Harnessing the physicochemical properties of DNA as a multifunctional biomaterial for biomedical and other applications

The biological purpose of DNA is to store, replicate, and convey genetic information in cells. Progress in molecular genetics have led to its widespread applications in gene editing, gene therapy, and forensic science. However, in addition to its role as a genetic material, DNA has also emerged as a nongenetic, generic material for diverse biomedical applications. DNA is essentially a natural biopolymer that can be precisely programed by simple chemical modifications to construct materials with desired mechanical, biological, and structural properties. This review critically deciphers the chemical tools and strategies that are currently being employed to harness the nongenetic functions of DNA. Here, the primary product of interest has been crosslinked, hydrated polymers, or hydrogels. State-of-the-art applications of macroscopic, DNA-based hydrogels in the fields of environment, electrochemistry, biologics delivery, and regenerative therapy have been extensively reviewed. Additionally, the review encompasses the status of DNA as a clinically and commercially viable material and provides insight into future possibilities

Leveraging the advancements in functional biomaterials and scaffold fabrication technologies for chronic wound healing applications

Exploring new avenues for clinical management of chronic wounds holds the key to eliminating socioeconomic burdens and health-related concerns associated with this silent killer. Engineered biomaterials offer great promise for repair and regeneration of chronic wounds because of their ability to deliver therapeutics, protect the wound environment, and support the skin matrices to facilitate tissue growth. This mini review presents recent advances in biomaterial functionalities for enhancing wound healing and demonstrates a move from sub-optimal methods to multi-functionalized treatment approaches. In this context, we discuss the recently reported biomaterial characteristics such as bioadhesiveness, antimicrobial properties, proangiogenic attributes, and anti-inflammatory properties that promote chronic wound healing. In addition, we highlight the necessary mechanical and mass transport properties of such biomaterials. Then, we discuss the characteristic properties of various biomaterial templates, including hydrogels, cryogels, nanomaterials, and biomolecule-functionalized materials. These biomaterials can be microfabricated into various structures, including smart patches, microneedles, electrospun scaffolds, and 3D-bioprinted structures, to advance the field of biomaterial scaffolds for effective wound healing. Finally, we provide an outlook on the future while emphasizing the need for their detailed functional behaviour and inflammatory response studies in a complex in vivo environment for superior clinical outcomes and reduced regulatory hurdles

Investigation of Cell Derived Nanoparticles for Drug Delivery and Osteogenic Differentiation of Human Stem/Stromal Cells

The successful repair of bone defects and injuries is enhanced by the delivery of osteoinductive factors, such as drugs, growth factors, and genetic material that can promote the osteogenic differentiation of stem/stromal cells into osteoblasts. Nanoparticle delivery systems are being studied to enable the sustained release of these factors but suffer from limitations such as cytotoxicity issues, poor loading capacity, and poor cellular uptake. In this project, we developed cell-derived nanoparticles (CDNs), a biomimetic nanoparticle delivery system with high drug loading efficiency, to deliver a glucocorticoid drug, dexamethasone (Dex), to promote the osteogenic differentiation of stem/stromal cells. The synthesized Dex-loaded CDNs had a consistent size range of 30-920 nm, spherical shape, high drug loading efficiency, good cytocompatibility, and were internalized by human adipose-derived stem/stromal cells (hADSCs). Drug-loaded CDNs were able to induce the osteogenic differentiation of hADSCs in vitro, indicating their potential as an efficient drug delivery vehicle for bone regeneration and other applications

Exploiting the role of nanoparticles for use in hydrogel-based bioprinting applications: concept, design, and recent advances

Three-dimensional (3D) bioprinting is an emerging tissue engineering approach that aims to develop cell or biomolecule-laden, complex polymeric scaffolds with high precision, using hydrogel-based “bioinks”. Hydrogels are water-swollen, highly crosslinked polymer networks that are soft, quasi-solid, and can support and protect biological materials. However, traditional hydrogels have weak mechanical properties and cannot retain complex structures. They must be reinforced with physical and chemical manipulations to produce a mechanically resilient bioink. Over the past few years, we have witnessed an increased use of nanoparticles and biological moiety-functionalized nanoparticles to fabricate new bioinks. Nanoparticles of varied size, shape, and surface chemistries can provide a unique solution to this problem primarily because of three reasons: (a) nanoparticles can mechanically reinforce hydrogels through physical and chemical interactions. This can favorably influence the bioink\u27s 3D printability and structural integrity by modulating its rheological, biomechanical, and biochemical properties, allowing greater flexibility to print a wide range of structures; (b) nanoparticles can introduce new bio-functionalities to the hydrogels, which is a key metric of a bioink\u27s performance, influencing both cell–material and cell–cell interactions within the hydrogel; (c) nanoparticles can impart “smart” features to the bioink, making the tissue constructs responsive to external stimuli. Responsiveness of the hydrogel to magnetic field, electric field, pH changes, and near-infrared light can be made possible by the incorporation of nanoparticles. Additionally, bioink polymeric networks with nanoparticles can undergo advanced chemical crosslinking, allowing greater flexibility to print structures with varied biomechanical properties. Taken together, the unique properties of various nanoparticles can help bioprint intricate constructs, bringing the process one step closer to complex tissue structure and organ printing. In this review, we explore the design principles and multifunctional properties of various nanomaterials and nanocomposite hydrogels for potential, primarily extrusion-based bioprinting applications. We illustrate the significance of biocompatibility of the designed nanocomposite hydrogel-based bioink for clinical translation and discuss the different parameters that affect cell fate after cell-nanomaterial interaction. Finally, we critically assess the current challenges of nanoengineering bioinks and provide insight into the future directions of potential hydrogel bioinks in the rapidly evolving field of bioprinting

Engineering nanoparticle therapeutics for impaired wound healing in diabetes.

Diabetes mellitus is a chronic disease characterized by increased blood glucose levels, leading to damage of the nerves blood vessels, subsequently manifesting as organ failures, wounds, or ulcerations. Wounds in patients with diabetes are further complicated because of reduced cytokine responses, infection, poor vascularization, and delayed healing processes. Surface-functionalized and bioengineered nanoparticles (NPs) have recently gained attention as emerging treatment modalities for wound healing in diabetes. Here, we review emerging therapeutic NPs to treat diabetic wounds and highlight their discrete delivery mechanisms and sites of action. We further critically assess the current challenges of these nanoengineered materials for successful clinical translation and discuss their potential for growth in the clinical marketplace

Systematic review of newer agents for the management of alopecia areata in adults: Janus kinase inhibitors, biologics and phosphodiesterase-4 inhibitors

Management options for moderate-to-severe alopecia areata (AA) are limited owing to a lack of safe and effective treatments suitable for long-term use. However, newer agents have the potential to induce and maintain hair regrowth in patients with a better side-effects profile compared to systemic steroids or conventional systemic agents. In this article, we conducted a systematic review of newer agents, including Janus kinase (JAK) inhibitors, biologics and phosphodiesterase-4 (PDE-4) inhibitors, for the treatment of AA in adult patients evaluated in randomized controlled trials (RCTs) using the Severity of Alopecia Tool score. A literature search was performed on PubMed and ClinicalTrials.gov, which identified 106 items with 12 RCTs eligible for review. Information regarding the treatment regimen, duration, endpoints, efficacy and adverse events were extracted; product monograph information was also summarized for approved agents with or without indications for AA. Overall, current data suggest the oral JAK inhibitors (baricitinib, ritlecitinib, deuruxolitinib, brepocitinib) as a promising new class of agents that can induce significant hair regrowth, with mild to moderate adverse effects. Baricitinib recently received US FDA approval for the treatment of severe AA, while ritlecitinib and deuruxolitinib have received the breakthrough therapy designation for AA. In contrast, PDE-4 inhibitors (apremilast) and the biologics (dupilumab, secukinumab and aldesleukin) appear to have limited efficacy thus far. Results from ongoing and future long-term studies could shed light on the utility of the newer agents in altering the progression of AA

Systematic review of mesotherapy: a novel avenue for the treatment of hair loss

Mesotherapy is a technique by which lower doses of therapeutic agents and bioactive substances are administered by intradermal injections to the skin. Through intradermal injections, mesotherapy can increase the residence time of therapeutic agents in the affected area, thus allowing for the use of lower doses and longer intervals between sessions which may in turn improve the treatment outcome and patient compliance. This systematic review aims to summarize the current literature that evaluates the efficacy of this technique for the treatment of hair loss and provides an overview of the results observed. Of the 416 records identified, 27 articles met the inclusion criteria. To date, mesotherapy using 6 classes of agents and their combinations have been studied; this includes dutasteride, minoxidil, growth factors or autologous suspension, botulinum toxin A, stem cells, and mesh solutions/multivitamins. While several studies report statistically significant improvements in hair growth after treatment, there is currently a lack of standardized regimens. The emergence of adverse effects after mesotherapy has been reported. Further large-scale and controlled clinical trials are warranted to evaluate the utility of mesotherapy for hair loss disorders