Bioengineering Skin Substitutes for Wound Management-Perspectives and Challenges.

Non-healing wounds and skin losses constitute significant challenges for modern medicine and pharmacology. Conventional methods of wound treatment are effective in basic healthcare; however, they are insufficient in managing chronic wound and large skin defects, so novel, alternative methods of therapy are sought. Among the potentially innovative procedures, the use of skin substitutes may be a promising therapeutic method. Skin substitutes are a heterogeneous group of materials that are used to heal and close wounds and temporarily or permanently fulfill the functions of the skin. Classification can be based on the structure or type (biological and synthetic). Simple constructs (class I) have been widely researched over the years, and can be used in burns and ulcers. More complex substitutes (class II and III) are still studied, but these may be utilized in patients with deep skin defects. In addition, 3D bioprinting is a rapidly developing method used to create advanced skin constructs and their appendages. The aforementioned therapies represent an opportunity for treating patients with diabetic foot ulcers or deep skin burns. Despite these significant developments, further clinical trials are needed to allow the use skin substitutes in the personalized treatment of chronic wounds.

Adipose-Derived Mesenchymal Stromal Cells in Basic Research and Clinical Applications.

Adipose-derived mesenchymal stromal cells (AD-MSCs) have been extensively studied in recent years. Their attractiveness is due to the ease of obtaining clinical material (fat tissue, lipoaspirate) and the relatively large number of AD-MSCs present in adipose tissue. In addition, AD-MSCs possess a high regenerative potential and immunomodulatory activities. Therefore, AD-MSCs have great potential in stem cell-based therapies in wound healing as well as in orthopedic, cardiovascular, or autoimmune diseases. There are many ongoing clinical trials on AD-MSC and in many cases their effectiveness has been proven. In this article, we present current knowledge about AD-MSCs based on our experience and other authors. We also demonstrate the application of AD-MSCs in selected pre-clinical models and clinical studies. Adipose-derived stromal cells can also be the pillar of the next generation of stem cells that will be chemically or genetically modified. Despite much research on these cells, there are still important and interesting areas to explore.

Functionalized Peptide Fibrils as a Scaffold for Active Substances in Wound Healing.

Technological developments in the field of biologically active peptide applications in medicine have increased the need for new methods for peptide delivery. The disadvantage of peptides as drugs is their low biological stability. Recently, great attention has been paid to self-assembling peptides that can form fibrils. Such a formulation makes bioactive peptides more resistant to enzymatic degradation and druggable. Peptide fibrils can be carriers for peptides with interesting biological activities. These features open up prospects for using the peptide fibrils as long-acting drugs and are a valid alternative to conventional peptidic therapies. In our study, we designed new peptide scaffolds that are a hybrid of three interconnected amino acid sequences and are: pro-regenerative, cleavable by neutrophilic elastase, and fibril-forming. We intended to obtain peptides that are stable in the wound environment and that, when applied, would release a biologically active sequence. Our studies showed that the designed hybrid peptides show a high tendency toward regular fibril formation and are able to release the pro-regenerative sequence. Cytotoxicity studies showed that all the designed peptides were safe, did not cause cytotoxic effects and revealed a pro-regenerative potential in human fibroblast and keratinocyte cell lines. In vivo experiments in a dorsal skin injury model in mice indicated that two tested peptides moderately promote tissue repair in their free form. Our research proves that peptide fibrils can be a druggable form and a scaffold for active peptides.