The following study provides a new paradigm in inducing longitudinal bone growth in adults. Cartilage versus Bone cell differentiation is movement based and bone is stiff. If bone tissue was exposed to more deformation(like that which occurs at a joint) then cartilage differentiation could occur and neo growth plate formation is one possible result. LSJL is one possible mechanism for inducing this deformation as bone is more malleable in the lateral direction than the axial direction that occurs more frequently in physiological loading.
This paradigm opens the possibility for other ways to deform the bone to encourage chondrogenic differentiation within the bone to form new growth plates.
Pressureless mechanical induction of stem cell differentiation is dose and frequency dependent.
“Pressureless, soft mechanical stimulation precipitated by the cyclic deformation of soft, magnetic hydrogel scaffolds with an external magnetic field, can induce chondrogenesis in mesenchymal stem cells without any additional chondrogenesis transcription factors (TGF-β1 and dexamethasone). A systematic study on the role of movement frequency revealed a classical dose-response relationship for human mesenchymal stem cells differentiation towards cartilage using mere mechanical stimulation.”
“Diffusion, local release of growth factors and concentration gradients shape an organism’s 3D structure. Unfortunately, liquid filled pockets and particularly movement destroy such local information pattern (e.g. in a joint)
”
“Hip joint (anatomy, a) with a local concentration profile of a differentiation factor secreted at the interface of the cartilage if the joint is not moved (hypothetical, b) and under physiologic movement (c). Diffusion alone usually results in rather steep concentration gradients (static situation). Movement induces liquid mixing through convection (synovial fluid) flattening concentration profiles. ”
” Chondrocyte growth has been associated with demanding physical input such as cell deformation, hydrostatic pressure gradients, fluid flow, streaming currents and physicochemical changes”<-LSJL could potentially alter all of these.
“Without adequate traumatic surgery or fixation, pseudoarthrosis may occur at non-fixed bone fracture sites. Continued movement of such non-fixed primary callus then promotes local stem cell differentiation into cartilage and ligament tissue instead of bone tissue.”<-Mimicking this concept without the fracture may enable neo-growth plate formation.
“If a joint is not moved anymore (e.g. due to arthritis), even an otherwise fully functional joint stiffens (ankylosis) and the tissue locally transforms into a bone-type material”
So movement tends to encourage cartilage growth whereas lack of movement encourages bone growth. The bone changes in length constantly as noted by the definition of microstrain(which measures strain as change in bone length). So natural movement is not enough. However, something like LSJL may mimic such movement via lateral bone deformation as bone is more malleable from a lateral direction than an axial direction.
Bone bending and twisting does occur in a natural environment. It’s just that the natural loads that occur are not enough movement to encourage cartilage over bone stem cell differentiation.
“For the impact of mechanical stimulation at different intensities regarding to differentiation, the stimulus was performed in 30 min cycles every 1.5 h for 8 h per day during 3 weeks (daytime activity, total number of cycles = 12600, 2016 and 672 respectively) for each group (n = 3). Cell culture samples were taken after 1, 2 and 3 weeks, respectively.”
“The only difference between differentiating and non-differentiating hMSC seeded on the scaffolds used here, was the application of the external magnetic field and the resulting reversible, soft deformation of the scaffold. “
