Injectable thermo-responsive Poloxamer hydrogel/methacrylate gelatin microgels stimulates bone regeneration through biomimetic programmed release of SDF-1a and IGF-1.

Injectable hydrogels, offering adaptable drug delivery of growth factors (GFs), hold promise for treating bone defects. To optimize osteogenic efficacy, the release of GFs should mirror the natural bone healing. We developed an injectable thermo-responsive hydrogel/microgels platform for dual GF delivery for bone regeneration. Stromal cell-derived factor-1 alpha (SDF-1a) and the Methacrylate Gelatin (GelMA) microgels which encapsulated insulin-like growth factor-1 (IGF-1) loaded liposomes (Ls) were introduced into Poloxamer 407 (P407) hydrogel matrix. This system achieved the biomimetic release profile of SDF-1a and IGF-1, which covered the early stage from day 1 to 7 and the continuous stage from day 5 to 21, respectively. In vitro study confirmed the enhanced migration, osteogenic biomarker expression, and matrix mineralization of the bone marrow mesenchymal stem cells (BMSCs) co-cultivated with the dual GFs delivering hydrogel/microgels. Transcriptome sequencing revealed that the potential mechanism was associated with mitogen-activated protein kinase (MAPK) signaling activation and its downstream ribosomal protein S6 kinase 2 (RSK2) upregulation. In a critical-sized calvarial defect model in Sprague-Dawley (SD) rats, the injectable hydrogel/microgels system promoted significant bone regeneration. Collectively, our study suggested the current hydrogel/microgels system with the biomimetic release of SDF-1a and IGF-1 efficiently promoted bone regeneration, informing the future development of GF delivery systems intended for bone regeneration therapies.

NIR-activated electrospun nanodetonator dressing enhances infected diabetic wound healing with combined photothermal and nitric oxide-based gas therapy.

Diabetic wounds pose a challenge to healing due to increased bacterial susceptibility and poor vascularization. Effective healing requires simultaneous bacterial and biofilm elimination and angiogenesis stimulation. In this study, we incorporated polyaniline (PANI) and S-Nitrosoglutathione (GSNO) into a polyvinyl alcohol, chitosan, and hydroxypropyltrimethyl ammonium chloride chitosan (PVA/CS/HTCC) matrix, creating a versatile wound dressing membrane through electrospinning. The dressing combines the advantages of photothermal antibacterial therapy and nitric oxide gas therapy, exhibiting enduring and effective bactericidal activity and biofilm disruption against methicillin-sensitive Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Escherichia coli. Furthermore, the membrane's PTT effect and NO release exhibit significant synergistic activation, enabling a nanodetonator-like burst release of NO through NIR irradiation to disintegrate biofilms. Importantly, the nanofiber sustained a uniform release of nitric oxide, thereby catalyzing angiogenesis and advancing cellular migration. Ultimately, the employment of this membrane dressing culminated in the efficacious amelioration of diabetic-infected wounds in Sprague-Dawley rats, achieving wound closure within a concise duration of 14 days. Upon applying NIR irradiation to the PVA-CS-HTCC-PANI-GSNO nanofiber membrane, it swiftly eradicates bacteria and biofilm within 5 min, enhancing its inherent antibacterial and anti-biofilm properties through the powerful synergistic action of PTT and NO therapy. It also promotes angiogenesis, exhibits excellent biocompatibility, and is easy to use, highlighting its potential in treating diabetic wounds.

Electrospun polyvinyl alcohol-chitosan dressing stimulates infected diabetic wound healing with combined reactive oxygen species scavenging and antibacterial abilities.

Diabetic wounds (DW) are constantly challenged by excessive reactive oxygen species (ROS) accumulation and susceptibility to bacterial contamination. Therefore, the elimination of ROS in the immediate vicinity and the eradication of local bacteria are critical to stimulating the efficient healing of diabetic wounds. In the current study, we encapsulated mupirocin (MP) and cerium oxide nanoparticles (CeNPs) into a polyvinyl alcohol/chitosan (PVA/CS) polymer, and then a PVA/chitosan nanofiber membrane wound dressing was fabricated using electrostatic spinning, which is a simple and efficient method for fabricating membrane materials. The PVA/chitosan nanofiber dressing provided a controlled release of MP, which produced rapid and long-lasting bactericidal activity against both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains. Simultaneously, the CeNPs embedded in the membrane exhibited the desired ROS scavenging capacity to maintain the local ROS at a normal physiological level. Moreover, the biocompatibility of the multifunctional dressing was evaluated both in vitro and in vivo. Taken together, PVA-CS-CeNPs-MP integrated the desirable features of a wound dressing, including rapid and broad-spectrum antimicrobial and ROS scavenging activities, easy application, and good biocompatibility. The results validated the effectiveness of our PVA/chitosan nanofiber dressing, highlighting its promising translational potential in the treatment of diabetic wounds.