Minimally invasive and targeted therapeutic cell delivery to the skin using microneedle devices.

BACKGROUND: Translation of cell therapies to the clinic is accompanied by numerous challenges, including controlled and targeted delivery of the cells to their site of action, without compromising cell viability and functionality. OBJECTIVES: To explore the use of hollow microneedle devices (to date only used for the delivery of drugs and vaccines into the skin and for the extraction of biological fluids) to deliver cells into skin in a minimally invasive, user-friendly and targeted fashion. METHODS: Melanocyte, keratinocyte and mixed epidermal cell suspensions were passed through various types of microneedles and subsequently delivered into the skin. RESULTS: Cell viability and functionality are maintained after injection through hollow microneedles with a bore size ≥ 75 µm. Healthy cells are delivered into the skin at clinically relevant depths. CONCLUSIONS: Hollow microneedles provide an innovative and minimally invasive method for delivering functional cells into the skin. Microneedle cell delivery represents a potential new treatment option for cell therapy approaches including skin repigmentation, wound repair, scar and burn remodelling, immune therapies and cancer vaccines.

Optical analysis of displacement and strain fields on human skin.

BACKGROUND/AIMS: The aim of this article is to propose a new way to measure the mechanical behaviour of skin by using optical analysis software. Some examples on scars and stretch marks show the validity and the prospects of such a method. METHODS: Software is used to compare two states of deformation. The user takes two photos of the skin surface he wants to study, before and after the deformation is applied. The software is used to process the data. RESULTS: The software gives a mapping of the displacement, and strain fields of the area studied. Investigations can be realised in vitro or in vivo, and it is possible to study, for example, cutaneous lesions like scars and stretch marks. CONCLUSIONS: The method presented gives convincing results, which open many prospects in dermatology, surgery and cosmetology.

Nonlinear model of skin mechanical behaviour analysis with finite element method.

BACKGROUND/AIMS: A problem commonly encountered in plastic and reconstructive surgery is the prediction of the stress put on the skin when various types of skin flaps are used. METHODS/RESULTS: We developed a mathematical model based on the finite element method, in order to determine the stress field, by simulating the mechanical behaviour of human skin during wound closure. We chose to take into account the low compressive strength by modifying the mechanical parameters of the model at each step of the calculation. The model has been developed and tested on a diamond-shaped incision and applied on a Limberg incision. CONCLUSION: The results presented are the Von Mises stress in the area of skin around the scar and, when possible, the resultant closure force. They show the relevance of the method.

Gonadectomy in adult life increases tyrosine hydroxylase immunoreactivity in the prefrontal cortex and decreases open field activity in male rats.

The prefrontal cortices in rats participate in a range of cognitive, emotional, and locomotor functions that are dependent on its rich catecholamine innervation. Sex differences identified in many of these functions suggest that the prefrontal cortex is also influenced by gonadal hormones. Previous studies have shown that prefrontal catecholamines can be modified by changes in the hormone environment in developing animals. The present analyses, carried out in male rats gonadectomized as adults, with and without supplementation with testosterone proprionate, and examined at intervals from two days to 10 weeks after surgery, revealed that both the anatomical organization of prefrontal catecholamine afferents, and a behavioral measure sensitive to their selective lesioning remain highly responsive to changes in testicular hormones in adulthood. Thus, gonadectomy in adult male rats rapidly led to a large but transient decrease in the density of tyrosine hydroxylase immunoreactivity in all layers of the dorsal anterior cingulate cortex. This was followed by a sustained period in which immunoreactivity in the supragranular layers returned to levels that were just below normal (between 72 and 79% of normal), and labeling in deep laminae stabilized at considerably elevated innervation densities (approximately 150% of normal). Neither the acute decrease nor the chronic over-innervation characteristic of gonadectomized animals was observed in rats that were gonadectomized and supplemented with testosterone proprionate. Open field activity assessed along a corresponding 10 week timeline showed that gonadectomized animals were significantly less active than hormonally intact controls, a behavioral pattern opposite to the hyperactivity which persists following prefrontal dopamine lesions. Gonadectomized animals supplemented with testosterone proprionate, on the other hand, had open field scores that were not significantly different from controls. Taken together, these findings indicate that the adult hormone environment provides a significant, and seemingly functionally significant influence over the catecholamine innervation of the rat prefrontal cortex. Such lifelong responsiveness of the prefrontal cortical catecholamines to circulating hormones suggests that gonadal steroids are an active component of the biology of normal adult cognition, and may also have relevance for cortical dysfunction in disorders such as schizophrenia which are not only strongly tied to the catecholamines, but exhibit considerable biases among men and women as well.