Thermoresponsive in situ forming and self-healing double-network hydrogels as injectable dressings for silymarin/levofloxacin delivery for treatment of third-degree burn wounds.

Our study aimed to introduce a novel double-cross-linked and thermoresponsive hydrogel with remarkable potential for accelerating third-degree burn wound healing. Burn injuries are recognized as challenging, critical wounds. Especially in third-degree burns, treatment is demanding due to extended wounds, irregular shapes, significant exudation, and intense pain during dressing changes. In this work, hydrogels made of zwitterionic chitosan and dialdehyde starch (ZCS and ZDAS) were created to deliver silymarine (SM) and levofloxacin (LEV). The hydrogels were effortlessly produced using dynamic Schiff base linkages and ionic interactions between ZCS and ZDAS at appropriate times. The pore uniformity, gel fraction, and commendable swelling properties can imply a suitable degree of Schiff base cross-link. The hydrogel demonstrated outstanding shape retention, and significant self-healing and flexibility abilities, enabling it to uphold its form even during bodily movements. After injecting biocompatible hydrogel on the wound, a notable acceleration in wound closure was observed on day 21 (98.1 ± 1.10 %) compared to the control group (75.1 ± 6.13 %), and histopathological analysis revealed a reduction of inflammation that can be linked to remarkable antioxidant and antibiotic properties. The results demonstrate the hydrogel's efficacy in promoting burn wound healing, making it a promising candidate for medical applications.

Precise Engineering of Growth Factor Presentation Using Extracellular Microenvironment-Mimicking Microfluidic Microparticles.

One of the main challenges in tissue engineering is finding a way to deliver specific growth factors (GFs) with precise spatiotemporal control over their presentation. Here, we report a novel strategy for generating microscale carriers with enhanced affinity for high content loading suitable for the sustained and localized delivery of GFs. Our developed microparticles can be injected locally and sustainably release encapsulated growth factors for up to 28 days. Fine-tuning of particles' size, affinity, microstructures, and release kinetics is achieved using a microfluidic system along with bioconjugation techniques. We also describe an innovative 3D micromixer platform to control the formation of core-shell particles based on superaffinity using a polymer-peptide conjugate for further tuning of release kinetics and delayed degradation. Chitosan shells block the burst release of encapsulated GFs and enable their sustained delivery for up to 10 days. The matched release profiles and degradation provide the local tissues with biomimetic, developmental-biologic-compatible signals to maximize regenerative effects. The versatility of this approach is verified using three different therapeutic proteins, including human bone morphogenetic protein-2 (rhBMP-2), vascular endothelial growth factor (VEGF), and stromal cell-derived factor 1 (SDF-1α). As in vivo morphogenesis is typically driven by the combined action of several growth factors, the proposed technique can be developed to generate a library of GF-loaded particles with designated release profiles.

Botulinum toxin A dissolving microneedles for hyperhidrosis treatment: design, formulation and in vivo evaluation.

Multiple periodic injections of botulinum toxin A (BTX-A) are the standard treatment of hyperhidrosis which causes excessive sweating. However, BTX-A injections can create problems, including incorrect and painful injections, the risk of drug entry into the bloodstream, the need for medical expertise, and waste disposal problems. New drug delivery systems can substantially reduce these problems. Transdermal delivery is an effective alternative to conventional BTX-A injections. However, BTX-A's large molecular size and susceptibility to degradation complicate transdermal delivery. Dissolving microneedle patches (DMNPs) encapsulated with BTX-A (BTX-A/DMNPs) are a promising solution that can penetrate the dermis painlessly and provide localized translocation of BTX-A. In this study, using high-precision 3D laser lithography and subsequent molding, DMNPs were prepared based on a combination of biocompatible polyvinylpyrrolidone and hyaluronic acid polymers to deliver BTX-A with ultra-sharp needle tips of 1.5 ± 0.5 µm. Mechanical, morphological and histological assessments of the prepared DMNPs were performed to optimize their physicochemical properties. Furthermore, the BTX-A release and diffusion kinetics across the skin layers were investigated. A COMSOL simulation was conducted to study the diffusion process. The primary stability analysis reported significant stability for three months. Finally, the functionality of the BTX-A/DMNPs for the suppression of sweat glands was confirmed on the hyperhidrosis mouse footpad, which drastically reduced sweat gland activity. The results demonstrate that these engineered DMNPs can be an effective, painless, inexpensive alternative to hypodermic injections when treating hyperhidrosis.

Recent progress in PLGA-based microneedle-mediated transdermal drug and vaccine delivery.

Microneedles (MNs) have recently been found to have applications in drug, vitamin, protein and vaccine delivery. Polymeric MN arrays continue to attract increasing attention due to their capability to bypass the skin's stratum corneum (SC) barrier with minimal invasiveness. These carriers can achieve the targeted intradermal delivery of drugs and vaccines and improve their transdermal delivery level. As a nontoxic FDA-approved copolymer, polylactic glycolic acid (PLGA) has good biocompatibility and biodegradability. Currently, PLGA-based MNs have a noticeable tendency to be utilized as a delivery system. This study focuses on the most recent advances in PLGA-based MNs. Both PLGA nanoparticle-based MNs and PLGA matrix-based MNs, created for the delivery of vaccines, drugs, proteins and other therapeutic agents, are discussed. The paper also discusses the various types of MNs and their potential applications. Finally, the prospects and challenges of PLGA-based MNs are reviewed.

Long-Term Vaccine Delivery and Immunological Responses Using Biodegradable Polymer-Based Carriers.

Biodegradable polymers are largely employed in the biomedical field, ranging from tissue regeneration to drug/vaccine delivery. The biodegradable polymers are highly biocompatible and possess negligible toxicity. In addition, biomaterial-based vaccines possess adjuvant properties, thereby enhancing immune responses. This Review introduces the use of different biodegradable polymers and their degradation mechanism. Different kinds of vaccines, as well as the interaction between the carriers with the immune system, then are highlighted. Natural and synthetic biodegradable micro-/nanoplatforms, hydrogels, and scaffolds for local or targeted and controlled vaccine release are subsequently discussed.

In situ bone tissue engineering using gene delivery nanocomplexes.

Gene delivery offers promising outcomes for functional recovery or regeneration of lost tissues at cellular and tissue levels. However, more efficient carriers are needed to safely and locally delivery of genetic materials. Herein, we demonstrate microfluidic-assisted synthesis of plasmid DNA (pDNA)-based nanocomplexe (NC) platforms for bone tissue regeneration. pDNA encoding human bone morphogenesis protein-2 (BMP-2) was used as a gene of interest. Formation and fine-tuning of nanocomplexes (NCs) between pDNA and chitosan (CS) as carriers were performed using a micromixer platform. Flow characteristics were adjusted to tune mixing time and consequently size, zeta potential, and compactness of assembled NCs. Subsequently, NCs were immobilized on a nanofibrous Poly(ε-caprolactone) (PCL) scaffold functionalized with metalloprotease-sensitive peptide (MMP-sensitive). This construct can provide an environmental-sensitive and localized gene delivery platform. Osteogenic differentiation of bone marrow-derived mesenchymal stem cells (MSCs) was studied using chemical and biological assays. The presented results converge to indicate a great potential of the developed methodology for in situ bone tissue engineering using immobilized microfluidic-synthesized gene delivery nanocomplexes, which is readily expandable in the field of regenerative nanomedicine. STATEMENT OF SIGNIFICANCE: In this study, we demonstrate microfluidic-assisted synthesis of plasmid DNA (pDNA)-based nanocomplexes (NCs) platforms for bone tissue regeneration. We used pDNA encoding human bone morphogenesis protein-2 (BMP-2) as the gene of interest. Using micromixer platform nanocomplexes (NCs) between pDNA and chitosan (CS) were fabricated and optimized. NCs were immobilized on a nanofibrous polycaprolactone scaffold functionalized with metalloprotease-sensitive peptide. In vitro and in vivo assays confirmed the osteogenic differentiation of mesenchymal stem cells (MSCs). The obtained data indicated great potential of the developed methodology for in situ bone tissue engineering using immobilized microfluidic-synthesized gene delivery nanocomplexes, which is readily expandable in the field of regenerative nanomedicine.