Publication date: 25th July 2016
Bone is a unique and highly regenerative tissue in vertebrates. Unlike to most injuries that lead to fibrotic scar formation, bone healing restores pre-fracture properties under optimal conditions. Thus, a scarless repair of structures such as after fracture is possible leading the path to unravel mechanism of true regeneration. An understanding of the underlying mechanisms and processes might serve as blue-print to other organ systems where regeneration appears even more challenging.
The formation of callus tissue proved to be mechano-responsive in both, the type and the amount of tissue formed. All of the relevant cascades of bone healing and formation are directly influenced by mechanical means. The way tissues are formed, the way they mature and aspects of their re-organization are directly influenced by mechanical constrains. Even though the general nature of mechano-sensitivity are widely known, details of their cell-matrix interplay and specially how the mechano-sensitivity at the various length scales are yet not fully understood.
To what degree key-regulators of mechano-sensitivity remain constant with time and across processes such as development, maintenance and adaptation is also relatively unknown. Using mesenchymal stroma cells (MSCs) as a key element of regenerative capacity, studies from our and other groups in humans and animals have demonstrated an age dependent regeneration potential that seems to decline with increasing age. The reduced mechano-sensitivity of one of the key-elements of regeneration – mesenchymal stroma cells - combined with a shift in material characteristics and change in tissue straining in aged species compared to their younger counterparts illustrates the importance to characterize mechano-senstivity of biological systems not as static and somehow stable systems but as adaptive systems with changing capacities in all stages of aging. A further understanding of the underlying mechanism of the link between biology and mechanics and their direct interactions at the various lengths scales and across aging seems to be essential to understand healing cascades, their interaction and limitations in healing in clinically demanding situations. This understanding is mandatory to allow effective stimulation of regenerative cascades in compromised patients.
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