Acidity-Activatable Nanoparticles with Glucose Oxidase-Enhanced Photoacoustic Imaging and Photothermal Effect, and Macrophage-Related Immunomodulation for Synergistic Treatment of Biofilm Infection.

The pH-responsive theragnostics exhibit great potential for precision diagnosis and treatment of diseases. Herein, acidity-activatable nanoparticles of GB@P based on glucose oxidase (GO) and polyaniline are developed for treatment of biofilm infection. Catalyzed by GO, GB@P triggers the conversion of glucose into gluconic acid and hydrogen peroxide (H2 O2 ), enabling an acidic microenvironment-activated simultaneously enhanced photothermal (PT) effect/amplified photoacoustic imaging (PAI). The synergistic effects of the enhanced PT efficacy of GB@P and H2 O2 accelerate biofilm eradication because the penetration of H2 O2 into biofilm improves the bacterial sensitivity to heat, and the enhanced PT effect destroys the expressions of extracellular DNA and genomic DNA, resulting in biofilm destruction and bacterial death. Importantly, GB@P facilitates the polarization of proinflammatory M1 macrophages that initiates macrophage-related immunity, which enhances the phagocytosis of macrophages and secretion of proinflammatory cytokines, leading to a sustained bactericidal effect and biofilm eradication by the innate immunomodulatory effect. Accordingly, the nanoplatform of GB@P exhibits the synergistic effects on the biofilm eradication and bacterial residuals clearance through a combination of the enhanced PT effect with immunomodulation. This study provides a promising nanoplatform with enhanced PT efficacy and amplified PAI for diagnosis and treatment of biofilm infection.

Modular revision strategy with bispherical augments in severe acetabular deficiency reconstruction.

PURPOSE: Reconstruction of severe acetabular deficiency is extremely challenging in total hip arthroplasty (THA) revisions. Novel bispherical augments were designed to fill acetabular bone loss and facilitate restoration of hip center of rotation (HCOR). Current study aims to compare the outcomes of bispherical augments and tantalum augments. METHODS: Between July 2017 and December 2018, bispherical augments (BA group) were implanted in 25 patients (25 hips) and 22 patients (22 hips) underwent porous tantalum augments (TA group) reconstruction in revision THA. Clinical and radiographic results were evaluated for 25 hips in BA group and 20 hips in TA group at the final follow-up. The mean duration of follow-up was 2.9 years (range, 2.2 ~ 3.7) in BA group and 2.9 years (range, 2.3 ~ 3.8) in TA group. RESULTS: Harris hip scores, HCOR, and leg length discrepancy (LLD) correction did not differ between the treatment groups. The bispherical augments were located more closer to the medial-superior part (zone II) of acetabular shell while the majority of tantalum augments were located at the lateral-superior part (zone I) (P = 0.010). More screws were used in the BA group for augment fixation (mean 2.1 vs. 1.3) (P = 0.000). There was no evidence of loosening or migration in all hips. Only one dislocation occurred in BA group and treated with closed reduction, no recurrence of instability up to the final follow-up. CONCLUSION: The clinical and radiological outcomes of bispherical augments were comparable with tantalum augments; this technique was a reliable alternative method in severe acetabular deficiency reconstruction.

Repair of articular cartilage defect using adipose-derived stem cell-loaded scaffold derived from native cartilage extracellular matrix.

The purpose of this study was to investigate the feasibility of adipose-derived stem cells (ADSCs) as the seed cells of cartilage tissue engineering. ADSCs were isolated from adipose tissue that was harvested under sterile conditions from the inguen fold of porcines and cultured in vitro. Acellular cartilage extracellular matrix (ACECM) scaffolds of pigs were then constructed. Moreover, inflammatory cells, as well as cellular and humoral immune responses, were detected using hematoxylin and eosin staining staining, immunohistochemical staining, and western blot analysis. The results showed that the cartilage complex constructed by ADSCs and ACECM through tissue engineering successfully repaired the cartilage defect of the pig knee joint. The in vivo repair experiment showed no significant difference between chondrocytes, ADSCs, and induced ADSCs, indicating that ADSCs do not require in vitro induction and have the potential for chondrogenic differentiation in the environment around the knee joint. In addition, pig-derived acellular cartilage scaffolds possess no obvious immune inflammatory response when used in xenotransplantation. ADSCs may serve as viable seed cells for cartilage tissue engineering.

Notch Signaling in Osteogenesis, Osteoclastogenesis, and Angiogenesis.

Skeletal tissue development and regeneration in mammals are intricate, multistep, and highly regulated processes. Various signaling pathways have been implicated in the regulation of these processes, including Notch. Notch signaling is a highly conserved, intercellular signaling pathway that regulates cell proliferation and differentiation, determines cell fate decision, and participates in cellular process in embryonic and adult tissue. Here, we review recent data showing the regulation of Notch signaling in osteogenesis, osteoclastogenesis, and angiogenesis. These processes are cell-context-dependent via direct or indirect mechanisms. Furthermore, Notch signaling may be highly beneficial for efficient coupling of osteogenesis and angiogenesis for tissue engineering and skeletal repair, which is critical to develop clinically therapeutic options.

Comprehensive Analysis of lncRNA and miRNA Expression Profiles and ceRNA Network Construction in Osteoporosis.

Multiple profiling studies have identified a number of non-coding RNAs associated with the pathogenesis of human diseases. However, the exact regulatory mechanisms and functions of these non-coding RNAs in the development of osteoporosis have not yet been explored. Transcriptome gene expression and miRNA microarray data from peripheral blood monocytes of five high hip bone mineral density (BMD) subjects and five low hip BMD subjects were analyzed. Differentially expressed mRNAs, lncRNAs, and miRNAs were identified and subjected to functional enrichment analysis. Additionally, protein-protein interaction (PPI), lncRNA-mRNA, and mRNA-lncRNA-miRNA competing endogenous RNA (ceRNA) networks were constructed. Differential analysis revealed that 297 mRNAs, 151 lncRNAs, and 38 miRNAs were significantly differentially expressed between peripheral blood monocytes from high and low hip BMD subjects. Key genes including ACLY, HSPA5, and AKT1 were subsequently identified in the PPI network. Additionally, differentially expressed lncRNAs were primarily enriched in the citrate cycle (TCA cycle), biosynthesis of antibiotics, and carbon metabolism pathways. Finally, the mRNA-lncRNA-miRNA network revealed several key ceRNA regulatory relationships among the transcripts and non-coding RNAs. Key mRNAs and non-coding RNAs identified in the networks represent potential biomarkers or targets in the diagnosis and management of osteoporosis. Our findings represent a resource for further functional research on the ceRNA regulation mechanism of non-coding RNA in osteoporosis.

Fully physically cross-linked double network hydrogels with strong mechanical properties, good recovery and self-healing properties.

Combining a hydrophobic interaction crosslinked curdlan as the first network and hydrophobic interaction crosslinked polyacrylamide as the second network, we have fabricated a curdlan/HPAAm double network (DN) hydrogel using a one-pot method. The resulting DN hydrogel exhibited good mechanical properties, i.e. an elastic modulus of 103 kPa, a tensile fracture strength of 0.81 MPa, a tensile stretch of 25.3 and a compressive stress of 62.5 MPa when the compressive strain increased up to 99%. The DN gel could withstand ten compression tests under 90% compressive strain without observable damage. The DN gel demonstrated 84% stiffness recovery and 97% toughness recovery after the deformed samples were relaxed and stored at 95 °C for 4 h. The stiffness and fracture stress of the DN gel were enhanced after sterilization treatment at 120 °C. Furthermore, the gels exhibited 52% self-healing of fracture stretch after the samples were cut and brought into contact at 95 °C for 4 h. The self-recovery and self-healing properties of the DN gel both originated from the first curdlan network via the reformation of hydrophobic interactions and the second HPAAm network via reformation of the broken hydrophobic associations.

Direct anterior approach in lateral position achieves superior cup orientation in total hip arthroplasty: a radiological comparative study of two consecutive series.

INTRODUCTION: Although the advantages of total hip arthroplasty (THA) using the direct anterior approach (DAA) have been well documented, DAA in the supine position is limited by the difficulty in exposing the acetabulum and femur, which may result in implant malpositioning and intra-operative complications. Recent studies have reported that DAA-THA in the lateral position can achieve satisfactory clinical and radiographic outcomes. The aim of this study was to investigate the difference in implant alignment between two patient cohorts that underwent primary THA by DAA and the traditional posterolateral approach (PLA) in the lateral position. METHODS: A total of 208 THAs (110 using DAA and 98 using PLA) were retrospectively analyzed. RESULTS: The cup anteversion angle was closer to the target anteversion angle, and the accuracy of cup orientation was superior in the DAA group. A total of 82 (74.5%) DAA-THA and 56 (57.1%) PLA-THA cases showed successful inclination and anteversion angles (p = 0.008) of the implant. In addition, 90 (81.8%) DAA-THA and 67 (68.4%) PLA-THA cases had successful anteversion angle (p = 0.024). There was no significant difference between the two groups in terms of successful inclination angle (98 vs. 81, p = 0.181), as well as in the stem alignment in both coronal and sagittal planes. CONCLUSION: THA using DAA in the lateral position can achieve superior cup orientation compared to PLA while maintaining the stem alignment.

A Reliable Femoral Osteotomy in Total Hip Arthroplasty for Hartofilakidis Type C Developmental Dysplasia of the Hip: Proximal Femoral Reconstruction.

BACKGROUND: Procedure of the femur is extremely challenging during total hip arthroplasty (THA) for Hartofilakidis type C developmental dysplasia of the hip. The main purpose of this study is to compare the clinical effectiveness of proximal femoral reconstruction (PFR) with subtrochanteric transverse osteotomy (STO). METHODS: Between 2006 and 2015, 33 primary THAs in 26 patients were performed with PFR and 16 hips in 13 patients underwent STO. The mean follow-up was 4.2 (range, 2.2-10.8) years in PFR group and 5.9 (range, 3.5-11.3) years in STO group. At the final follow-up, clinical scores and radiographic results were evaluated for 33 hips in PFR group and 15 hips in STO group. RESULTS: Postoperative Harris hip scores and implant position did not differ between the treatment groups. The mean length of the oblique osteotomy line at proximal femur was 6.9 cm (range, 5.8-7.6 cm) in PFR group. The amount of bone union occurred within 6 months after surgery was 24 (72.7%) hips in PFR group and 9 (60.0%) in STO group. Three major postoperative complications occurred in PFR group, and medial femoral calcar erosion was noted in 1 hip in STO group. CONCLUSION: Similar with STO, the clinical results of PFR technique are a reliable solution for femoral procedure during THA in patients with Hartofilakidis type C developmental dysplasia of the hip.

Percutaneous endoscopic lumbar discectomy and microsurgical laminotomy : A prospective, randomized controlled trial of patients with lumbar disc herniation and lateral recess stenosis.

BACKGROUND: Sufficient decompression of the nerve root canal is still regarded as the method of choice when operating on patients with lumbar disc herniation (LDH) with lumbar lateral recess stenosis; however, tissue-sparing procedures are becoming more popular. Endoscopic techniques offer advantages and the benefits of rehabilitation, which have become the standard in many surgical operations when operating on the spine. A significant issue has been the upgrading of instruments to provide enough bone resection under continuous visual control. MATERIAL AND METHODS: We examined patients who had LDH with lateral recess stenosis and compared the results of nerve root canal decompression using percutaneous endoscopic lumbar discectomy (PELD) with a microsurgical laminotomy (ML) technique. In this study 40 patients with full endoscopic decompression or microsurgery were followed up for 2 years. In addition to general and specific parameters, the following two parameters were also used for the investigation: the Visual Analog Scale (VAS) and the Oswestry Disability Index (ODI). RESULTS: Except for 1 patient in whom repair was done by fusion and 1 who was lost to follow-up, 38 patients remained in the study over the 2 years. The mean operating time in the PELD group was longer (p < 0.05), but intraoperative and postoperative blood loss was less than in the ML group (p < 0.05). The postoperative results were better than before surgery, and the VAS and ODI parameters indicated a clear improvement in leg pain and daily activities in both groups (p > 0.05). Of the patients three suffered increasing back pain (2 ML, 1 PELD). CONCLUSION: The results indicated that the PELD can provide an effective supplement and serve as an alternative for LDH with lateral recess stenosis compared with the ML technique when the indication criteria are fulfilled. The PELD also has the advantage of being a minimally invasive intervention.

Notch activation promotes osteoblast mineralization by inhibition of apoptosis.

Notch activator Jagged1 (JAG1) plays a critical role in the regulation of osteoblast differentiation and bone metabolism. In this study, JAG1-induced osteoblast proliferation, differentiation, and mineralization has been analyzed in primary osteoblasts for up to 7 days. Alkaline phosphatase and Alizarin red staining showed an enhanced osteoblast maturation and mineralization in JAG1 treated cells, as well as higher mRNA levels of late osteoblast differentiation markers. In contrast, Notch inhibitor DAPT and deletion of Runx2 totally blocked JAG1 effects on osteoblast mineralization. Flow cytometry data further showed a significantly higher cell proliferation in early stages of culture at day 3, and lower levels of osteoblast apoptosis in late stages of culture at day 7. More importantly, activation of anti-apoptotic factor BCL-2 was enhanced, while pro-apoptotic factor Caspase3 was reduced in JAG1 treated osteoblasts. Therefore, we conclude that cell mineralization is enhanced via anti-apoptotic actions of Notch signaling within the osteoblast cells.

Chondroprotective Effects of Hyaluronic Acid-Chitosan Nanoparticles Containing Plasmid DNA Encoding Cytokine Response Modifier A in a Rat Knee Osteoarthritis Model.

BACKGROUND/AIMS: Interleukin (IL)-1ß plays an essential role in the pathophysiology of osteoarthritis (OA). Cytokine response modifier A (CrmA) can prevent the generation of active IL-1ß. This study aimed to explore the chondroprotective effects of hyaluronic acid-chitosan nanoparticles containing plasmid DNA encoding CrmA (HA/CS-CrmA) in a rat OA model. METHODS: HA/CS-CrmA nanoparticles were synthesized through the complex coacervation of cationic polymers. The characteristics, toxicity, and transfection of the nanoparticles were investigated. Furthermore, the potential effects of HA/CS-CrmA nanoparticles were evaluated via a rat anterior cruciate ligament transection (ACLT) model of OA. Cartilage damage and synovial inflammation were assessed by safranin O/fast green and hematoxylin and eosin staining. Type II collagen in cartilage was measured by immunohistochemistry, and the expression levels of IL-1ß, matrix metalloproteinase (MMP)-3, and MMP-13 in synovial tissue were detected by western blot. RESULTS: The HA/CS-CrmA nanoparticles, which effectively entrapped plasmid DNA, showed an adequate size (100-300 nm) and a regular spherical shape. The nanoparticles safely transfected synoviocytes and released plasmid DNA in a sustained manner over 3 weeks. Additionally, HA/CS-CrmA nanoparticles significantly inhibited cartilage damage, synovial inflammation, and the loss of type II collagen induced by ACLT. The expression levels of IL-1ß, MMP-3, and MMP-13 in synovial tissue were dramatically down-regulated by HA/CS-CrmA nanoparticles. CONCLUSIONS: These results suggested that HA/CS-CrmA nanoparticles could attenuate cartilage destruction and protect against early OA by inhibiting synovial inflammation via inhibition of IL-1ß generation.

Effect of arthroscopic resection for discoid lateral meniscus on the axial alignment of the lower limb.

PURPOSE: This study was designed to investigate the changes in the lower limb axial alignment and knee joint function after arthroscopic resection of discoid lateral menisci. METHODS: Pre-operative and post-operative full-length weight-bearing radiographs of the lower limb were obtained from 60 patients with discoid lateral menisci from August 2015 to August 2016. Twenty-four patients were treated with meniscectomy and 36 cases were treated with meniscoplasty. The axial alignment of the lower limb was measured, and changes in the lower limb axial alignment before and after surgery were analyzed. The effects of differing degrees of meniscal resection on the lower limb axial alignment were compared and analyzed. Knee joint function on the affected side was scored using the Lysholm knee scoring, Tegner activity, and International Knee Documentation Committee (IKDC) subjective scales before surgery and one, six and 12 months after surgery. RESULTS: There were apparent changes in the lower limb axial alignment after surgery (p < 0.01). The changes were more conspicuous after a total meniscectomy than a meniscoplasty but were insignificant (p > 0.05). Intragroup comparisons of the Lysholm knee, IKDC, and Tegner scores before and after surgery revealed significant differences (p < 001). However, the differences were not significant between the two surgical approaches (p > 0.05). CONCLUSION: For those with considerable genu varum or genu valgum after surgery, individualized therapy should be developed to correct the lower limb axial alignment and to prevent articular cartilage degeneration. Arthroscopic resection of a discoid lateral meniscus greatly improves knee joint function.

A new method to precisely control the depth of percutaneous screws into the pedicle by counting the rotation number of the screw with low radiation exposure: technical note.

STUDY DESIGN: Technique note. OBJECTIVES: To report a new method for precisely controlling the depth of percutaneous pedicle screws (PPS)-without radiation exposure to surgeons and less fluoroscopy exposure to patients than with conventional methods. PPS is widely used in minimal invasive spine surgery; the advantages include reduced muscle damage, pain, and hospital stays. However, placement of PPS demands repeated checking with fluoroscopy. Thus, radiation exposure is considerable for both surgeons and patients. METHODS: The PPS depth was determined by counting rotations of the screws. The distance between screw threads can be measured for particular screws; thus, full rotations of the PPS results in the screw advancing in the pedicle the distance between screw threads. To fully insert screws into the pedicle, the number of full rotations is equal to the number of threads in the PPS. RESULTS: We applied this technique in 58 patients with thoracolumbar fracture. The position and depth of the screws was checked during the operation with the C-arm and after operation by anteroposterior X-ray film or computed tomography. No additional procedures were required to correct the screws; we observed no neurological deficits or malpositioning of the screws. In the screw placement procedure, the radiation exposure for surgeons is zero, and the patient is well protected from extensive radiation exposure. CONCLUSIONS: This method of counting rotation of screws is a safe way to precisely determine the depth of PPS in the placement procedure. LEVEL OF EVIDENCE: IV.

Direct Anterior Approach for Total Hip Arthroplasty in the Lateral Decubitus Position: Our Experiences and Early Results.

BACKGROUND: The direct anterior approach (DAA) for total hip arthroplasty (THA) is typically performed in the supine position using a specially designed operating room table, which makes this approach more accessible to orthopedic surgeons. We attempted to perform this procedure in the lateral decubitus position on an ordinary operation table to avoid dependence on a special operating room table. There is an obvious absence of literature regarding this subject. METHODS: A total of 248 patients (295 hips) were recruited for primary THAs from July 1, 2014 to December 31, 2014. In total, 126 hips (42.7%) underwent THAs using the DAA in the lateral decubitus position. The technical feasibility and early results were evaluated. RESULTS: The orientation of the acetabular component was 16.5° ± 4.9° anteversion and 43.3° ± 3.5° abduction. Intraoperative proximal femoral fracture occurred in one hip. The superficial wound complications occurred in 2 hips and the hematoma in one hip while in hospital. The lateral femoral cutaneous nerve injury was noted in 43 hips. The early dislocation occurred in 2 hips. Heterotopic ossification was Brooker class I in 5 hips and class II in 1 hip. No aseptic loosening, postoperative periprosthetic fracture, and deep infection occurred in our series. CONCLUSION: The DAA for THA in the lateral decubitus position may be a valuable alternative if the DAA in the supine position is difficult to implement owing to absence of a special operating room table. This technique also seems to provide satisfactory clinical and radiographic outcomes with an acceptable complication in our early follow-up.

High-level expression of periostin is significantly correlated with tumour angiogenesis and poor prognosis in osteosarcoma.

Periostin (PN), originally named as osteoblast-specific factor-2 (OSF-2), has been involved in regulating adhesion and differentiation of osteoblasts. Recently many studies have shown that high-level expression of PN is correlated significantly with tumour angiogenesis and prognosis in many kinds of human cancer. However, whether and how periostin expression influences prognosis in osteosarcoma remains unknown. This study aimed to examine the expression of PN in patients with osteosarcoma and explore the relationship of PN expression with clinicopathologic factors, tumour angiogenesis and prognosis. Immunohistochemistry was performed to determine the expression of PN in osteosarcoma and osteochondroma respectively. Vascular endothelial growth factor (VEGF) and CD34 were also examined in tissues from the osteosarcoma patients mentioned above. The results showed that PN expression was significantly (P < 0.05) higher in osteosarcoma (80.9%) than in osteochondroma (14.7%). Increased PN protein expression was associated with histological subtype (P = 0.000), Enneking stage (P = 0.027) and tumour size (P = 0.009). The result also showed that high expression of PN correlated with VEGF expression (r = 0.285; P = 0.019) and that tumours with PN-positive expression significantly had higher microvessal density (44.6 ± 13.7 vs. 20.6 ± 6.5; P = 0.000) compared to those in normal bone tissues. Additionally, the expression of PN was found to be an independent prognostic factor in osteosarcoma patients. In conclusion, our findings suggest that PN may have an important role in tumour progression and may be used as a prognostic biomarker for patients with osteosarcoma.

Cementless Total Hip Arthroplasty With a High Hip Center for Hartofilakidis Type B Developmental Dysplasia of the Hip: Results of Midterm Follow-Up.

BACKGROUND: Acetabular reconstruction in adults with Hartofilakidis type B developmental dysplasia of the hip is a major technical challenge. The purpose of this retrospective study was to evaluate hip function and radiographic outcomes regarding high hip center at midterm follow-up. METHODS: From January 1, 2007 to December 31, 2009, 37 patients who had Hartofilakidis type B developmental dysplasia of the hip underwent a primary total hip arthroplasty using a high hip center technique. Functional, radiographic, and survivorship outcomes were evaluated. RESULTS: Of the 37 patients, 31 patients (83.8%) were available for the mean follow-up of 6.1 years (range, 1.5-7.6 years). Thirty-one cementless cups were located at an average vertical distance of 38.1 ± 3.3 mm and at a mean horizontal distance of 35.5 ± 3.4 mm. The mean ratio of the height of the hip center was 2.4% (range, 2.0%-2.9%). The Harris Hip Scores were improved from 50.3 points (range, 38-63 points) preoperatively to 92.3 points (range, 85-100 points) at the final follow-up (P < .001). Four patients continued to present with Trendelenburg gait pattern at the last follow-up. With use of revision for any reason and aseptic loosening as the end point, the 5-year survival rates were 90.3% (95% CI, 79.9%-100%) and 93.3% (95% CI, 84.3%-100%), respectively. CONCLUSIONS: The high hip center technique in conjunction with a cementless acetabular component seems to be a valuable alternative to achieve satisfactory midterm outcomes for Hartofilakidis type B developmental dysplasia of the hip.

Surgical treatment for young adult hip dysplasia: joint-preserving options.

Developmental dysplasia of the hip (DDH) is a spectrum of disorders that results in anatomic abnormalities leading to increased contact stress in the joint and, eventually, secondary osteoarthritis. However, many patients with DDH become symptomatic before the severe degenerative changes of the hip because of abnormal hip biomechanics, mild hip instability, impingement, or associated intra-articular pathology. Early diagnosis and appropriate treatment for DDH are of the utmost importance. With the modification of techniques like pelvic osteotomy and capsular arthroplasty, and the introduction of intracapsular procedures such as arthroscopy and femoral head-neck junction osteochondroplasty, many young patients with symptomatic hip dysplasia may benefit from joint preservation procedures. We review the current development of these concepts and the associated surgical techniques.

Ultrasound microbubbles enhance human ß-defensin 3 against biofilms.

BACKGROUND: The infection of orthopedic implantation devices with Staphylococcus has been a serious concern within the biomaterial community. Treatments are not always successful because of antibiotic-resistant bacteria biofilm infection. Recent studies have shown that combination of antibiotics with low-frequency ultrasound (US) can enhance the bactericidal activity effectively against the formation of biofilms in vitro pilot study. Meanwhile, microbubbles evolved as targeted drug-delivery agents can provide nuclei for inertial cavitation and lower the threshold for US-induced cavitation. Human ß-defensin 3 (HBD-3) is a cationic antimicrobial peptide considered particularly promising for future bactericidal employment and has effect on antibiotic-resistant Staphylococcus biofilms. But the effect has not been reported when combined with US-targeted microbubble destruction (UTMD) in vivo. METHODS: In this study, we evaluated the effect of HBD-3 combined with UTMD on two tested Staphylococcus by the spread plate method, crystal violet staining, confocal laser scanning microscopy, scanning electron microscopy, and real-time polymerase chain reaction. RESULTS: In the study, we found that the biofilm densities, the percentage of live cells, and the viable counts of two tested Staphylococcus that recovered from the biofilm on the titanium surface in mice were significantly decreased in the group of the HBD-3 combined with UTMD, compared with those of other groups. Furthermore, in the experiment, we found out that UTMD could enhance HBD-3 activity, which inhibits the biofilm-associated genes expression of icaAD and the methicillin-resistance genes expression of MecA by promoting the icaR expression simultaneously. CONCLUSIONS: The combination of HBD-3 with UTMD can play a significant role on the elimination of the antibiotic-resistant Staphylococcus biofilms in vivo.