# Tuning the Cell and Biological Tissue Environment through Magneto-Active Materials
## 2 Mechanically Mediated Biological Processes
### Mechanical Effects on Bone Development and Healing
If instead of a rigid environment, the bones are allowed a small degree of motion, secondary healing occurs, where a soft callus forms in the gap area. Bone formation with interfer fragmentary motion needs the presence of the bridging callus, tissue that forms to connect two broken pieces of bone, only appearing under specific strain rates. This soft callus formation (proliferative) phase develops through two processes: (i) endochondral ossification, where Mesenchymal Stem Cells (MSCs) differentiate into chondrocytes, creating cartilage tissue; and (ii) intramembranous ossification, where MSCs differentiate into osteoblasts and bone is directly created. In the latter, the resulting cartilage extracellular matrix mineralizes, and osteoblasts can lay down bone tissue. Next, in the hard callus formation (maturing or modelling) phase, the generated cartilage is used as a support scaffold, and mineralized into bone matter by the osteoblasts [32; 33]. The final stage is the remodelling phase, in which secondary bone formation occurs, reshaping and reabsorbing bone, as needed, to restore the initial shape and strength [34]. If the necessary physical conditions are not maintained, however, it may not be possible to ensure ideal conditions in all scenarios. Failing to fixate bones properly after a fracture or providing too strict a support may cause the process to halt or revert. If high strain exists at the fracture site during the initial stages of formation, fibrous tissue cannot be replaced by bridging callus tissue, resulting in a failed fibrous non-union [35]. As mentioned before, the creation of new bone is not ideal in articulations, as the formation of a callus could interfere with normal activity, and thus normally relies on external or surgical fixation. Moreover, bone healing does not only depend on the magnitude and nature of the forces applied, but also their frequency of application, with evidence of the possible effect on the formation of connective tissue. Regarding the distraction rate (tension applied to the bone in mm/day), contradictory studies exist, suggesting both the independence and negative effect on the healing process. [PERSON] proposes an unequal response to compression and tension to explain this inconsistency, with evidence suggesting that compression is necessary or beneficial to some healing processes [36]. Macro forces acting on the tissue, such as strain, pressure, stability, and fluid velocity are known to have a mechanical effect on the individual cell matrix, affecting their function, migration, and differentiation, but the interrelation remains poorly understood. Other works on both experimental and computational modelling of bone healing can be found in the literature [37; 38; 39]. Mechanical Effects on Collective Cell Migration Underlying Morphogenesis Tissue Regeneration and Cancer Progression  
Collective cell migration is a major player in different biological processes, such as wound healing, embryonic development, or cancer progression. In such migration, cells move as sheets, strands, clusters or ducts, rather than individually. In collective cell migration, cells use similar actin- and myosin-mediated protrusions and guidance by extrinsic chemotactic and mechanical cues, such as that exploited by single migratory cells. However, cadherin-based junctions between cells adds'supracellular' properties, such as collective polarisation, force generation, decision making and, eventually, complex tissue organisation [40]. An additional force-generating property, the ability to generate cell protrusions, also contributes to active motility. These mechanical properties can be regulated independently in cells, suggesting that they can be employed in a combinatorial manner. This could generate a diverse array of cell shapes and arrangements orchestrating the varied morphogenetic events observed during organ development. During these processes, cells continuously interact between them and with their surroundings, i.e., extracellular matrix (ECM).