# Concept Justification of Future 3 DPVS and Novel Approach towards its Conceptual Development
## 1 Introduction
### Background and Limitation of Cell Culture and Scaffolding  
To propose the novel concept 3 DPVS, it is necessary to understand the background and limitation of cell culture and scaffolding. First of all, 3D cell culture has developed from 2D cell culture in recent decades, for creating suitable 3D surrounding environments utilized for better cell growth, differentiation and function [1,2]. The limitation of cell culture in terms of dimensionality, for example the flat-monolayer-structure of cells that resulted by 2D culture, was preliminarily addressed by 3 Dculture. 3D scaffolding has been utilized as the means for optimal 3D cell culture, showing tremendous benefits over early 2D cell culture or 3D non-scaffolding methods, in terms of mimicking 3D cell environment in vitro, increasing cell proliferation and differentiation rate [2; 3; 4], as well as helping researchers to explore knowledge of 3D cell culture and tissue growth in general. However, despite the development from 2D tools into 3D scaffolding, which is universally considered as revolutionary, 3D scaffolds in current biomedical or culture cell worlds still remain static or passive, the same as traditional 2D cell culture plates or platforms. This property in 3D scaffolding could contribute to the gap between current and future scaffold engineering. In connection with this, dynamicity is another vital aspect in cell culture. Since dynamicity cannot be enabled by current scaffolding; researchers have to use external means to address the dynamic cell culture purpose. Vibration mechanisms, which can be connected with scaffolding or culturing platforms, have been most widely applied for achieving dynamicity, due to its proven effectiveness and easy applicability. Vibration stimulation helps provide a dynamic environment similar to in vivo conditions, where cells tend to grow in a better and natural way with increased cell adhesion and better differentiation rate etc., [5; 6]. However, two chief limitations exist in such previously applied vibration mechanisms. First, current vibration and dynamicity can only be achieved by outer mechanical stimulations. Bio-reactors, mechanical stimulators and vibrators etc., are popular ways to generate vibrations in vitro. In many cases, cells have to be limited in receiving vibrations through such mechanisms [5; 7]. Three \"layers\" exist regarding the whole cell culture unit, namely external vibrators, cell culture scaffolding, and the cells cultured inside. In contrast, inside the real tissue the dynamic organism is spontaneous and all-in-one, which ensures cells are cultured in an exact and thorough way required by the organism. In this connection, cells could be negatively affected by these intermediate \"layers\" utilizing externally applied vibratory mechanism. For example, vibrations usually have to pass through the vibrators first, then the platform holding the vibrators, the scaffold inside the platform, the inner environment of the scaffold, and then they can finally reach the cells. Therefore, how to shorten the energy path and make vibration from the scaffold within, not without, can be an interesting question. A vibratory scaffold product, therefore, has the potential value to be studied and developed. Second, another limitation in current vibration mechanisms is that vibratory effects have to be \"evenly-distributed\" or identical among different areas inside the scaffold. That is, when external vibration works, all parts of the culturing scaffold have to be vibrated and react passively together. This negatively affects some differentiation and proliferation of cells into 3D tissues when different groups of cells might need a tailored and variable dynamic sub-environment [8; 9; 10]. For instance, some tissues in vivo, like bones, can be divided into different sub tissue groups where stems cells develop in distinctive ways. Distinct parts, therefore, may require different or specific vibratory stimulus or dynamic properties [9; 11; 12; 13; 14].