Eugenol-loaded polyurethane gelatin dressing for efficient angiogenesis and antibacterial effects in refractory diabetic wound defect healing.

The amelioration of refractory diabetic ulcers presents a formidable conundrum on a global scale, attributable to the elevated peril of contagion and protracted convalescence durations. Within the purlieus of this reparative epoch, the deployment of efficacious wound coverings endowed with both angiogenesis and antibacterial attributes is of paramount significance. Hydrogel wound dressings are distinguished by their elevated biocompatibility, adhesive tenacity, and innate regenerative capacity. Eugenol, a substance distilled from the blossoms of the lilac, serves as a precursor to metformin and is known to impede the genesis of reactive oxygen species. Although its antibacterial effects have been extensively chronicled, the angiogenic ramifications of eugenol within the context of wound remediation remain under-investigated. This research aimed to evaluate the effectiveness of eugenol-infused hydrogel as a wound dressing material. In this context, polyurethane gelatin (PG) was combined with eugenol at concentrations of 0.5% and 1%, creating PG-eugenol hydrogel mixtures with specific mass ratios for both in vivo and in vitro assessments. The in vivo studies indicated that hydrogels infused with eugenol expedited diabetic wound healing by fostering angiogenesis. Enhanced healing was noted, attributed to improved antibacterial and angiogenic properties, increased cell proliferation, tissue regeneration, and re-epithelialization. The in vitro analyses revealed that eugenol-enriched hydrogels stimulated the growth of fibroblasts (HFF-1) and human umbilical vein endothelial cells (HUVECs) and exhibited antibacterial characteristics. This investigation confirms the potential of eugenol-laden hydrogels in effectively treating diabetic wound defects.

Engineering of a NIR-activable hydrogel-coated mesoporous bioactive glass scaffold with dual-mode parathyroid hormone derivative release property for angiogenesis and bone regeneration.

Osteogenesis, osteoclastogenesis, and angiogenesis play crucial roles in bone regeneration. Parathyroid hormone (PTH), an FDA-approved drug with pro-osteogenic, pro-osteoclastogenic and proangiogenic capabilities, has been employed for clinical osteoporosis treatment through systemic intermittent administration. However, the successful application of PTH for local bone defect repair generally requires the incorporation and delivery by appropriate carriers. Though several scaffolds have been developed to deliver PTH, they suffer from the weaknesses such as uncontrollable PTH release, insufficient porous structure and low mechanical strength. Herein, a novel kind of NIR-activable scaffold (CBP/MBGS/PTHrP-2) with dual-mode PTHrP-2 (a PTH derivative) release capability is developed to synergistically promote osteogenesis and angiogenesis for high-efficacy bone regeneration, which is fabricated by integrating the PTHrP-2-loaded hierarchically mesoporous bioactive glass (MBG) into the N-hydroxymethylacrylamide-modified, photothermal agent-doped, poly(N-isopropylacrylamide)-based thermosensitive hydrogels through assembly process. Upon on/off NIR irradiation, the thermoresponsive hydrogel gating undergoes a reversible phase transition to allow the precise control of on-demand pulsatile and long-term slow release of PTHrP-2 from MBG mesopores. Such NIR-activated dual-mode delivery of PTHrP-2 by this scaffold enables a well-maintained PTHrP-2 concentration at the bone defect sites to continually stimulate vascularization and promote osteoblasts to facilitate and accelerate bone remodeling. In vivo experiments confirm the significant improvement of bone reparative effect on critical-size femoral defects of rats. This work paves an avenue for the development of novel dual-mode delivery systems for effective bone regeneration.

Bacterial cellulose-based hydrogel with antibacterial activity and vascularization for wound healing.

Skin wounds need an appropriate wound dressing to help prevent bacterial infection and accelerate wound closure. Bacterial cellulose (BC) with a three-dimensional (3D) network structure is an important commercial dressing. However, how to effectively load antibacterial agents and balance the antibacterial activity is a lingering issue. Herein, this study aims to develop a functional BC hydrogel containing silver-loaded zeolitic imidazolate framework-8 (ZIF-8) antibacterial agent. The tensile strength of the prepared biopolymer dressing is >1 MPa, the swelling property is over 3000 %, the temperature can reach 50 °C in 5 min with near-infrared (NIR) and the release of Ag+ and Zn2+ is stable. In vitro investigation shows that the hydrogel displays enhanced antibacterial activity, and the bacteria survival ratios are only 0.85 % and 0.39 % against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In vitro cell experiments present that BC/polydopamine/ZIF-8/Ag (BC/PDA/ZIF-8/Ag) shows satisfactory biocompatibility and promising angiogenic ability. In vivo study, the full-thickness skin defect on rats demonstrates remarkably wound healing ability and accelerated skin re-epithelialization. This work presents a competitive functional dressing with effective antibacterial properties and accelerative angiogenesis activities for wound repair.

Zn2+-Loaded adhesive bacterial cellulose hydrogel with angiogenic and antibacterial abilities for accelerating wound healing.

Background: Wound healing is a process that requires angiogenesis and antibacterial activities and it remains a challenge for both experimental and clinical research worldwide. Zn2+ has been reported to be widely involved in angiogenesis and exerts antibacterial effects, making it suitable as a treatment to promote wound healing. Therefore Zn2+-loaded adhesive bacterial cellulose hydrogel was designed to observe its angiogenic and antibacterial abilities in the wound healing process. Methods: The characterization, tensile strength, swelling behaviors and antibacterial activity of bacterial cellulose/polydopamine/zeolitic imidazolate framework-8 (BC/PDA/ZIF8) hydrogels were tested. Cell-Counting-Kit-8 (CCK8), transwell, tube formation and real time qunantitative PCR (qRT-PCR) assays were performed to evaluate the cell compatibility of BC/PDA/ZIF8 hydrogels in vitro. A full-thickness defect wound model and histological assays were used to evaluate the BC/PDA/ZIF8 hydrogels in vivo. Results: The prepared BC/PDA/ZIF8 hydrogels exhibited suitable mechanical strength, excellent swelling properties, good tissue adhesion, efficient angiogenic and antibacterial effects and good performance as a physical barrier. In vivo experiments showed that the BC/PDA/ZIF8 hydrogels accelerated wound healing in a full-thickness defect wound model by stimulating angiogenesis. Conclusions: This study proved that BC/PDA/ZIF8 hydrogels possess great potential for promoting satisfactory wound healing in full-thickness wound defects through antibacterial effects and improved cell proliferation, tissue formation, remodeling and re-epithelialization.

Efficient angiogenesis-based wound healing through hydrogel dressing with extracellular vesicles release.

Wound healing and angiogenesis remain challenges for both clinical and experimental research worldwide. Periosteum-derived extracellular vesicles (P-sEVs) delivered by hydrogel dressings provide a potential strategy for wound defects to promote fast healing. In this study, we designed a NAGA/GelMA/Laponite/glycerol hydrogel wound dressing that can release P-sEVs to accelerate angiogenesis and wound healing (named P-sEVs@hydrogel) (N-acryloyl glycinamide, NAGA). The wound dressing showed multiple functions, including efficient angiogenesis, tissue adhesion and a physical barrier. P-sEVs significantly enhanced the proliferation, migration, and tube formation of endothelial cells in vitro. The results of in vivo experiments showed that P-sEVs@hydrogel accelerates the healing of a full-thickness defect wound model by stimulating the angiogenic process. The improved cell proliferation, tissue formation, remodeling, and re-epithelialization possibly resulted in the fast healing. This study shows that multifunctional hydrogel dressing combined with bioactive molecules can achieve fast and satisfactory wound healing in full-thickness wound defects and other related wounds.

Tannic Acid-mediated Multifunctional 3D Printed Composite Hydrogel for Osteochondral Regeneration.

Hydrogels have become an attractive option for tissue repair. A novel multifunctional hydrogel was developed using a two-step method involving photopolymerization and tannic acid (TA) solution incubation. The mechanical properties of this hydrogel were enhanced by the multi-hydrogen bond interaction between the TA and N-acryloyl glycinamide/gelatin methacrylate (NAGA/GelMA). The compressive modulus was doubled. The compressive strengths of the hydrogel were 5.5 MPa. The swelling rate was reduced by a factor of three. The adhesion strength of the composite hydrogel reached 80 KPa. The TA-mediated NAGA/GelMA/Laponite composite hydrogel exhibited excellent anti-fatigue and anti-oxidation properties, as well as printability. In vitro experiments indicated that the TA-mediated hydrogel facilitated the proliferation of bone marrow mesenchymal stem cells and osteogenic and chondrogenic differentiation. The developed multifunctional composite hydrogel has great potential for osteochondral defect repair under osteoarthritis conditions.

Loading Mesenchymal Stem Cell-Derived Exosomes Into a Traditionally Designed Rotator Cuff Patch: A Potential Strategy to Enhance the Repair of Chronic Rotator Cuff Tear Associated With Degenerative Changes.

BACKGROUND: Retraction and degenerative changes of chronic rotator cuff tears limit the healing capacity after routine surgical repair. PURPOSE: To fabricate a mesenchymal stem cell-derived exosome (MSC-Exos) loaded patch and evaluate the effect of this patch on the activity of rabbit tenocytes in vitro and on the repair of chronic rotator cuff tears associated with degenerative changes in vivo. STUDY DESIGN: Controlled laboratory study. METHODS: The MSC-Exos loaded patch was fabricated using a dynamic wet-spinning system. In the in vitro studies, the proliferation and migration activities of tenocytes were evaluated by culturing tenocytes with saline, a fiber-aligned patch, or an MSC-Exos loaded patch. In the in vivo studies, a rabbit model of chronic rotator cuff tear was established and directly repaired, repaired with fiber-aligned patch augmentation (RFPA group), and repaired with MSC-Exos loaded patch augmentation (REPA group). Histological and biomechanical analyses were performed at 4, 8, and 12 weeks after surgery. RESULTS: An MSC-Exos loaded patch with inner aligned fibers, a loose microstructure, and reliable initial strength was fabricated using a dynamic wet-spinning system. The MSC-Exos loaded patch significantly promoted tenocyte proliferation and migration activities in vitro. In vivo, the REPA group exhibited significantly higher tendon maturing scores at 8 and 12 weeks after surgery compared with both the control and the RFPA groups. Fatty infiltration was significantly reduced in the REPA group at 4, 8, and 12 weeks compared with both the control and the RFPA groups. Biomechanical properties, including load to failure and stress, were also significantly improved at 12 weeks in the REPA group compared with both the control and the RFPA groups. CONCLUSION: Results in the present study suggested that an MSC-Exos loaded patch was able to enhance the repair of a chronic rotator cuff tear by providing mechanical support and minimizing degeneration. CLINICAL RELEVANCE: This work supported the idea that loading bioactive MSC-Exos into a traditionally designed rotator cuff patch might exert a better effect on the repair of chronic rotator cuff tears than augmented patch repair alone.

Tea polyphenol/glycerol-treated double-network hydrogel with enhanced mechanical stability and anti-drying, antioxidant and antibacterial properties for accelerating wound healing.

Frequent dressing changes can result in secondary wound damage. Therefore, it is of great significance to construct a wound dressing that can be used for a long time without changing. Here, a double-network hydrogel was synthesized through hydrogen bonding interactions of tea polyphenol (TP)/glycerol with photo-crosslinked N-acryloyl glycinamide (NAGA), gelatin methacrylate (GelMA), and nanoclay hydrogel. The glycerol/water solvent slowed the diffusion of TP into the NAGA/GelMA/Laponite (NGL)hydrogel, thereby avoiding excessive crosslinking, and forming a uniform network. The hydrogel exhibited excellent water retention (84% within 28 days). Additionally, due to the hygroscopicity of glycerol, the hydrogel's mechanical strength (0.73-1.14 MPa) and tensile strain (207%-353%) increased further after 14 days in an open environment. Additionally, the hydrogel exhibited superior anti-ultraviolet and antioxidant properties, which effectively alleviated the wound site's oxidative stress and accelerated wound healing. Moreover, antibacterial activity was observed against both E. coli and S. aureus in the hydrogel wound dressing. Thus, by promoting wound closure, angiogenesis and collagen deposition, the double-network NGLG20/TG hydrogel dressing can successfully accelerate wound healing. The multifunctional double-network hydrogel, therefore, shows immense potential as an ideal candidate for wound dressings because it is long-lasting and prevents secondary damage caused by frequent dressing changes.