The application of acidic fibroblast growth factor (aFGF) has shown great potential in the treatment of scald or burn wounds with high morbidity and mortality, especially in promoting the repair of deep partial-thickness wounds. However, its short half-life and instability in vivo do pose challenges for clinical application. Herein, two kinds of bio-inspired modified piezoelectric chitosan (CS) films, namely heparin-coated CS film (HCS) and polydopamine-coated CS film (DCS), are facially fabricated and adopted as controlled-release platforms for local delivery of aFGF. Polydopamine or heparin layers serve as a bridge grafting on chitosan films, facilitating the loading of aFGF and enabling controlled release of aFGF from the piezoelectric film through intermolecular interactions. Additionally, these layers enhance the hydrophilicity and antibacterial properties of the bare CS film due to their inherent biological activities. Furthermore, the polydopamine coating imparts photothermal activity to the CS film. The in vivo experiments ascertain that the synergetic effect of the controlled-released aFGF and low temperature photothermal therapy collectively accelerate scald wound healing outcomes within 14 days by facilitating granulation formation, collagen deposition, re-epithelialization and angiogenesis. This study opens up new possibilities for the development of multifunctional chitosan-based wound dressings and the creation of innovative drug delivery platforms.

Severe burn wounds usually destroy key cells' functions of the skin resulting in delayed re-epithelization and wound regeneration. Promoting key cells' activities is crucial for burn wound repair. It is well known that keratinocyte growth factor-2 (KGF-2) participates in the proliferation and morphogenesis of epithelial cells while acidic fibroblast growth factor (aFGF) is a key mediator for fibroblast and endothelial cell growth and differentiation. However, thick eschar and the harsh environment of a burn wound often decrease the delivery efficiency of fibroblast growth factor (FGF) to the wound site. Therefore, herein a novel microneedle patch for sequential transdermal delivery of KGF-2 and aFGF is fabricated to enhance burn wound therapy. aFGF is first loaded in the nanoparticle (NPaFGF) and then encapsulated NPaFGF with KGF-2 in the microneedle patch (KGF-2/NPaFGF@MN). The result shows that KGF-2/NPaFGF@MN can successfully get across the eschar and sequentially release KGF-2 and aFGF. Additional data demonstrated that KGF-2/NPaFGF@MN achieved a quicker wound closure rate with reduced necrotic tissues, faster re-epithelialization, enhanced collagen deposition, and increased neo-vascularization. Further evidence suggests that improved wound healing is regulated by significantly elevated expressions of hypoxia-inducible factor-1 alpha (HIF-1ɑ) and heat shock protein 90 (Hsp90) in burn wounds. All these data proved that KGF-2/NPaFGF@MN is an effective treatment for wound healing of burns.

Comprehending the adsorption behavior of pharmaceutical molecules on the surface of fullerene-like nanostructures is fundamental to their applications in medical engineering. Herein, density functional theory (DFT) and quasiclassical molecular dynamics (MD) calculations have been performed to explore the adsorption behavior of pyrazinamide (PZA) on the surface of X12Y12 (X = B, Al; Y = N, P) nanocages so as to screen the promising nanocages. The interaction energy and atoms in molecules (AIM) analysis for the most stable adsorption configuration of PZA showed that there were partially covalent interac-tions, covalent interactions and electrostatic interactions between PZA and B12Y12, Al12N12, Al12P12 nanoc-age, respectively. Upon adsorption, the HOMO-LUMO energy gap (Ebg) for all X12Y12-PZA complexes decreased, with the largest reduction (50.30 %) found in B12N12-PZA complex. The MD simulations of adsorption process indicated the structure of Al12Y12 was destroyed due to the reaction with PZA, while B12Y12 still maintained its cage-like structure. Further analysis of four typical adsorption configurations of PZA on B12N12 confirmed different B12N12-PZA complexes have relatively close Eint, large fluctuations in their HOMO-LUMO energy gap and partially covalent interactions between B12N12 and PZA. All the results suggest that B12N12 nanocage may act as superior sensor and drug delivery candidate for PZA.(c) 2023 Elsevier B.V. All rights reserved.

AAV vector-mediated gene therapy has been proposed as a feasible strategy for several eye diseases. However, AAV antibodies in the serum prior to treatment hinder the transduction efficiency and thus the therapeutic effect. Therefore, it is necessary to evaluate AAV antibodies in the serum before gene therapy. As large animals, goats are more closely related to humans than rodents and more economically available than nonhuman primates. Here, we first evaluated the AAV2 antibody serum level in rhesus monkeys before AAV injection. Then, we optimized a cell-based neutralizing antibody assay for detecting AAV antibodies in the serum of Saanen goats and evaluated the consistency of the cell-based neutralizing antibody assay and ELISA for goat serum antibody evaluation. The cell-based neutralizing antibody assay showed that the percentage of macaques with low antibody levels was 42.86%; however, there were no macaques with low antibody levels when the serum was evaluated by ELISA. The proportion of goats with low antibody levels was 56.67% according to the neutralizing antibody assay and 33. 33% according to the ELISA, and McNemar's test showed that the results of the two assays were not significantly different (P = 0.754), but that their consistency is poor (Kappa = 0.286, P = 0.114). Moreover, longitudinal evaluation of serum antibodies before and after intravitreal injection of AAV2 in goats revealed that the level of AAV antibodies increased and transduction inhibition subsequently increased, as reported in humans, indicating that transduction inhibition should be taken into account at different stages of gene therapy. In summary, starting with an evaluation of monkey serum antibodies, we optimized a detection method of goat serum antibodies, providing an alternative large animal model for gene therapy, and our serum antibody measurement method may be applied to other large animals.

Abstract The management of infected wounds is still an intractable challenge in clinic. Development of antibacterial wound dressing is of great practical significance for wound management. Herein, a natural‐derived antibacterial drug, tannic acid (TA), was incorporated into the electrospun polyvinyl alcohol (PVA) fiber (TA/PVA fiber, 952 ± 40 nm in diameter). TA worked as a cross‐linker via hydrogen bonding with PVA to improve the physicochemical properties of the fiber and to reach a sustained drug release (88% release of drug at 48 h). Improved mechanical property (0.8–1.2 MPa) and computational simulation validated the formation of the hydrogen bonds between TA and PVA. Moreover, the antibacterial and anti‐inflammatory characteristics of TA laid the foundation for the application of TA/PVA fiber in repairing infected wounds. Meanwhile, in vitro studies proved the high hemocompatibility and cytocompatibility of TA/PVA fiber. Further in vivo animal investigation showed that the TA/PVA fiber promoted the repair of infected wound by inhibiting the bacterial growth, promoting granulation formation, and collagen matrix deposition, accelerating angiogenesis, and inducing M2 macrophage polarization within 14 days. All the data demonstrated that the TA cross‐linked fiber would be a potent dressing for bacteria‐infected wound healing.

Lower extremity arterial disease (LEAD) is a major vascular complication of diabetes. Vascular endothelial cells dysfunction can exacerbate local ischemia, leading to a significant increase in amputation, disability, and even mortality in patients with diabetes combined with LEAD. Therefore, it is of great clinical importance to explore proper and effective treatments. Conventional treatments of diabetic LEAD include lifestyle management, medication, open surgery, endovascular treatment, and amputation. As interdisciplinary research emerges, regenerative medicine strategies have provided new insights to treat chronic limb threatening ischemia (CLTI). Therapeutic angiogenesis strategies, such as delivering growth factors, stem cells, drugs to ischemic tissues, have also been proposed to treat LEAD by fundamentally stimulating multidimensional vascular regeneration. Recent years have seen the rapid growth of tissue engineering technology; tissue-engineered biomaterials have been used to study the treatment of LEAD, such as encapsulation of growth factors and drugs in hydrogel to facilitate the restoration of blood perfusion in ischemic tissues of animals. The primary purpose of this review is to introduce treatments and novel biomaterials development in LEAD. Firstly, the pathogenesis of LEAD is briefly described. Secondly, conventional therapies and therapeutic angiogenesis strategies of LEAD are discussed. Finally, recent research advances and future perspectives on biomaterials in LEAD are proposed.

Psoriasis is an autoimmune inflammatory disease which is fundamentally different from dermatitis. Its treatments include topical medications and systemic drugs depending on different stages of the disease. However, these commonly used therapies are falling far short of clinical needs due to various drawbacks. More precise therapeutic strategies with minimized side effects and improved compliance are highly demanded. Recently, the rapid development of biomaterial-based therapies has made it possible and promising to attain topical psoriasis treatment. In this review, we briefly describe the significance and challenges of the topical treatment of psoriasis and emphatically overview the latest progress in novel biomaterial-based topical therapies for psoriasis including microneedles, nanoparticles, nanofibers, and hydrogels. Current clinical trials related to each biomaterial are also summarized and discussed.

As conventional treatments for diabetic wounds often fail to achieve rapid satisfactory healing, the development of effective strategies to accelerate diabetic wound repair is highly demanded. Herein, fibroblast growth factor 21 (FGF21) and metformin co-loaded multifunctional polyvinyl alcohol (PVA) hydrogel were fabricated for improved diabetic wound healing. The in vitro results proved that the hydrogel was adhesive and injectable, and that it could particularly scavenge reactive oxygen species (ROSs), while the in vivo data demonstrated that the hydrogel could promote angiogenesis by recruiting endothelial progenitor cells (EPCs) through upregulation of Ang-1. Both ROSs' removal and EPCs' recruitment finally resulted in enhanced diabetic wound healing. This work opens a strategy approach to diabetic wound management by combining biological macromolecules and small chemical molecules together using one promising environmental modulating drug delivery system.