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.

The Influence of the First-Stage DO Treatment of Palate Defect on Growth of Maxilla.

To study the influence of distraction osteogenesis (DO) on the maxillary growth as first-stage treatment of palatal defect. The uniform palate defect experimental animal models (21 miniature pigs) were established surgically. Then animals were randomly divided into negative control group (A, n = 6), conventional surgery group (B, n = 6), and distraction osteogenesis group (C, n = 9) respectively. The group A underwent none treatment as control group, the group B were undergoing a conventional defect repair surgery, and the group C were undergoing a distraction osteogenesis treatment. Cone beam computed tomography examination was performed monthly to analyze the growth of maxilla for 6 months. One pig of group C was randomly sacrificed at 2, 4, and 8 weeks after the completion of DO and the tissue of distraction gap was stained with hematoxylin-eosin and Masson staining. At the end of 6th months, all pigs were sacrificed and tissues of the surgical area were stained as previous described. The palate defect was repaired by the distraction osteogenesis with the successful bone formation on the distraction gap. Group A and group C kept a similar growth rate, but that of group B was relatively slow. Distraction osteogenesis is efficient and successful for closing the defect of palate and there is no significant disturbance on the subsequent growth of the maxilla.

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.

3D printed TPMS structural PLA/GO scaffold: Process parameter optimization, porous structure, mechanical and biological properties.

Bone scaffolds should have good biocompatibility and mechanical and biological properties, which are primarily by the material design, porous structure, and preparation process. In this study, we proposed polylactic acid (PLA) as the base material, graphene oxide (GO) as an enhancing filler, triply periodic minimal surface (TPMS) as a porous structure, and fused deposition modeling (FDM) 3D printing as a preparation technology to develop a TPMS structural PLA/GO scaffold and evaluate their porous structures, mechanical properties, and biological properties towards bone tissue engineering. Firstly, the influence of the FDM 3D printing process parameters on the forming quality and mechanical properties of PLA was studied by orthogonal experimental design, based on which the process parameters were optimized. Then, GO was composited with PLA, and PLA/GO nanocomposites were prepared by FDM. The mechanical tests showed that GO can effectively improve the tensile and compression strength of PLA; only by adding 0.1% GO the tensile and compression modulus was increased by 35.6% and 35.8%, respectively. Then, TPMS structural (Schwarz-P, Gyroid) scaffold models were designed and TPMS structural PLA/0.1%GO nanocomposite scaffolds were prepared by FDM. The compression test showed that the TPMS structural scaffolds had higher compression strength than the Grid structure; This was owing to the fact that the continuous curved structure of TMPS alleviated stress concentration and had a more uniform stress bearing. Moreover, cell culture indicated bone marrow stromal cells (BMSCs) showed better adhesion, proliferation, and osteogenic differentiation behaviors on the TPMS structural scaffolds as the continuous surface structure of TPMS had better connectivity and larger specific surface area. These results suggest that the TPMS structural PLA/GO scaffold has potential application in bone repair. This article suggests the feasibility of co-designing the material, structure, and technology for achieving the good comprehensive performance of polymer bone scaffolds.

Design, development and clinical validation of computer-aided surgical simulation system for streamlined orthognathic surgical planning.

PURPOSE: There are many proven problems associated with traditional surgical planning methods for orthognathic surgery. To address these problems, we developed a computer-aided surgical simulation (CASS) system, the AnatomicAligner, to plan orthognathic surgery following our streamlined clinical protocol. METHODS: The system includes six modules: image segmentation and three-dimensional (3D) reconstruction, registration and reorientation of models to neutral head posture, 3D cephalometric analysis, virtual osteotomy, surgical simulation, and surgical splint generation. The accuracy of the system was validated in a stepwise fashion: first to evaluate the accuracy of AnatomicAligner using 30 sets of patient data, then to evaluate the fitting of splints generated by AnatomicAligner using 10 sets of patient data. The industrial gold standard system, Mimics, was used as the reference. RESULT: When comparing the results of segmentation, virtual osteotomy and transformation achieved with AnatomicAligner to the ones achieved with Mimics, the absolute deviation between the two systems was clinically insignificant. The average surface deviation between the two models after 3D model reconstruction in AnatomicAligner and Mimics was 0.3 mm with a standard deviation (SD) of 0.03 mm. All the average surface deviations between the two models after virtual osteotomy and transformations were smaller than 0.01 mm with a SD of 0.01 mm. In addition, the fitting of splints generated by AnatomicAligner was at least as good as the ones generated by Mimics. CONCLUSION: We successfully developed a CASS system, the AnatomicAligner, for planning orthognathic surgery following the streamlined planning protocol. The system has been proven accurate. AnatomicAligner will soon be available freely to the boarder clinical and research communities.

A clinically validated prediction method for facial soft-tissue changes following double-jaw surgery.

PURPOSE: It is clinically important to accurately predict facial soft-tissue changes prior to orthognathic surgery. However, the current simulation methods are problematic, especially in anatomic regions of clinical significance, e.g., the nose, lips, and chin. We developed a new 3-stage finite element method (FEM) approach that incorporates realistic tissue sliding to improve such prediction. METHODS: In Stage One, soft-tissue change was simulated, using FEM with patient-specific mesh models generated from our previously developed eFace template. Postoperative bone movement was applied on the patient mesh model with standard FEM boundary conditions. In Stage Two, the simulation was improved by implementing sliding effects between gum tissue and teeth using a nodal force constraint scheme. In Stage Three, the result of the tissue sliding effect was further enhanced by reassigning the soft-tissue-bone mapping and boundary conditions using nodal spatial constraint. Finally, our methods have been quantitatively and qualitatively validated using 40 retrospectively evaluated patient cases by comparing it to the traditional FEM method and the FEM with sliding effect, using a nodal force constraint method. RESULTS: The results showed that our method was better than the other two methods. Using our method, the quantitative distance errors between predicted and actual patient surfaces for the entire face and any subregions thereof were below 1.5 mm. The overall soft-tissue change prediction was accurate to within 1.1 ± 0.3 mm, with the accuracy around the upper and lower lip regions of 1.2 ± 0.7 mm and 1.5 ± 0.7 mm, respectively. The results of qualitative evaluation completed by clinical experts showed an improvement of 46% in acceptance rate compared to the traditional FEM simulation. More than 80% of the result of our approach was considered acceptable in comparison with 55% and 50% following the other two methods. CONCLUSION: The FEM simulation method with improved sliding effect showed significant accuracy improvement in the whole face and the clinically significant regions (i.e., nose and lips) in comparison with the other published FEM methods, with or without sliding effect using a nodal force constraint. The qualitative validation also proved the clinical feasibility of the developed approach.

[The effect of dog bilateral distraction osteogensis in temporomandibular joint].

OBJECTIVE: To investigate the effect of bilateral mandibular distraction osteogenesis in the condyles. METHODS: 16 adult hybrid dogs were randomly divided into normal control group and experiment group. Experimental dogs underwent bilateral mandibular osteodistraction at a rate of 1 min/day. 4 dogs were killed respectively in distraction period, 2 and 8 weeks after completion of 10 days distraction. The bilateral condyles specimens were harvested and examined with histological and immunohistochemical methods. RESULTS: Compared with normal control group, various degrees of irregularities and erosion were found in fibrocartilage of condyle in experiment group, including damage in fibrous layer, hyperplasia layer and proliferative layer and osteogenic activity in cartilage layer. A significant increase of TGF-beta1 expression was also found in experiment groups. TGF-beta1 positive staining was noted in hypertrophic cell, matrix and chondroblast, osteoblast and matrix in osteogenic activity areas. These changes were the most obvious in 2 weeks after completion of distraction. CONCLUSION: Gradual bilateral mandibular distraction at a rate of 1 mm/day brought degenerative changes of condyle, but the changes are reversible.