Biochemical and structural cues of 3D-printed matrix synergistically direct MSC differentiation for functional sweat gland regeneration.

Mesenchymal stem cells (MSCs) encapsulation by three-dimensionally (3D) printed matrices were believed to provide a biomimetic microenvironment to drive differentiation into tissue-specific progeny, which made them a great therapeutic potential for regenerative medicine. Despite this potential, the underlying mechanisms of controlling cell fate in 3D microenvironments remained relatively unexplored. Here, we bioprinted a sweat gland (SG)-like matrix to direct the conversion of MSC into functional SGs and facilitated SGs recovery in mice. By extracellular matrix differential protein expression analysis, we identified that CTHRC1 was a critical biochemical regulator for SG specification. Our findings showed that Hmox1 could respond to the 3D structure activation and also be involved in MSC differentiation. Using inhibition and activation assay, CTHRC1 and Hmox1 synergistically boosted SG gene expression profile. Together, these findings indicated that biochemical and structural cues served as two critical impacts of 3D-printed matrix on MSC fate decision into the glandular lineage and functional SG recovery.

The early management of the burn wound and observations on hypertrophic scarring. With special reference to the deep dermal level and hypertrophic scarring.

Much confusion about the management of the burn wound still exists in many a clinician's mind. This is an attempt to clarify the problem and create a better understanding of the importance of assessing the various depths of penetration of the thermal agent. The treatment varies from the use of minimal bland dressings left undisturbed to aggressive early tangential excision and skin grafting. This is discussed together with the rationale for this approach and some problems associated with it. A 'critical depth' of penetration at the deep dermal level, which spares the acini of the sweat glands, is suggested as the factor initiating later development of hypertrophic scarring. This can be prevented by early excision and skin grafting.

Cholinergic phenotype developed by noradrenergic sympathetic neurons after innervation of a novel cholinergic target in vivo.

Mammalian sympathetic neurons in vivo may express either a noradrenergic or cholinergic phenotype. In view of the opposing effect of noradrenaline and acetylcholine on most autonomic target organs, the target-appropriate expression of neurotransmitter is critical. We have examined the maturation of the sympathetic innervation of rat sweat glands to define the developmental mechanisms regulating neurotransmitter choice in vivo. Eccrine sweat glands and their sympathetic innervation develop together postnatally in the rat. Early postnatal innervation expresses only noradrenergic properties, but as the glands and their innervation mature, noradrenergic properties decrease dramatically and cholinergic features appear in the same population of neurons. To investigate the role of the sweat gland in this change we have used a transplantation paradigm which allows sweat glands to be innervated by sympathetic neurons that would normally innervate noradrenergic target organs and remain noradrenergic throughout life. We observe that the sympathetic neurons that innervate the novel cholinergic target alter their neurotransmitter properties and develop a cholinergic phenotype. These results indicate that target organs are able to induce appropriate neurotransmitter traits in the neurons that innervate them.