Towards the personalization of gelatin-based 3D patches: a tunable porous carrier for topical applications.

Cell-free based therapies, for example, the use of the cell secretome, have emerged as a promising alternative to conventional skin therapies using bioactive and, when combined with 3D printing technologies, allow the development of personalized dosage forms. This research work aimed to develop gelatin-based patches with controlled network topology via extrusion 3D printing, loaded with cell culture medium as a model of the secretome, and applicable as vehicles for topical delivery. Inks were optimized through rheological and printing assays, and the incorporation of medium had minor effects in printability. Regarding network topology, grid infills rendered more defined structures than the triangular layout, depicting clearer pores and pore area consistency. Release studies showed that filament spacing and infill pattern influenced the release of rhodamine B (model bioactive) and bovine serum albumin (model protein). Moreover, the grid patches (G-0.7/1/0.7), despite having around a seven-fold higher mean pore area than 0.7-mm triangular ones (T-0.7), showed a similar release profile, which can be linked to the network topology of the printed structures This work provided insight on employing (bio)printing in the production of carriers with reproducible and controlled pore area, able to incorporate cell-derived secretome and to be quickly tailored to the patient's lesions.

Fabrication of antibacterial and biocompatible 3D printed Manuka-Gelatin based patch for wound healing applications.

Development of multifunctional 3D patches with appropriate antibacterial and biocompatible properties is needed to deal with wound care regeneration. Combining gelatin-based hydrogel with a well-known natural antibacterial honey (Manuka honey, MH) in a 3D patch can provide improved printability and at the same time provide favourable biological effects that may be useful in regenerative wound treatment. In this study, an antibacterial Manuka-Gelatin 3D patches was developed by an extrusion-based printing process, with controlled porosity, high shape fidelity, and structural stability. It was demonstrated the antibacterial activity of Manuka-Gelatin 3D patches against both gram-positive bacteria (S. epidermidis and S. aureus) and gram-negative (E. coli), common in wound infection. The 3D Manuka-Gelatin base patches demonstrated antibacterial activity, and moreover enhanced the proliferation of human dermal fibroblasts and human epidermal keratinocytes, and promotion of angiogenesis. Moreover, the ease of printing achieved by the addition of honey, coupled with the interesting biological response obtained, makes this 3D patch a good candidate for wound healing applications.

On the progress of hydrogel-based 3D printing: Correlating rheological properties with printing behaviour.

One of the exciting future directions in the 3D printing field is the development of innovative personalized smart constructions for bio-applications, including drug delivery, namely high-throughput drug screening and customized topical/oral administration of pharmaceuticals, as well as tissue engineering. In this context, hydrogels have emerged as a promising material that, when combined with extrusion 3D printing, allow the creation of soft-material structures with defined spatial locations, that can be printed at room temperature and customized by tuning the geometric design and/or the formulation components. Thus, the efficacy and quality of such vehicles is dependent on formulation, design, and printing process parameters. However, hydrogel inks are often designed and characterized using different methods and this lack of uniformity impairs. Characterization techniques are usually arbitrary and differ among research groups, challenging the inference of possible conclusions on hydrogel behaviour and potential applications. Therefore, to properly analyse the potential of a particular hydrogel ink formulation, we review, for the first time, the most frequently employed characterization procedures, from rheological approaches to printing parameters and settings, and discuss their relevance, limitations and drawbacks, and highlight future perspectives. Overall, to accelerate the development of high-quality 3D constructs, comprehensive characterization protocols for both pre-printing and printing assays should be adopted. Furthermore, their transversal adoption could serve as a boost in terms of quality requirements and regulatory aspects.

Diving into 3D (bio)printing: A revolutionary tool to customize the production of drug and cell-based systems for skin delivery.

The incorporation of 3D printing technologies in the pharmaceutical industry can revolutionize its R&D, by providing a simple and rapid method to produce tailored one-off batches, each with customized dosages, different compounds, shapes, sizes, and adjusted release rates. Particularly, this type of technology can be advantageous for the development of topical and transdermal drug delivery systems, including patches and microneedles. The use of both systems as drug carriers offers advantages over the oral administration, but the possibility of skin irritation and sensitization, and the high production costs, may hinder the expansion of this market. In this context, 3D printing, a high-resolution technique, allows the design of high quality, personalized, complex and sophisticated structures, thus reducing the production costs and improving the patient compliance. This review covers the 3D printing concept and discusses the relevance of this technology to the pharmaceutical industry, with a special focus on the development of topical and transdermal products - patches and microneedles. The potential of 3D bioprinting for skin applications is also presented, highlighting the development of patch-like skin constructs for wound and burn treatment, and skin equivalents for in vitro research and drug development. Several recent studies were selected to support the relevance of the subjects addressed herein. Additionally, the limitations of these printing technologies are discussed, including regulatory, quality and safety issues.

A mathematical modeling strategy to predict the spreading behavior on skin of sustainable alternatives to personal care emollients.

Spreadability is one of the most important physicochemical properties of cosmetic products, according to the consumer. Thus, it is fundamental to develop strategies with the aim to improve the knowledge and predict the behavior of alternatives to synthetic emollients. The main goal of this research article was to correlate different physicochemical attributes, namely spreading value, apparent viscosity, density, saponification value, iodine value, peroxide value, acid value and melting range, with the spreading behavior of sustainable alternatives for petrolatum and dimethicone. The sensitivity and adequacy of each parameter were statistically analyzed, and the models were built by forward selection. The two adjusted and optimized models include viscosity and density as parameters and, in the petrolatum case, the model further includes the melting range, which was also validated as a significant predictor. Furthermore, it was also possible to compare the data obtained with the consumer's perception of the spreading behavior of the studied raw materials. A strong correlation was observed, suggesting that these tools mirror the consumer opinion. The application of these mathematical models is a valuable tool to assist the entire replacement process, which usually is a time-consuming procedure.

Replacing Synthetic Ingredients by Sustainable Natural Alternatives: A Case Study Using Topical O/W Emulsions.

With the increasing debate on sustainability, there is a strong market trend to formulate more sustainable products for topical application. Several studies emphasize the potential applications of natural, organic, or green chemistry-derived ingredients, but comparative studies between conventional ingredients and sustainable alternatives are lacking. This type of study is considered an excellent baseline and time-saving strategy for future studies. In addition, one of the main challenges of replacing ingredients by sustainable alternatives in topical vehicles is to maintain high-quality products. Thus, the main goal of this research study was to create a well-defined strategy supported by specific experimental data for the development of sustainable topical vehicles with high-quality standards. The study was designed to evaluate the effects of replacing conventional ingredients (e.g., hydrocarbons, silicones, and preservatives) by sustainable ones on the physical, chemical, and microbiological features of topical emulsions. Additionally, in vivo assessment studies were performed to evaluate the safety, biological efficacy, and sensorial aspects of the developed formulations. The results obtained showed that the replacement of ingredients by sustainable alternatives has an effective impact on the physicochemical and structural properties of the emulsions, mainly on their rheological behavior. However, using appropriate strategies for ingredient selection and rheological adjustment, it is possible to overcome some barriers created by the use of natural raw materials, thus developing appealing and high-quality sustainable topical vehicles.

Effects of Starch Incorporation on the Physicochemical Properties and Release Kinetics of Alginate-Based 3D Hydrogel Patches for Topical Delivery.

The development of printable hydrogel inks for extrusion-based 3D printing is opening new possibilities to the production of new and/or improved pharmaceutical forms, specifically for topical application. Alginate and starch are natural polysaccharides that have been extensively exploited due to their biocompatibility, biodegradability, viscosity properties, low toxicity, and relatively low cost. This research work aimed to study the physicochemical and release kinetic effects of starch incorporation in alginate-based 3D hydrogel patches for topical delivery using a quality by design approach. The incorporation of a pregelatinized starch is also proposed as a way to improve the properties of the drug delivery system while maintaining the desired quality characteristics. Critical material attributes and process parameters were identified, and the sensitivity and adequacy of each parameter were statistically analyzed. The impact of alginate, starch, and CaCl2·2H2O amounts on relevant quality attributes was estimated crosswise. The amount of starch revealed a synergetic impact on porosity (p = 0.0021). An evident increase in the size and quantity of open pores were detected in the as printed patches as well as after crosslinking (15.6 ± 5.2 µm). In vitro drug release studies from the optimized alginate-starch 3D hydrogel patch, using the probe Rhodamine B, showed an initial high burst release, followed by a controlled release mechanism. The results obtained also showed that the viscoelastic properties, printing accuracy, gelation time, microstructure, and release rates can be modulated by varying the amount of starch added to the system. Furthermore, these results can be considered an excellent baseline for future drug release modulation strategies.