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.

The long-term curative effect analysis of trans-articular plate combined with Kirschner wires in the treatment of fracture-dislocation of the fifth carpometacarpal joint.

Purpose: To evaluate the long-term curative effect analysis of trans-articular plate combined with Kirschner wires in the treatment of fracture-dislocation of the fifth carpometacarpal joint. Methods: From July 2016 to September 2021, 21 patients with fracture-dislocation of the fifth carpometacarpal joint were treated with trans-articular plate combined with Kirschner wires internal fixation. Each patient's gender, age, dominant hand, injured hand, trauma mechanism, the time between injury and surgery, the range of motion of the bilateral wrist in flexion, extension, radial deviation and ulnar deviation, grip strength of each side, the time of return to work, and follow-up time were recorded. The QDASH score and Cooney wrist function score were used to evaluate the postoperative function. The VAS system was used to evaluate postoperative pain. Results: The follow-up time was 37.0 ± 19.0 months and the time between injury and surgery was 1.3 ± 0.5 days. In the injured side and the contralateral side, the range of motion of the wrist flexion were 58.3 ± 4.0° and 60.5 ± 3.1°, the range of motion of the wrist radial deviation were 25.7 ± 3.3° and 26.9 ± 2.9°, the range of motion of the wrist ulnar deviation were 28.1 ± 3.7° and 29.5 ± 3.1° respectively with no significant difference. The range of motion of the wrist extension (54.0 ± 3.4°) in the injured side was smaller than that in the contralateral side (56.7 ± 3.7°) with significant difference. The grip strength of the injured side and the contralateral side were 96.1 ± 9.5 LB and 100.7 ± 9.7LB respectively with no significant difference. The QDASH score was 3.8 ± 1.8, Cooney wrist function score was 94.5 ± 4.2, VAS score was 1.0 ± 0.8 and the time of return to work was 5.1 ± 0.9 weeks. In the 21 cases, no postoperative complications such as incision infection, failure of internal fixation, fracture nonunion or fracture malunion occurred. Conclusion: The method of trans-articular plate combined with Kirschner wires is one of the alternative treatments for the fracture-dislocation of the fifth carpometacarpal joint. The long-term follow-up results were satisfactory.

The curative effect analysis of a modified Kirschner wires and locking plate internal fixation method for the fifth metacarpal neck fracture.

PURPOSE: To evaluate the efficacy of a modified internal fixation method for the treatment of fifth metacarpal neck fracture. METHODS: From March 2018 to December 2019, 12 patients with the fifth metacarpal neck fractures of the hands were treated with the Kirschner wires and locking plate internal fixation method. Each patient's gender, age, dominant hand, injured hand, trauma mechanism, preoperative and postoperative deformity (angulation and the length of the fifth metacarpal), the range of motion of the metacarpophalangeal joint and grip strength of each side, the time of return to work, and follow-up time were recorded and calculated. RESULTS: The mean follow-up time was 16.8 months, and the angulations of preoperative and postoperative deformity were 40.0 ± 3.7°and 17.6 ± 1.7°, respectively. The length of the fifth metacarpals of preoperative and postoperative deformity were 51.5 ± 2.1 mm and 60.0 ± 1.8 mm, respectively. At the last follow-up, the range of motion of the fifth metacarpophalangeal joint of the injured side and the contralateral side were 84.3 ± 3.6°and 86.5 ± 2.0°, and the grip strength of the injured side and the contralateral side were 74.8 ± 6.1 LB and 78.6 ± 8.3 LB, respectively, without statistically significant differences. QDASH score was 2.0 ± 1.0, and the time of return to work was 6.0 ± 0.7 weeks. CONCLUSION: The modified internal fixation method is one of the alternative treatments for the fifth metacarpal neck fracture with good curative effects.

Flow-through arterialized venous free thenar flaps for palmar soft tissue defects in fingers.

OBJECTIVE: To evaluate the efficacy of venous free thenar flaps for reconstructing palmar soft tissue defects in fingers. METHODS: From December 2018 to October 2019, 11 patients with palmar soft tissue defects in fingers were treated using venous free thenar flaps. At the final follow-up, the range of thumb radial and palmar abduction on the injured side and opposite side was calculated. The total active movement (TAM) of the injured and opposite fingers and flap sensibility recovery were also recorded. RESULTS: The mean follow-up time was 13.4 months, all flaps survived, and all wounds at the donor sites healed with no skin necrosis. At the last follow-up, the average range of thumb radial abduction and thumb palmar abduction on the injured side was 96.6% and 95.9% of the value on the opposite side, respectively. The average TAM of the injured fingers was 98.2% of the value of the opposite fingers. Sensation in the flaps was restored to grade S2 to S3. CONCLUSION: Venous free thenar flaps can be alternatives for reconstructing palmar soft tissue defects in fingers.

Comparison of the modified direct closure method and skin grafting for wounds at the anterolateral thigh flap donor site.

OBJECTIVE: This study was performed to compare the modified direct closure method and traditional skin grafting for wounds at the anterolateral thigh (ALT) flap donor site. METHODS: Among 29 consecutive patients with wounds at the ALT flap donor site, 14 underwent the modified direct closure method (MDC group) and 15 underwent traditional skin grafting (SG group). The operative time, follow-up time, complications, Vancouver Scar Scale (VSS) score, and Scar Cosmesis Assessment and Rating (SCAR) score of the two groups were statistically analyzed. RESULTS: The mean follow-up times in the MDC and SG group were 16.1 and 16.7 months, respectively. Two patients showed partial skin necrosis after skin grafting, but the remaining patients' wounds healed uneventfully. The operative time in the MDC group was an average of about 64 minutes shorter than that in the SG group. The average VSS and SCAR scores in the MDC group were 2.1 and 3.0 points lower, respectively, than those in the SG group. CONCLUSIONS: Compared with traditional skin grafting, the modified direct closure method is more efficient for repair of wounds at the ALT flap donor site because of its shorter operative time, better postoperative appearance of the donor site, and higher patient satisfaction.

Immediate weightbearing after intramedullary fixation of extra-articular distal tibial fractures reduces the nonunion rate compared with traditional weight-bearing protocol: A cohort study.

OBJECTIVES: To investigate whether immediate weightbearing after intramedullary fixation of extra-articular distal tibial fractures could avoid secondary replacement. METHODS: We prospectively included 167 patients receiving intramedullary nailing in treatment of distal tibial fractures. All these patients were encouraged to bear weight as tolerated postoperatively. One hundred and fifty-five patients who did not bear weight immediately after surgery were retrospectively included as historical control. RESULTS: The mean immediate lateral and anterior DTA were 88.9 ± 3.9 and 85.2 ± 3.5° for historical control and 88.7 ± 3.6 and 84.9 ± 3.8° for immediate weight bearing group (lateral DTA: P = 0.715; anterior DTA: P = 0.734). The mean final lateral and anterior DTA were 88.1 ± 3.3 and 84.1 ± 4.3° for historical control and 87.9 ± 5.0 and 84.5 ± 5.1° for the immediate weightbearing group (lateral DTA: P = 0.857; anterior DTA: P = 0.788). Strikingly, the immediate weightbearing resulted in accelerated healing (3.5 ± 1.2 versus 4.9 ± 1.3 months, P = 0.023) and decreased nonunion rate (2.4% versus 7.1%, P = 0.027). The rates of infection and soft-tissue necrosis were similar between the two groups. CONCLUSIONS: Immediate weightbearing after IMN fixation of extra-articular distal tibial fractures led to a similar change in alignment compared with our historical control without immediate weightbearing. Immediate weightbearing appears to be safe for most patients and might be able to accelerate fracture healing and decrease nonunion rate.

Dimethyloxallyl Glycine-Incorporated Borosilicate Bioactive Glass Scaffolds for Improving Angiogenesis and Osteogenesis in Critical-Sized Calvarial Defects.

BACKGROUND: In the field of bone tissue engineering, there has been an increasing interest in biomedical materials with both high angiogenic ability and osteogenic ability. Among various osteogenesis materials, bioactive borosilicate and borate glass scaffolds possess suitable degradation rate and mechanical strength, thus drawing many scholars' interests and attention. OBJECTIVE: In this study, we fabricated bioactive glass scaffolds composed of borosilicate 2B6Sr using the Template-Method and incorporated Dimethyloxalylglycine (DMOG), a small-molecule angiogenic drug possessing good angiogenic ability, to improve bone regeneration. METHODS: The in-vitro studies showed that porous borosilicate bioactive glass scaffolds released slowly, a steady amount of DMOG and stimulated the proliferation and osteogenic differentiation of human bone marrow stromal cells hBMSCs. RESULTS: In-vivo studies showed that the borosilicate bioactive glass scaffolds could significantly promote new bone formation and neovascularization in rats' calvarial bone defects. CONCLUSION: These results indicated that DMOG-incorporated bioactive glass scaffold is a successful compound with excellent angiogenesis-osteogenesis ability, which has favorable clinical prospects.

Downregulation of coding transmembrane protein 35 gene inhibits cell proliferation, migration and cell cycle arrest in osteosarcoma cells.

Osteosarcoma (OSA) is the most common primary tumor of the bone. Resistance to chemotherapy and the fast rapid development of metastatic lesions are major issues responsible for treatment failure and poor survival rates in OSA patients. Tetraspanins comprise a family of transmembrane receptor glycoproteins that affect tumor cell migration through tetraspanin-integrin interaction. The present study focused on a four-pass transmembrane protein gene, transmembrane protein 35 (TMEM35) gene, and examined its role in the growth, migration and cell cycle progression of OSA cells. In addition, the study discussed whether the TMEM35 gene, which encodes the TMEM35 protein, may be a potential therapeutic target for OSA. In the current study, reverse transcription-quantitative polymerase chain reaction was performed to examine TMEM35 expression in OSA and matched healthy tissues. Small interfering RNAs (siRNAs) were transfected into SaOS2 and U2OS cells to knockdown the TMEM35 expression. Soft-agar colony formation assay was performed to evaluate cell growth, and cell cycle progression was analyzed by flow cytometry. Wound-healing and Boyden chamber assays were also performed to investigate cell invasion and migration by the SaOS2 and U2OS cells. TMEM35 protein was analyzed in a functional protein interaction networks database (STRING database) to predict the functional interaction partner proteins of TMEM35. The results indicated that TMEM35 was abnormally expressed in OSA tissues. Of the 37 examined patients, TMEM35 expression was significantly increased in the OSA tissues of 24 patients (64.86%; P<0.05), when compared with the expression in normal tissues. Furthermore, TMEM35 knockdown following transfection with siRNAs inhibited the colony formation ability of SaOS2 and U2OS cells in soft agar. Flow cytometric analysis also revealed that TMEM35 knockdown by RNA interference may result in G1 phase arrest and a decreased cell population at the S phase. TMEM35 knockdown inhibited cell migration in SaOS2 and U2OS cells in wound-healing assays. In conclusion, TMEM35, a member of the tetraspanin family, serves an important role in the growth of OSA cells.

Increased Effects of Extracorporeal Shock Waves Combined with Gentamicin against Staphylococcus aureus Biofilms In Vitro and In Vivo.

An implant-associated bacterial infection is one of the most common and costly complications of orthopedic surgery. Once biofilms develop, it is extremely difficult to cure infections with antimicrobial agents. High-energy extracorporeal shock wave (ESW) treatment has been used for orthopedic-related diseases and has been found to be an effective bactericidal agent that is tolerable both in vitro and in vivo. The broad-spectrum antibiotic gentamicin exhibits bactericidal activity against Staphylococcus aureus, and bacterial resistance to gentamicin is lower. We tested the effectiveness of gentamicin in combination with ESW treatment against S. aureus biofilms in vivo and in vitro. The spread plate method, crystal violet staining, confocal laser scanning microscopy, scanning electron microscopy and microbiologic evaluation were used to compare the effects of combined treatment with those of either treatment alone. The results revealed statistically significant differences between the group treated with ESWs combined with gentamicin and all other groups. Our findings indicate that use of the combination of ESWs with gentamicin is more effective against S. aureus biofilms in vitro and in vivo.

Three-dimensional poly (ε-caprolactone)/hydroxyapatite/collagen scaffolds incorporating bone marrow mesenchymal stem cells for the repair of bone defects.

We previously demonstrated that three-dimensional (3D) hydroxyapatite (HAP)-collagen (COL)-coated poly(ε-caprolactone) (PCL) scaffolds (HAP-COL-PCL) possess appropriate nano-structures, surface roughness, and nutrients, providing a favorable environment for osteogenesis. However, the effect of using 3D HAP-COL-PCL scaffolds incorporating BMSCs for the repair of bone defects in rats has been not evaluated. 3D PCL scaffolds coated with HAP, collagen or HAP/COL and incorporating BMSCs were implanted into calvarial defects. At 12 weeks after surgery, the rats were sacrificed and crania were harvested to assess the bone defect repair using microcomputed tomography (micro-CT), histology, immunohistochemistry and sequential fluorescent labeling analysis. 3D micro-CT reconstructed images and quantitative analysis showed that HAP-COL-PCL groups possessed better bone-forming capacity than HAP-PCL groups or COL-PCL groups. Fluorescent labeling analysis revealed the percentage of tetracycline labeling, alizarin red labeling, and calcein labeling in HAP-COL-PCL groups were all greater than in the other two groups (P < 0.05), and the result was confirmed by immunohistochemical staining and histological analysis of bone regeneration. This study demonstrates that 3D HAP-COL-PCL scaffolds incorporating BMSCs markedly enhance bone regeneration of bone defects in rats.

Downregulation of connective tissue growth factor reduces migration and invasiveness of osteosarcoma cells.

As one of the most serious types of primary bone tumor, osteosarcoma (OSA) features metastatic lesions, and resistance to chemotherapy is common. The underlying mechanisms of these characteristics may account for the failure of treatments and the poor prognosis of patients with OSA. It has been reported that inhibition of Cyr61 suppresses OSA cell proliferation as it represents a target of statins. In addition to cystein­rich protein 61 (Cyr61) and nephroblastoma overexpression, connective tissue growth factor (CTGF) is a member of the CCN family and may therefore exhibit effects on human OSA cells similar to those of Cyr61. In the current study, acridine orange/ethidium bromide staining were used to determine the rate of apoptosis. The present study demonstrated that small interfering RNA­mediated silencing of CTGF promoted cell death and suppressed OSA cell migration and invasion, as indicated by wound healing and Transwell assays, while lentivirus­mediated overexpression of CTGF reversed these effects. Furthermore, a colorimetric caspase assay demonstrated that CTGF knockdown enhanced the efficacy of chemotherapeutic drugs. The results of the present study provided a novel molecular target which may be utilized for the treatment of metastatic OSA.

Highly Regio-, Diastereo-, and Enantioselective Mannich Reaction of Allylic Ketones and Cyclic Ketimines: Access to Chiral Benzosultam.

An organocatalytic asymmetric Mannich reaction of allylic ketones with cyclic N-sulfonyl α-iminoester has been developed. By using a saccharide-derived chiral tertiary amino-thiourea catalyst, a range of allylic ketones and N-sulfonyl ketimines reacted smoothly to afford tetrasubstituted α-amino esters in high yields with good to excellent regio-, diastero-, and enantioselectivities.

Three-dimensional printing of strontium-containing mesoporous bioactive glass scaffolds for bone regeneration.

In this study, we fabricated strontium-containing mesoporous bioactive glass (Sr-MBG) scaffolds with controlled architecture and enhanced mechanical strength using a three-dimensional (3-D) printing technique. The study showed that Sr-MBG scaffolds had uniform interconnected macropores and high porosity, and their compressive strength was ∼170 times that of polyurethane foam templated MBG scaffolds. The physicochemical and biological properties of Sr-MBG scaffolds were evaluated by ion dissolution, apatite-forming ability and proliferation, alkaline phosphatase activity, osteogenic expression and extracelluar matrix mineralization of osteoblast-like cells MC3T3-E1. The results showed that Sr-MBG scaffolds exhibited a slower ion dissolution rate and more significant potential to stabilize the pH environment with increasing Sr substitution. Importantly, Sr-MBG scaffolds possessed good apatite-forming ability, and stimulated osteoblast cells' proliferation and differentiation. Using dexamethasone as a model drug, Sr-MBG scaffolds also showed a sustained drug delivery property for use in local drug delivery therapy, due to their mesoporous structure. Therefore, the 3-D printed Sr-MBG scaffolds combined the advantages of Sr-MBG such as good bone-forming bioactivity, controlled ion release and drug delivery and enhanced mechanical strength, and had potential application in bone regeneration.