# Tuning the Cell and Biological Tissue Environment through Magneto-Active Materials
## 2 Mechanically Mediated Biological Processes
### Mechanical Effects on Bone Development and Healing  
Many mechanical factors play a significant role in bone development and in the healing process. Bones as an organ system are particularly sensitive to mechanical stimuli: a fully developed skeleton continues changing through the course of its life, influenced, shaped, strengthened and weakened by the multiple mechanical forces acting upon it. The different stages of bone creation, development and healing are affected and regulated by the collective mechanical environment [3; 4; 21; 22]. **Mechanics on osteogenesis:** Fundamentally, external stimulation is a key variable in the creation of bone. Dating back to 1892, [PERSON]'s law on bone remodelling proposes how bone density is affected by external loads, nutritional factors, and metabolism [23]. [PERSON]'s experiments involved applying external forces directly, leading to an observable change in bone density, indicating growth. Conversely, the absence of forces has the opposite effect,weakening the bones and increasing the risk of atrophy [24]. Osteogenesis, the creation of bone cells, requires a stable mechanical environment to succeed. [PERSON] hypothesis postulates that mechanical deformation results in the production of connective tissue, hydrostatic compression causes cartilage formation, and their combination leads to the appearance of fibrocartilage [25]. These mechanical dependences have been modelled, as in the work by [PERSON] and [PERSON] [26], which presented a model correlating hydrostatic pressure and strain rates to different types of ossification. Overall, the environmental mechanical properties promote the formation of the tissue that better adapt to the surrounding by means of stress and deformation compatibility. Softer tissue is promoted within soft mechanical environments while stiffer tissue formation is favoured within the stiffer regions. In this approach, intramembranous ossification occurs for low strains and compressive pressures (less than 5% and less than 0.15 MPa, respectively), whereas endochondral bone formation occurs at larger strain levels. Similarly, cartilage formation is promoted within high compression zones (performing a shock absorption role) and fibrocartilage within high strain regions (tolerating high deformation) [26; 27]. **Mechanics on bone fracture:** In bone fractures, the body is capable of sequentially producing the specific physical conditions needed for the reconstruction process. Following an accident, the body forms a hematoma in situ, where signalling molecules are released (cytokines and growth factors). The hematoma increases the volume and pressure at the wound through inflammation. This hematoma acts as the first \"filling\" agent, providing structural support for cells and kickstarting their differentiation into fibrous tissue, cartilage, and bone. If the hematoma phase is interrupted, the sufficient stability conditions for regeneration are not fulfilled, causing delayed or failed healing [28]. Following the inflammatory phase and once initial stabilisation is reached, a tight union (bones fixed together) at sufficient high pressure leads to primary bone healing. In primary healing, a callus does not form, and tissue is healed directly by osteoclast and osteoblast activities. Given that bone is essentially restored to its previous state, the volume remains constant [29]. In the case of joints, primary healing is desired but not always possible, and an open reduction (surgical fixation of the area) may be necessary to guarantee a stiff union [30]. Bone forms when external stimulation is kept to a minimum, but the ideal mechanical environment for bone healing and its normal active state differ. While minimum disturbance supports healing, it can also cause healthy bone atrophy and be reabsorbed. Other factors than fixation stability, such as age of the wound and subject and nature of the wound also play a role [31].