Fabrication of gelatin-based and Zn2+-incorporated composite hydrogel for accelerated infected wound healing.

Gelatin-based hydrogels have a broad range of biomedical fields due to their biocompatibility, convenience for chemical modifications, and degradability. However, gelatin-based hydrogels present poor antibacterial ability that hinders their applications in treating infected wound healing. Herein, a series of multifunctional hydrogels (Gel@Zn) were fabricated through free-radical polymerization interaction based on gelatin methacrylate (GelMA) and dopamine methacrylate (DMA), and then immersed them into zinc nitrate solutions based on the metal coordination and ionic bonding interaction. These designed hydrogels wound dressings show strong antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by increasing intracellular reactive oxygen species (ROS) level and changing bacterial membrane permeability. Meanwhile, the hydrogels exhibit good cytocompatibility, enhance the adhesion, proliferation, and migration of NIH-3T3 cells. Furthermore, Gel@Zn-0.08 (0.08 â€‹M Zn2+ immersed with Gel sample) presents a good balance between antibacterial effect, cell viability, and hemolytic property. Compared with 3 â€‹M commercial dressings, Gel@Zn-0.04, and Gel@Zn-0.16, the Gel@Zn-0.08 could significantly improve the healing process of S. aureus-infected full-thickness wounds via restrained the inflammatory responses, enhanced epidermis and granulation tissue information, and stimulated angiogenesis. Our study indicates that the Zn-incorporated hydrogels are promising bioactive materials as wound dressings for infected full-thickness wound healing and skin regeneration.

Effects of a novel self-assembling peptide scaffold on bone regeneration and controlled release of two growth factors.

RADA16 is a self-assembling peptide material with good bioactivity. To improve the bioactivity of a material, some specific functional motifs can be added to its peptide sequence. Here, we report a self-assembling peptide nanogel, RADA16-RGD, that has better bioactivity than RADA16 and can simultaneously carry and control the release of two growth factors, VEGF and BMP-2, which have synergistic effects on bone formation. The peptide materials were characterized by transmission electron microscopy and scanning electron microscopy. The mechanical properties of the peptides were evaluated by the rheology test. The biocompatibility of the materials was evaluated via the use of the CCK-8 test, live/dead staining and confocal laser scanning microscopy. Osteogenesis capability in vitro was evaluated by means of ALP staining, extracellular matrix mineralization and detection of osteogenic markers. The controlled release of growth factors was examined by ELISA. The results showed that RADA16-RGD exhibited a better ability than RADA16 to promote cell proliferation, adhesion and bone formation. In addition, RADA16-RGD had good biocompatibility and exhibited effective controlled release of VEGF and BMP-2. More importantly, compared with RADA16-RGD loaded with single growth factor or without growth factors, RADA16-RGD loaded with two growth factors exhibited a stronger ability to promote cell proliferation and osteogenesis. This study provides a promising strategy for the application of self-assembling peptides to promote osteogenesis and controlled release of proteins.

Gallium (Ga)-strontium (Sr) layered double hydroxide composite coating on titanium substrates for enhanced osteogenic and antibacterial abilities.

Bacterial infection and poor osteogenic capacity can result in the loosing or failure of titanium (Ti)-based implants in the clinic. Therefore, it is urgent to design an effective approach to enhance the osteogenic property and restrict bacterial activity. In this study, a layered double hydroxide (LDH) composed of Ga and Sr ions on Ti substrates by a hydrothermal method, then calcined in 250°C and denoted as LDH250. The scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) were confirmed that the LDH films were successfully formed on the Ti substrates. Importantly, the obtained LDH films can induce an alkaline microenvironment around the Ti surface and regulate the behaviors of osteogenic cells and bacteria. In vitro cellular experiments, the LDH250 can enhance the differentiation of both MC3T3-E1 cells and osteoblasts, stimulate alkaline phosphatase activity (ALP), collagen secretion, and mineralization levels. Meanwhile, antimicrobial assay against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) demonstrated that the LDH250 samples had strong antibacterial abilities, which attributed to the release profile of Ga3+ could act as a "Trojan horse" to destroy the bacterial iron metabolism, inducing of local alkaline environment, and producing reactive oxygen species. Hence, this study provides an effective method for reducing antibacterial infection and enhancing the bone integrative capacity of Ti-based implants for orthopedic applications.

FGF19 protects against obesity-induced bone loss by promoting osteogenic differentiation.

Human fibroblast growth factor 19 (FGF19) has become a potential therapeutic target for metabolic-related diseases. However, the effects of FGF19 on obesity-induced bone loss have not been completely elucidated. The aim of this study was to investigate the protective effects of FGF19 in high-fat diet (HFD)-fed obese mice and palmitic acid (PA)-treated osteoblasts and to further explore its underlying mechanisms. In vivo, we found that FGF19 alleviated the decreased bone mineral density (BMD) induced by HFD. Micro-CT analysis of femur samples and histological analysis indicated that FGF19 alleviated HFD-induced loss of bone trabeculae and damage to the bone trabecular structure. In vitro, the results suggested that FGF19 ameliorated the PA-induced decline in osteoblast proliferation, increased cell death and impaired cell morphology. Additionally, FGF19 protected against the decline in activation of alkaline phosphatase (ALP) and protein expression of Collagen-1, Runx-2, and osteopontin (OPN) induced by PA. Furthermore, FGF19 might enhance osteogenic differentiation via the Wnt/ß-catenin pathway and inhibit osteoclastogenesis by regulating the osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) axis, thus attenuating the negative effect of PA in osteoblasts. In conclusion, our results suggested that FGF19 might promote osteogenic differentiation partially through activation of the Wnt/ß-catenin pathway and alleviate obesity-induced bone loss.

FGF19 protects skeletal muscle against obesity-induced muscle atrophy, metabolic derangement and abnormal irisin levels via the AMPK/SIRT-1/PGC-α pathway.

Obesity is associated with biological dysfunction in skeletal muscle. As a condition of obesity accompanied by muscle mass loss and physical dysfunction, sarcopenic obesity (SO) has become a novel public health problem. Human fibroblast growth factor 19 (FGF19) plays a therapeutic role in metabolic diseases. However, the protective effects of FGF19 on skeletal muscle in obesity and SO are still not completely understood. Our results showed that FGF19 administration improved muscle loss and grip strength in young and aged mice fed a high-fat diet (HFD). Increases in muscle atrophy markers (FOXO-3, Atrogin-1, MuRF-1) were abrogated by FGF19 in palmitic acid (PA)-treated C2C12 myotubes and in the skeletal muscle of HFD-fed mice. FGF19 not only reduced HFD-induced body weight gain, excessive lipid accumulation and hyperlipidaemia but also promoted energy expenditure (PGC-1α, UCP-1, PPAR-γ) in brown adipose tissue (BAT). FGF19 treatment restored PA- and HFD-induced hyperglycaemia, impaired glucose tolerance and insulin resistance (IRS-1, GLUT-4) and mitigated the PA- and HFD-induced decrease in FNDC-5/irisin expression. However, these beneficial effects of FGF19 on skeletal muscle were abolished by inhibiting AMPK, SIRT-1 and PGC-1α expression. Taken together, this study suggests that FGF19 protects skeletal muscle against obesity-induced muscle atrophy, metabolic derangement and abnormal irisin secretion partially through the AMPK/SIRT-1/PGC-α signalling pathway, which might be a potential therapeutic target for obesity and SO.

A novel biocomposite scaffold with antibacterial potential and the ability to promote bone repair.

Clinical treatment of bone defects caused by trauma, tumor resection and other bone diseases, especially bone defects that can lead to infection, remains a major challenge. Currently, autologous bone implantation is the gold standard for treatment of bone defects, but it is limited by secondary trauma and insufficient autologous material. Moreover, postoperative infection is an important factor affecting bone healing.AcN-RADARADARADARADA-CONH2 (RADA) is a new type of self-assembling peptide(SAP) composed of Arg,Ala,Asp and other amino acids was designed and prepared. The "RADA" self-assembling peptide hydrogels has excellent biological activity and it's completely biodegradable and non-toxic.It is also have been confirmed to promote cell proliferation, wound healing, tissue repair, and drug delivery. To promote bone regeneration and simultaneously prevent bacterial infection, we designed biocomposite scaffolds comprising RADA and calcium phosphate cement (CPC), termed RADA-CPC. The morphological features of the scaffold were characterized by scanning electron microscopy (SEM). In vitro studies demonstrated that RADA-CPC enhances osteoblast proliferation, differentiation and mineralization. In addition, the scaffold was used as a drug delivery system to treat postoperative infections by sustained release of ciprofloxacin (CIP). The RADA-CPC scaffold may have potential application prospects in orthopedics field because of its role in promoting bone repair and as a sustained-release drug carrier to prevent infections.