A comparison of biomechanical changes on femoral head following rotational acetabular osteotomy and eccentric rotational acetabular osteotomy in normal cadaveric hip.

PURPOSE: Both rotational acetabular osteotomy (RAO) and eccentric rotational acetabular osteotomy (ERAO) are effective procedures for young patients with developmental dysplasia of the hip. However, no comparative study of biomechanical changes has been reported following these two procedures. We therefore explored the stress changes on femoral head after RAO and ERAO under different load conditions. MATERIALS AND METHODS: Twelve female cadaveric hips without deformity were divided into RAO group and ERAO group. Stress value on femoral head was measured preoperatively and postoperatively after the vertical force was loaded on the cadaveric spine from 0 to 500 N. Stress change value was then calculated base on the measurements. RESULTS: In the RAO group, preoperative stress increased when loading on spine became larger, but postoperative stress changed its increasing trend into decreasing when the load was greater than 200 N (turning point). Same phenomenon was found in the ERAO group (turning point was 300 N). However, the difference between preoperative and postoperative stress was not statistically significant in both RAO and ERAO groups. Stress change value from each procedure showed similar trends. With the load growth, stress change increased firstly and then decreased, but the difference between RAO and ERAO was not statistically significant. CONCLUSIONS: Both RAO and ERAO could correct the abnormal biomechanical effect of dysplastic hip; moreover, they may have similar biomechanical effects on femoral head, obtaining the same clinical outcomes. Non-biomechanical factors (surgical trauma, technical complexity, etc.) also play important roles in procedure selection.

Presence of interleukin-17C in the tissue around aseptic loosened implants.

PURPOSE: The most common long-term complication of joint arthroplasty is aseptic loosening. The proinflammatory cytokines secreted by macrophages are involved in aseptic loosening. Recently, a novel proinflammatory cytokine IL-17C was reported to participate in inflammatory diseases by synergising with proinflammatory cytokines. However, the relationship between IL-17C and the aseptic loosening is unclear. METHODS: The tissues around aseptic loosened implants were collected during revision surgery and handled by formalin fixation and embedded in paraffin. The presence of IL-17C in the tissues around the aseptic loosened implants was investigated in 12 aseptic loosening patients using immunofluorescence. RESULTS: The presence of IL-17C protein in the tissues around aseptic loosened implants was detected by immunofluorescence. There are no statistical differences between optical density of IL-17C in aseptic loosening samples and in rheumatoid arthritis samples (positive control). CONCLUSIONS: These results suggest the presence of IL-17C in aseptic loosening. Interleukin-17C was related to the inflammation of aseptic loosening, possibly by contributing to the inflammation and osteolysis in the tissues surrounding aseptic loosened implants.

Bio-functional hydrogel with antibacterial and anti-inflammatory dual properties to combat with burn wound infection.

Burn infection delays wound healing and increases the burn patient mortality. Consequently, a new dressing with antibacterial and anti-inflammatory dual properties is urgently required for wound healing. In this study, we propose a combination of methacrylate gelatin (GelMA) hydrogel system with silver nanoparticles embed in γ-cyclodextrin metal-organic frameworks (Ag@MOF) and hyaluronic acid-epigallocatechin gallate (HA-E) for the burn wound infection treatment. Ag@MOF is used as an antibacterial agent and epigallocatechin gallate (EGCG) has exhibited biological properties of anti-inflammation and antibacterial. The GelMA/HA-E/Ag@MOF hydrogel enjoys suitable physical properties and sustained release of Ag+. Meanwhile, the hydrogel has excellent biocompatibility and could promote macrophage polarization from M1 to M2. In vivo wound healing evaluations further demonstrate that the GelMA/HA-E/Ag@MOF hydrogel reduces the number of the bacterium efficiently, accelerates wound healing, promotes early angiogenesis, and regulates immune reaction. A further evaluation indicates that the noncanonical Wnt signal pathway is significantly activated in the GelMA/HA-E/Ag@MOF hydrogel treated group. In conclusion, the GelMA/HA-E/Ag@MOF hydrogel could serve as a promising multifunctional dressing for the burn wound healing.

3D-printed dermis-specific extracellular matrix mitigates scar contraction via inducing early angiogenesis and macrophage M2 polarization.

Scar contraction frequently happens in patients with deep burn injuries. Hitherto, porcine dermal extracellular matrix (dECM) has supplied microenvironments that assist in wound healing but fail to inhibit scar contraction. To overcome this drawback, we integrate dECM into three-dimensional (3D)-printed dermal analogues (PDA) to prevent scar contraction. We have developed thermally gelled, non-rheologically modified dECM powder (dECMp) inks and successfully transformed them into PDA that was endowed with a micron-scale spatial structure. The optimal crosslinked PDA exhibited desired structure, good mechanical properties as well as excellent biocompatibility. Moreover, in vivo experiments demonstrated that PDA could significantly reduced scar contraction and improved cosmetic upshots of split thickness skin grafts (STSG) than the commercially available dermal templates and STSG along. The PDA has also induced an early, intense neovascularization, and evoked a type-2-like immune response. PDA's superior beneficial effects may attribute to their desired porous structure, the well-balanced physicochemical properties, and the preserved dermis-specific ECM cues, which collectively modulated the expression of genes such as Wnt11, ATF3, and IL1ß, and influenced the crucial endogenous signalling pathways. The findings of this study suggest that PDA is a clinical translatable material that possess high potential in reducing scar contraction.

Lateral epicondyle osteotomy approach for coronal shear fractures of the distal humerus: Report of three cases and review of the literature.

BACKGROUND: Coronal shear fractures of the distal humerus are rare injuries and are technically challenging to manage. Open reduction and internal fixation (ORIF) has become the preferred treatment because it provides anatomical reduction, stable internal fixation, and early motion, but the optimal surgical approach remains controversial. CASE SUMMARY: We report three cases of coronal shear fractures of the distal humerus treated successfully by ORIF via a novel surgical approach, in which lateral epicondyle osteotomy was performed based on the extended lateral approach. We named the novel surgical approach the lateral epicondyle osteotomy approach. All patients underwent surgical treatment and were discharged successfully. All patients had excellent functional results according to the Mayo elbow performance score. The average range of motion was 118° in flexion/extension and 172° in pronation/ supination. Only case 2 had a complication, which was implant prolapse. CONCLUSION: We demonstrated that the lateral epicondyle osteotomy approach in ORIF is effective and safe for coronal shear fractures of the distal humerus.

An immune-competent rat split thickness skin graft model: useful tools to develop new therapies to improve skin graft survival.

Skin grafting is the routine standard of care to manage third degree burns and problematic skin defects. Several commercially available dermal substitutes and biologic skin equivalents are placed in the wound bed to facilitate the healing process of the skin grafts, as well as to provide mechanical support for the cells to grow and to delay the contracture. To study pathology and develop new therapies, an immune-competent rat model is required. We have created two different skin graft animal models to mimic the clinical skin grafting operation, the dorsum skin grafting (DG) and inguinal skin grafting (IG). To create a recipient site, a full-thickness, round excision wound was created on the dorsum between rats' scapular angles, covered with DG or IG. Graft contraction was quantified and tissue was harvested on predetermined time points for analysis. Histologic staining was performed to differentiate between DG and IG. Collagen deposition was assessed with Masson's trichrome staining. Mast cells were detected with Toluidine blue. Macrophages were stained with CD68 immune. Vascularity was assessed with functional vessels numbers. Cell proliferation was assessed with Ki67 immune. This model has all the advantages of murine models, such as an abundance of genetic variants and applicable tools, low cost, and practical housing techniques, all of which will promote the development of new therapies and testing new biologic skin equivalents and dermal substitutes.

Negatively-charged aerosol improves burn wound healing by promoting eNOS-dependent angiogenesis.

Aerosols exist in the form of liquid or solid particles that stably suspending in air. Our previous studies have found that aerosol can accelerate chronic wound healing. However, the biological effects of aerosol in burn wound healing and the underlying molecular mechanism remain unclear. This study aimed to investigate the effects of aerosol on the healing of deep partial-thickness burn wounds and its regulatory mechanisms. By employing a self-controlled model of rats, we demonstrated that aerosol treatment not only increased the healing rate, but also improved the healing quality of deep partial-thickness burn wounds. Besides, the excessive inflammatory responses in the burn wounds were inhibited, and the angiogenesis was increased after aerosol treatment. It did so by upregulating the expression of eNOS/NO, as well as the VGEF expression during the wound healing process. Our results demonstrate that the function of aerosol in promoting burn wound healing is achieved by activating eNOS/NO pathway.

Epidermal HMGB1 Activates Dermal Fibroblasts and Causes Hypertrophic Scar Formation in Reduced Hydration.

HMGB1 protein is a multifunctional cytokine involved in inflammatory reactions and is known to play a key role in tissue repair and fibrosis. However, the function of HMGB1 in fibrotic skin diseases, such as hypertrophic scar formation, remains unclear. In this study, HMGB1 was detected in the nuclei of epidermal cells in normal skin and had accumulated in the cytoplasm in hypertrophic scars. By establishing a keratinocyte-fibroblast co-culture and conditional medium treatment models, we found that a reduced hydration condition increased the expression and secretion of HMGB1 in keratinocytes, subsequently activating dermal fibroblasts. HMGB1 secreted from keratinocytes activated fibroblasts by promoting the nuclear import of MRTF-A, increased the nuclear accumulation of MRTF-A/SRF complexes and consequently enhanced α-smooth muscle actin promoter activation. Moreover, blockade of advanced glycation end products or Toll-like receptor 2/4 inhibited the fibroblast activation induced by HMGB1. Finally, local delivery of HMGB1 resulted in marked hypertrophic scar formation in rabbit hypertrophic scar models, while HMGB1 blockade exerted a clear anti-scarring effect. Our results indicate that high HMGB1 levels induced by a reduced hydration status play an important role in hypertrophic scar formation, strongly suggesting that HMGB1 is a novel target for preventing scarring.

Pre-vascularization Enhances Therapeutic Effects of Human Mesenchymal Stem Cell Sheets in Full Thickness Skin Wound Repair.

Split thickness skin graft (STSG) implantation is one of the standard therapies for full thickness wound repair when full thickness autologous skin grafts (FTG) or skin flap transplants are inapplicable. Combined transplantation of STSG with dermal substitute could enhance its therapeutic effects but the results remain unsatisfactory due to insufficient blood supply at early stages, which causes graft necrosis and fibrosis. Human mesenchymal stem cell (hMSC) sheets are capable of accelerating the wound healing process. We hypothesized that pre-vascularized hMSC sheets would further improve regeneration by providing more versatile angiogenic factors and pre-formed microvessels. In this work, in vitro cultured hMSC cell sheets (HCS) and pre-vascularized hMSC cell sheets (PHCS) were implanted in a rat full thickness skin wound model covered with an autologous STSG. Results demonstrated that the HCS and the PHCS implantations significantly reduced skin contraction and improved cosmetic appearance relative to the STSG control group. The PHCS group experienced the least hemorrhage and necrosis, and lowest inflammatory cell infiltration. It also induced the highest neovascularization in early stages, which established a robust blood micro-circulation to support grafts survival and tissue regeneration. Moreover, the PHCS grafts preserved the largest amount of skin appendages, including hair follicles and sebaceous glands, and developed the smallest epidermal thickness. The superior therapeutic effects seen in PHCS groups were attributed to the elevated presence of growth factors and cytokines in the pre-vascularized cell sheet, which exerted a beneficial paracrine signaling during wound repair. Hence, the strategy of combining STSG with PHCS implantation appears to be a promising approach in regenerative treatment of full thickness skin wounds.

Wear particles promote endotoxin tolerance in macrophages by inducing interleukin-1 receptor-associated kinase-M expression.

Toll-like receptors (TLRs) recognizing pathogen-associated molecular patterns (PAMP) play a role in local immunity and participate in implant-associated loosening. TLRs-mediated signaling is regulated by interleukin-1 receptor-associated kinase-M (IRAK-M). Our previous studies have proved that IRAK-M is induced by wear particles in macrophages from periprosthetic tissues. In this study, the IRAK-M-related mechanisms were further explored by lipopolysaccharide (LPS) and/or titanium (Ti) particles stimulations and small interfering RNAs (siRNAs). The protein level of IRAK-M was studied using western blotting and tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) levels were measured using ELISA. Results showed that in RAW264.7 cells stimulated by LPS after Ti particle pre-exposure, IRAK-M was slightly changed, compared with LPS stimulation. And levels of TNF-α and IL-1ß in cultures stimulated by LPS first after Ti particle pre-exposure were lower than in the other two groups which were stimulated by LPS with or without Ti particles (p < 0.001), whereas there were no statistic differences between the later two (p > 0.05). The cytokines were lowest in Ti particles alone stimulation. After siRNAs silenced, IRAK-M-deficient cells exhibited increased expression of the cytokines in LPS stimulation after Ti particle pre-exposure and when stimulated with Ti particles alone. Our findings suggest that debris-induced IRAK-M decreases foreign body reactions, but at the same time, the over-expression of IRAK-M may also be detrimental on local intrusion of PAMPs or bacteria, negatively regulates the LPS-induced and TLRs-mediated inflammation and results in immunosuppression in periprosthetic tissue, which may predispose to implant-associated infections.

IRAK-M in macrophages around septically and aseptically loosened hip implants.

The most common long-term complication of joint arthroplasty is loosening, which is mediated by chronic inflammatory cytokines produced by macrophages stimulated by implant-derived debris and eventually bacterial components adherent to such debris. In this study, antiinflammatory interleukin-1 receptor-associated kinase-M (IRAK-M) was studied in macrophages in interface membranes in vivo using immunohistochemical staining and in titanium particle-stimulated macrophages in vitro using reverse transcriptase-polymerase chain reaction. Results show that the interface membranes of septically and aseptically loosened prosthesis express more IRAK-M protein than control membranes from osteoarthritic patient and that IRAK-M mRNA-levels increase upon particle stimulation. These findings suggest that, the upregulation of IRAK-M in macrophages is involved in the local immunosuppression around implants, and may contribute to septic and aseptic implant loosening.