Benefit of coupling heparin to crosslinked collagen I/III scaffolds for human dermal fibroblast subpopulations' tissue growth.

Currently, there is a lack of models representing the skin dermal heterogeneity for relevant research and skin engineering applications. This is the first study reporting production of dermal equivalents reproducing features of papillary and reticular dermal compartments. Inspired from our current knowledge on the architecture and composition differences between the papillary and reticular dermis, we evaluated different collagen-based porous materials to serve as scaffolds for the three-dimensional expansion of freshly isolated papillary and/or reticular fibroblasts. The scaffolds, composed of either collagen I or collagen I and III mixtures, were prepared by lyophilization. Pore size and hydrolytic stability were controlled by crosslinking with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) or EDC/NHS with covalently bound heparin. The evaluation of the resultant "papillary" and "reticular" dermal equivalents was based on the analysis of characteristic features of each dermal compartment, such as cell density and deposition of newly synthetized extracellular matrix components in histological sections. Crosslinking supported cell growth during dermal tissue formation independent on the fibroblast subpopulation. The presence of collagen III seemed to have some positive but non-specific effect only on the maintenance of the mechanical strength of the scaffolds during dermal formation. Histological analyses demonstrated a significant and specific effect of heparin on generating dermal equivalents reproducing the respective higher papillary than reticular cell densities and supporting distinct extracellular matrix components deposition (three to five times more carbohydrate material deposited by papillary fibroblasts in all scaffolds containing heparin, while higher collagen production was observed only in the presence of heparin).

Fabrication of hollow microneedles using liquid crystal display (LCD) vat polymerization 3D printing technology for transdermal macromolecular delivery.

The present study aimed to fabricate a hollow microneedle device consisting of an array and a reservoir by means of 3D printing technology for transdermal peptide delivery. Hollow microneedles (HMNs) were fabricated using a biocompatible resin material, while PLA filament was used for the reservoirs. The fabricated microdevice was characterized by means of optical microscopy, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), contact angle measurements and leakage inspection studies to ensure the passageway of liquid formulations. Mechanical failure and penetration tests were carried out and supported by Finite Element Analysis (FEA). The cytocompatibility of the microneedle arrays was assessed to human keratinocytes (HaCaT). Finally, the transport of the model peptide octreotide acetate across artificial membranes was assessed in Franz cells using the aforementioned HMN design.

Fabrication and finite element analysis of stereolithographic 3D printed microneedles for transdermal delivery of model dyes across human skin in vitro.

This research aimed to manufacture and evaluate in vitro 3D printed microneedles for transdermal drug delivery. Firstly, microneedle arrays were fabricated using a polymer-based material. Subsequently, these arrays were tested for their mechanical strength applying axial load along their length, while prediction of the buckling load was performed using widely known arithmetic models. Additionally, the force required to pierce human skin was calculated in order to verify that microneedles insert human skin without buckling or fracturing. Finite Element Analysis (FEA) was used to simulate the insertion process and complement the experimental findings. Furthermore, permeation studies were carried out in order to compare diffusion of two model dyes with different molecular weight namely; FITC-Dextran (M.W.:4000 Da) and calcein (M.W.:622.54 Da) across full thickness human skin in vitro before and after skin treatment with microneedles. Finally, visualization studies enabled illustration of microneedle perforation sites. The results showed that the manufactured 3D printed microneedle arrays penetrate sufficiently human skin and can significantly enhance the transport of the dyes across human skin.

Management of the complications of tissue expansion during a 5-year period (2005-2010).

We report our experience of using tissue expansion where we deal particularly with complications and their management. Forty patients had tissue expanded during a 5-year period (2005-2010). Indications included reconstruction of a scar (after a burn, after injury, or postoperative), congenital naevi, microtia, and breast reconstruction after mastectomy. Of the 50 expanders inserted, complications occurred in 12 (10 patients). Exposure and perforation of the expander were the most common complications, followed by infection, seroma, and local pain. In all cases, complications were managed successfully either by conservative treatment or by a single procedure. The reconstructive plan ended in an acceptable aesthetic result in 9 of the 10 complicated areas. The insertion of multiple expanders over extensive scar tissue and particularly over the lower limb, is associated with high morbidity. Selection of patients, identification of high-risk sites, and suggestions for treatment are important. When complications occur, immediate management usually results in a successful outcome.