Drug conjugates crosslinked bioresponsive hydrogel for combination therapy of diabetic wound.

Basic fibroblast growth factor (bFGF) has proved to be effective for wound healing, yet its effectiveness is extremely retarded in diabetic wounds due to the severe oxidative stress in wound beds. To solve this issue, herein a novel combination therapy of bFGF and N-acetylcysteine (NAC, antioxidant) was devised for improved diabetic wound repair. To avoid rapid loss of both drugs in the wound beds, a bioresponsive hydrogel (bFGF-HSPP-NAC) was engineered by incorporating bFGF and NAC into polymer-drug conjugates (HSPP) via thiol-disulfide exchange reactions.

Bio-inspired aFGF modification functionalized piezoelectric chitosan films for promoting scald wound healing.

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.

Tissue-Adaptive BSA Hydrogel with Dual Release of PTX and bFGF Promotes Spinal Cord Injury Repair via Glial Scar Inhibition and Axon Regeneration.

Spinal cord injury (SCI) is a severe clinical disease usually accompanied by activated glial scar, neuronal axon rupture, and disabled motor function. To mimic the microenvironment of the SCI injury site, a hydrogel system with a comparable mechanical property to the spinal cord is desirable. Therefore, a novel elastic bovine serum albumin (BSA) hydrogel is fabricated with excellent adhesive, injectable, and biocompatible properties.

Liposomal nano-encapsulation of bFGF combined with injectable BSA hydrogel for efficient burn wound healing.

Rapid and scar-free healing of burn wounds is an urgent clinical issue. Basic fibroblast growth factor (bFGF) has been proven to promote the healing of burn wounds by accelerating ECM remodeling and angiogenesis. However, exudates from burn wounds can accelerate bFGF degradation, thereby affecting its bioactivity.

Microneedle Patch for Transdermal Sequential Delivery of KGF-2 and aFGF to Enhance Burn Wound Therapy.

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.

Biomaterial-Based Sustained-Release Drug Formulations for Localized Cancer Immunotherapy.

Cancer immunotherapy has revolutionized clinical cancer treatments by taking advantage of the immune system to selectively and effectively target and kill cancer cells. However, clinical cancer immunotherapy treatments often have limited efficacy and/or present severe adverse effects associated primarily with their systemic administration. Localized immunotherapy has emerged to overcome these limitations by directly targeting accessible tumors via local administration, reducing potential systemic drug distribution that hampers drug efficacy and safety.

Drug cross-linking electrospun fiber for effective infected wound healing.

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).

Adhesive, injectable, and ROS-responsive hybrid polyvinyl alcohol (PVA) hydrogel co-delivers metformin and fibroblast growth factor 21 (FGF21) for enhanced diabetic wound repair.

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 results proved that the hydrogel was adhesive and injectable, and that it could particularly scavenge reactive oxygen species (ROSs), while the data demonstrated that the hydrogel could promote angiogenesis by recruiting endothelial progenitor cells (EPCs) through upregulation of Ang-1.

Advances for the treatment of lower extremity arterial disease associated with diabetes mellitus.

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.

Latest on biomaterial-based therapies for topical treatment of psoriasis.

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.

Methacrylated gelatin shape-memorable cryogel subcutaneously delivers EPCs and aFGF for improved pressure ulcer repair in diabetic rat model.

Pressure ulcer (PU) in patients with diabetes mellitus (DM) is still a clinical intractable issue due to the complicated physiological characteristics by the prolonged high glucose level and impaired angiogenesis. The PU treatment includes surgical debridement, stem cell therapy and growth factors, leading to high cost and repeated professional involvement. Developing effective wound dressing combining the therapeutic cells and growth factors has become highly demanded.

A General Protein Unfolding-Chemical Coupling Strategy for Pure Protein Hydrogels with Mechanically Strong and Multifunctional Properties.

Protein-based hydrogels have attracted great attention due to their excellent biocompatible properties, but often suffer from weak mechanical strength. Conventional strengthening strategies for protein-based hydrogels are to introduce nanoparticles or synthetic polymers for improving their mechanical strength, but often compromise their biocompatibility. Here, a new, general, protein unfolding-chemical coupling (PNC) strategy is developed to fabricate pure protein hydrogels without any additives to achieve both high mechanical strength and excellent cell biocompatibility.

Zwitterionic Hydrogel Activates Autophagy to Promote Extracellular Matrix Remodeling for Improved Pressure Ulcer Healing.

Pressure ulcer (PU) is a worldwide problem that is hard to heal because of its prolonged inflammatory response and impaired ECM deposition caused by local hypoxia and repeated ischemia/reperfusion. Our previous study discovered that the non-fouling zwitterionic sulfated poly (sulfobetaine methacrylate) (SBMA) hydrogel can improve PU healing with rapid ECM rebuilding. However, the mechanism of the SBMA hydrogel in promoting ECM rebuilding is unclear.

Advances of Microneedles in Biomedical Applications.

A microneedle (MN) is a painless and minimally invasive drug delivery device initially developed in 1976. As microneedle technology evolves, microneedles with different shapes (cone and pyramid) and forms (solid, drug-coated, hollow, dissolvable and hydrogel-based microneedles) have been developed. The main objective of this review is the applications of microneedles in biomedical areas.

PRMT7 targets of Foxm1 controls alveolar myofibroblast proliferation and differentiation during alveologenesis.

Although aberrant alveolar myofibroblasts (AMYFs) proliferation and differentiation are often associated with abnormal lung development and diseases, such as bronchopulmonary dysplasia (BPD), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF), epigenetic mechanisms regulating proliferation and differentiation of AMYFs remain poorly understood. Protein arginine methyltransferase 7 (PRMT7) is the only reported type III enzyme responsible for monomethylation of arginine residue on both histone and nonhistone substrates. Here we provide evidence for PRMT7's function in regulating AMYFs proliferation and differentiation during lung alveologenesis.

Antimicrobial α-defensins as multi-target inhibitors against amyloid formation and microbial infection.

Amyloid aggregation and microbial infection are considered as pathological risk factors for developing amyloid diseases, including Alzheimer's disease (AD), type II diabetes (T2D), Parkinson's disease (PD), and medullary thyroid carcinoma (MTC). Due to the multifactorial nature of amyloid diseases, single-target drugs and treatments have mostly failed to inhibit amyloid aggregation and microbial infection simultaneously, thus leading to marginal benefits for amyloid inhibition and medical treatments. Herein, we proposed and demonstrated a new "anti-amyloid and antimicrobial hypothesis" to discover two host-defense antimicrobial peptides of α-defensins containing β-rich structures (human neutrophil peptide of HNP-1 and rabbit neutrophil peptide of NP-3A), which have demonstrated multi-target, sequence-independent functions to (i) prevent the aggregation and misfolding of different amyloid proteins of amyloid-β (Aβ, associated with AD), human islet amyloid polypeptide (hIAPP, associated with T2D), and human calcitonin (hCT, associated with MTC) at sub-stoichiometric concentrations, (ii) reduce amyloid-induced cell toxicity, and (iii) retain their original antimicrobial activity upon the formation of complexes with amyloid peptides.

Mussel-Inspired Surface Immobilization of Heparin on Magnetic Nanoparticles for Enhanced Wound Repair via Sustained Release of a Growth Factor and M2 Macrophage Polarization.

Efficient reconstruction of a fully functional skin after wounds requires multiple functionalities of wound dressing due to the complexity of healing. In these regards, topical administration of functionalized nanoparticles capable of sustainably releasing bioactive agents to the wound site may significantly accelerate wound repair. Among the various nanoparticles, superparamagnetic iron oxide (FeO) nanoparticles gain increasing attractiveness due to their intrinsic response to an external magnetic field (eMF).

Freeze-Thawing Chitosan/Ions Hydrogel Coated Gauzes Releasing Multiple Metal Ions on Demand for Improved Infected Wound Healing.

Imbalance of metal ions in the wound microenvironment is a key factor that leads to delayed wound healing. However, single metal administration to enhance wound repair is usually not enough due to the overlapping nature of the wound healing phases. Herein, a facile freeze-thawing strategy is developed to incorporate chitosan/ions hydrogel into medical gauzes to realize on-demand release of multiple ions to accelerate wound healing.

Zwitterionic hydrogel for sustained release of growth factors to enhance wound healing.

Growth factors (GFs) have been well known for their therapeutic effects on wound healing. Due to their vulnerable biostability, biomaterial carriers are usually used to deliver GFs to maintain their bioactivity. Among the carriers, PEG hydrogels are the most widely applied.

Molecular Dynamics Simulations of Cholesterol Effects on the Interaction of hIAPP with Lipid Bilayer.

Fundamental understanding of specific interactions of human islet amyloid polypeptide (hIAPP) with cell membrane is critical for elucidating the underlying pathogenesis of type II diabetes mellitus (T2DM). Membrane cholesterol is known to regulate membrane functions and properties, but its exact role in driving hIAPP-membrane interactions still remains controversial. In this work, we computationally investigated the concentration effect of cholesterol on the adsorption, orientation, and surface interaction of hIAPP oligomers on POPC bilayers containing different amounts of cholesterol (χ = 0, 20, and 40 mol %).

Highly Water-Preserving Zwitterionic Betaine-Incorporated Collagen Sponges With Anti-oxidation and Anti-inflammation for Wound Regeneration.

A core problem in wound healing - with both fundamental and technological significance - concerns the rational design of bioactive and moist microenvironments. Here, we design a new class of zwitterionic betaine-incorporated collagen sponges (BET@COL) with integrated anti-oxidation and anti-inflammatory properties for promoting wound healing in a full-thickness wound model. The presence of zwitterionic betaine in a 3D network structure of collagen enables tightly bound and locked water molecules inside sponges via ionic solvation and confinement effect, while the integration of this amino acid also empowers the sponge with anti-oxidation and anti-inflammatory functions.

Bioactive ECM Mimic Hyaluronic Acid Dressing via Sustained Releasing of bFGF for Enhancing Skin Wound Healing.

Successful dermal wound regeneration requires the coordination of repair cells and cellular signals with the extracellular matrix (ECM), which serves as an indispensable mechanical and biological supporter for cell functions and communications with varied cytokines during healing processes. Here, we developed an injectable bioactive wound dressing, methacrylated hyaluronic acid (Me-HA)-based hydrogel loading with basic fibroblast growth factor (bFGF), endowing the dressing with the pleiotropic bioactivity to mimic natural ECM. This bFGF@Me-HA dressing was applied to a mouse with full-thickness excisional wounds to investigate its positive roles in wound repair owing to the complementary functions of HA with sustained release of bioactive bFGF.

Zwitterionic poly(sulfobetaine methacrylate) hydrogels with optimal mechanical properties for improving wound healing in vivo.

Zwitterionic hydrogels, as highly hydrated and soft materials, have been considered as promising materials for wound dressing, due to their unique antifouling and mechanical properties. While the viscoelasticity and softness of zwitterionic hydrogels are hypothetically essential for creating adaptive cellular niches, the underlying mechanically regulated wound healing mechanism still remains elusive. To test this hypothesis, we fabricated zwitterionic poly(sulfobetaine methacrylate) (polySBMA) hydrogels with different elastic moduli prepared at different crosslinker contents, and then applied the hydrogels to full-thickness cutaneous wounds in mice.

Highly Aligned Electrospun Collagen/Polycaprolactone Surgical Sutures with Sustained Release of Growth Factors for Wound Regeneration.

Development of biocompatible and bioactive drug-loaded sutures is considered as an effective but challenging strategy for the wound healing process by delivering biological drugs (e.g., antibiotics) or growth factors (e.