Mechanobiology-Inspired Approaches for Preventatively Accelerating Cell and Tissue Micro-Repair

Background: Pressure ulcer (PU) prevention is the only effective strategy for decreasing occurrence. PUs may occur in soft tissues that are damaged by sustained mechanical loads, e.g. in immobile subjects with reduced sensory-capacity. Localized, sustained mechanical deformations (strains) and stresses can structurally damage and kill cells at susceptible sites. Death of individual cells onsets microscopic damage, which may progress to macroscopic tissue-scale damage, a wound. We aim to develop mechanobiology-inspired approaches to prolong the safe time in an immobile position e.g. during planned surgery, by preventatively extending cell survival and accelerating repair of microscopic damage.

Methods: We combine low-level non-damaging stretching with sodium pyruvate (NaPy) cell-supplement added (in vitro) prior to and/or following induction of damage; stretching is applied by a 3D printed cell-stretching apparatus. We evaluate changes to membrane permeability (indicating reduced cell-homeostasis) under NaPy pre-treatment, and measure migration rates during closure of locally induced micro-scale gaps in cell-monolayers modeling skin and deeper tissues.

Results: Pretreating cells with NaPy prior to onset of damaging-level strain (12%) significantly reduced the strain-damage induced, plasma membrane permeability that can lead to loss of cell homeostasis. Concurrently, we demonstrated that closure of micro-scale gaps, an initial stage of PU formation, can be accelerated by combining externally applied, low-level (non-damaging) 3-6% strains with the NaPy pre-treatment.

Conclusion: NaPy (pre)treatment can preventatively increase cell-level resistance to sustained-deformation-inflicted damage and accelerate closure associated micro-scale gaps when combined with low-level stretching. The synergistic, prophylactic pre-treatment may delay the onset of PUs (Weihs and Gefen PCT/IL2018/051424).