell to extracellular matrix interactions needed to support differentiation. Methods We developed the stem cell spheroids that incorporate poly(ι-lactic acid) single-segmented fibers synthesized by electrospinning and physical and chemical fragmentation. The proper mixing ratio was 2000 cells/μg fibers (average length of the fibers was 50 μm - 100 μm). The SFs were coated with polydopamine to increase cell binding affinity and to synthesize various-sized spheroids. The function of spheroids was investigated by in vitro analysis depending on their sizes. For statistical analysis, Graphpad Prism 5 software (San Diego, CA, USA) was used to perform one-way analysis of variance ANOVA with Tukey’s honest significant difference test and a Student’s t-test (for two variables) (P