Current Pharmaceutical Design - Volume 23, Issue 24, 2017

The global volume of skin damage or injuries has major healthcare implications and, accounts for about half of the world's annual expenditure in the healthcare sector. In the last two decades, tissue-engineered skin constructs have shown great promise in the treatment of various skin-related disorders such as deep burns and wounds. The treatment methods for skin replacement and repair have evolved from utilization of autologous epidermal sheets to more complex bilayered cutaneous tissue engineered skin substitutes. However, inadequate vascularization, lack of flexibility in drug/growth factors loading and inability to reconstitute skin appendages such as hair follicles limits their utilization for restoration of normal skin anatomy on a routine basis. Recent advancements in cutting-edge technology from stem cell biology, nanotechnology, and various vascularization strategies have provided a tremendous springboard for researchers in developing and manipulating tissue engineered skin substitutes for improved skin regeneration and wound healing. This review summarizes the overview of skin tissue engineering and wound healing. Herein, developments and challenges of various available biomaterials, cell sources and in vitro skin models (full thickness and wound healing models) in tissue-engineered skin research are discussed. Furthermore, central to the discussion is the inclusion of various innovative strategies starting from stem cells, nanotechnology, vascularization strategies, microfluidics to three dimensional (3D) bioprinting based strategies for generation of complex skin mimics. The review then moves on to highlight the future prospects of advanced construction strategies of these bioengineered skin constructs and their contribution to wound healing and skin regeneration on current practice.

Tendon injury is a clinical, societal and economical issue. Moreover, tendon repair represents an important clinical challenge, partly due to the mechanical constraints that occur at the junctions with muscle and bone. Several strategies have been developed for tendon repair. In this review, we first assess the importance of tendon injuries from different sites and their causes. After a short overview of tendon three-dimensional organization, the complexity of the perfect repair quest is presented ranging from current clinical procedures to new engineering scaffolds. We then sum up tendon engineering requirements and focus on new collagen-based scaffolds, which raise promising prospects to mimic and repair tendon. In particular, we survey quantitatively a large panel of techniques to produce these scaffolds, detailing their principle and recent improvements.

Incorporating therapeutic molecules into biomorphic ceramics for in situ drug release can be used to generate novel systems for tissue regeneration. These systems couple the complex hierarchical porous structures of biomorphic ceramics with the therapeutic activity of drugs. There are a large number of natural precursors available to be used as templates to obtain biomorphic silicon carbide ceramics. Additionally, different drug loading techniques can be used for these systems. The high versatility in structures and drugs allows the selection of the right structure-drug fit in each case according to the tissue needs. This paper reviews the utility of biomorphic ceramics for tissue engineering as well as their use for local drug release.

Nanotechnology is an exciting emerging field with multiple applications in skin regeneration. Nanofibers have gained special attention in skin regeneration based on their structural similarity to the extracellular matrix. A wide variety of polymeric nanofibers with distinct properties have been developed and tested as scaffolds for skin regeneration. Besides providing support for tissue repair, nanofibrous materials can act as delivery systems for drugs, proteins, growth factors, and other molecules. Moreover, the morphology, biodegradability, and other functionalities of nanofibrous materials can be controlled towards specific conditions of wound healing. Other nanostructured drug delivery systems, such as nanoparticles, micelles, nanoemulsions, and liposomes, have been used to improve wound healing at different stages. These nanoscale delivery systems have demonstrated several benefits for the wound healing process, including reduced cytotoxicity of drugs, administration of poorly water-soluble drugs, improved skin penetration, controlled release properties, antimicrobial activity, and protection of drugs against light, temperature, enzymes or pH degradation, as well as stimulation of fibroblast proliferation and reduced inflammation.

A cut or break on the surface of the skin is usually referred to as a wound. Any wound has a potential to heal by itself through a complex cascade of events. However, some wounds show delayed healing due to their underlying physiology and are referred to as chronic wounds like diabetic ulcers, venous ulcers, pressure ulcers and chronic infected ulcers. Extensive care has to be taken for the management of chronic wounds and these have become a major concern in the current medical scenario. The use of bioactive molecules or in other words the molecules that can actively interact with the wound environment and help in wound healing are gaining much importance. The incorporation of bioactive molecules into a suitable matrix system which not only provide a controlled release of the molecules, but also enable better exudate management is desired to overcome the shortcomings of the conventional treatment modalities. A major problem associated with chronic wounds is that they are easily prone to infections. In such cases, the topical delivery of antibiotics helps eliminate infection. However, the continuous use of high dose of antibiotics has led to the development of multi drug resistant bacterial strains. To overcome these issues, other broad-spectrum antimicrobial agents like antiseptics, metallic nanoparticles and antimicrobial peptides are being adopted nowadays. Growth factors play a major role in the wound healing cascade, thus topical delivery of growth factor from a suitable matrix is an interesting strategy. The delivery of nucleic acids with the aid of suitable vectors for either silencing a particular gene or over expressing a gene of interest is also being investigated nowadays. This review is an attempt to draw light over some of the recent approaches adopted for the treatment of chronic wounds using bioactive molecules like antibiotics, antiseptics, metallic nanoparticles or ions, growth factors and nucleic acids.

Nanobiomaterials can be defined as materials interacting with and influencing the biological microenvironment at a nanointerface. Recently the basic as well as applied research related to nanobiomaterials - a conjugation of nano-, material- and life-sciences - has immensely evolved for therapeutics and related biotechnology areas. The current overview focused on the potential of nanobiomaterial-based substrates towards the generation of biocompatible surfaces, tissue engineering architectures, and regenerative medicine. Emphasis was given to chemomolecular functionalization of nanobiomaterials, nanobiomaterial composites, and morphomechanically modified nanoarchetypes and their inherent chemo-biological interaction with the biological microenvironment. Additionally, recent developments in nanobiomaterial substrate design and structure, chemo-biological interface related bio-systems uses and further evolving applications in health care, therapeutics and nanomedicine were discussed herein. Furthermore, a special emphasis was placed on the nano-chemo-biological interactions inherent to various nanobiomaterial substrates in close vicinity with biological systems.

Our review is focused on the use of methotrexate in drug therapy of two autoimmune diseases, psoriasis and rheumatoid arthritis (RA). The article describes the pathogenesis of psoriasis and RA, the role of methotrexate in the treatment of these diseases with more focused review on the mechanism behind the clinical benefits of methotrexate therapy. Methotrexate due to its cytotoxic, anti-inflammatory and immune modulatory activities provides clinical benefits in the therapy of the selected diseases. This review also gives a panorama of the problems associated with the use of methotrexate in the selected diseases and the guidelines provided by FDA for its safe use. The novel colloidal drug delivery systems of methotrexate, with particular emphasis on advantages offered by liposomal formulation, niosomal gel, hydrogel, albumin conjugates, nanoparticles and nano structured lipid carriers in psoriasis and RA are also reviewed. It seemed that the use of newer colloidal carriers with improved skin permeability by minimizing its systemic availability will be a useful strategy to reduce the toxic effects of the drug in psoriatic patients. In rheumatoid arthritis patients, the development of newer therapeutic strategies using appropriate targeting ligands that specifically deliver the drug to the inflamed joint space will help to overcome its toxic effects by minimizing the systemic exposure.

Tissue engineering is considered one of the most important therapeutic strategies of regenerative medicine. The main objective of these new technologies is the development of substitutes made with biomaterials that are able to heal, repair or regenerate injured or diseased tissues and organs. These constructs seek to unlock the limited ability of human tissues and organs to regenerate. In this review, we highlight the convenient intrinsic properties of gelatin for the design and development of advanced systems for tissue engineering. Gelatin is a natural origin protein derived from collagen hydrolysis. We outline herein a state of the art of gelatin-based composites in order to overcome limitations of this polymeric material and modulate the properties of the formulations. Control release of bioactive molecules, formulations with conductive properties or systems with improved mechanical properties can be obtained using gelatin composites. Many studies have found that the use of calcium phosphate ceramics and diverse synthetic polymers in combination with gelatin improve the mechanical properties of the structures. On the other hand, polyaniline and carbon-based nanosubstrates are interesting molecules to provide gelatin-based systems with conductive properties, especially for cardiac and nerve tissue engineering. Finally, this review provides an overview of the different types of gelatin-based structures including nanoparticles, microparticles, 3D scaffolds, electrospun nanofibers and in situ gelling formulations. Thanks to the significant progress that has already been made, along with others that will be achieved in a near future, the safe and effective clinical implementation of gelatin-based products is expected to accelerate and expand shortly.

Natural products remain the best resources of drugs and drug leads. Recently, there is growing recognition that identifying new small molecules to promote bone regeneration is a laudable translational goal. In fact, new approaches for bone repair and regeneration that involve inexpensive naturally-derived compounds would have an important impact on the treatment of bone disorders and injuries. Over the past several decades, a number of naturally-derived small molecules with the potential of regenerating bone tissue (i.e. osteoinductive) have been reported in the literature. Here, we review the current literature, paying attention to the prospects for natural small molecule-based bone regenerative engineering. We also review various delivery strategies of the selected naturally- derived small molecules for bone regenerative engineering applications.

The emergence of injectable hydrogels as biomaterials has been a revolutionary breakthrough in the field of on-demand drug delivery and tissue engineering. The promising features of these systems include their biodegradability, biocompatibility, permeability, ease of the surgical implantation, and most importantly exhibit minimally invasiveness. These hydrogels have been explored as sustained and on-demand release carriers for the various bioactive agents, growth factors, live cells, various hydrophobic drugs and as extracellular matrices for tissue engineering. Present review is an attempt to highlight the recent systems explored for on-demand drug release and tissue engineering. It also gives an overview of the role of nanotechnology in the advancements of injectable hydrogels. The future prospects and challenges of these hydrogels have also been addressed.

Following fertilization, the blastocyst has to complete two distinct steps to assure further development of pregnancy. After apposition it establishes a firm connection with the luminal epithelium of the endometrium (attachment) and subsequently enters the decidualizing stroma (invasion). If this step is not achieved successfully, fertility problems arise. Development of the placenta ensures an adequate supply of nutrients and gas between the mother and the fetus. Preeclampsia is a prevalent disorder arising from defects in the process of placentation. It is associated with an increase of maternal morbidity and mortality. Numerous attempts have been made in order to elucidate the etiology of the syndrome and identify women at risk. The lack of reliable animal models has turned the attention to the development of in vitro assays, which could provide a better insight into the individual processes that will later trigger preeclampsia symptoms. In particular, 3D in vitro models more closely resemble the complexity of the extracellular environment. The choice of the scaffolding material should be done carefully as cell-matrix interactions are very often as important as cell-cell interactions for the correct attachment, proliferation and differentiation of cells. The following review is aimed to provide a general overview of the scaffolds available for the in vitro modeling of these complicated systems as well as to discuss the importance surrounding the choice of the scaffolding material and its influence on the results obtained.

Gene therapy may be capable of treating a variety of diseases, a prerequisite of which is the successful delivery of polynucleic acids (e.g., DNA, RNA) to a patient’s cells. Delivery can be achieved technologically (e.g., using electroporation), using viruses (natural gene delivery vectors) or non-viral vectors (e.g., lipids, nanoparticles, polymers). This article aims to give the reader an overview of the use of organic electronic materials (i.e., fullerenes, graphenes and conjugated polymers) as non-viral gene delivery vectors.