Jincheng Wang

A functional chitosan-based hydrogel as a wound dressing and drug delivery system in the treatment of wound healing

Functional active wound dressings are expected to provide a moist wound environment, offer protection from secondary infections, remove wound exudate and accelerate tissue regeneration, as well as to improve the efficiency of wound healing. Chitosan-based hydrogels are considered as ideal materials for enhancing wound healing owing to their biodegradable, biocompatible, non-toxic, antimicrobial, biologically adhesive, biological activity and hemostatic effects. Chitosan-based hydrogels have been demonstrated to promote wound healing at different wound healing stages, and also can alleviate the factors against wound healing (such as excessive inflammatory and chronic wound infection). The unique biological properties of a chitosan-based hydrogel enable it to serve as both a wound dressing and as a drug delivery system (DDS) to deliver antibacterial agents, growth factors, stem cells and so on, which could further accelerate wound healing. For various kinds of wounds, chitosan-based hydrogels are able to promote the effectiveness of wound healing by modifying or combining with other polymers, and carrying different types of active substances. In this review, we will take a close look at the application of chitosan-based hydrogels in wound dressings and DDS to enhance wound healing.

Activated macrophage-targeted dextran–methotrexate/folate conjugate prevents deterioration of collagen-induced arthritis in mice

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, leading to articular synovial hyperplasia, cartilage destruction, and bone erosion. In RA pathophysiology, the activated macrophages contribute to the initiation and maintenance of the disease. Folate receptor, an overexpressed receptor on the activated macrophages, becomes a promising target site for RA treatment. In this work, the folate-modified dextran-methotrexate conjugate (noted as Dex-g-MTX/FA) was synthesized with an untargeted dextran-methotrexate prodrug (referred as Dex-g-MTX) as the control. The two prodrugs self-assembled into spherical micelles with both scales of about 90 nm and exhibited sustained MTX release. Dex-g-MTX/FA exhibited more superior cellular uptake mediated by the folate receptor and higher cytotoxicity toward macrophages activated by lipopolysaccharide (LPS) compared with Dex-g-MTX. Moreover, Dex-g-MTX/FA possessed improved biodistribution at the lesion site and stronger remission of RA through the inhibition of proinflammatory cytokines in comparison with both Dex-g-MTX and free MTX. These results demonstrated that the folate-targeted prodrug, i.e., Dex-g-MTX/FA, is a potential strategy for activated macrophage-targeted therapy of RA.

Anterior clinoid process and the surrounding structures.

Background The anterior clinoid process (ACP) is located close to the optic nerve, internal carotid artery, ophthalmic artery, and can be easily injured in an ACP-related surgery. An anatomical study clearly defining the ACP is of great importance. In addition, computed tomographic (CT) images may be a new tool for the anatomical analysis of ACP compared with the use of a cadaver and skull study, and more data related to ACP can be measured by CT images. Purpose We studied the anatomical structure of ACP and the structures surrounding it to provide information to surgeons for ACP-related surgery. Methods Computed tomography angiographic images of 102 individuals were reviewed. The measurement was performed on coronal, sagittal, and axis planes after multiplanar reformation. The length of ACP and the distance between apex of ACP and sagittal midline were measured in the axial plane; the classification of ACP and the occurrence rate of bone bridge were also viewed in axial plane. The thickness of ACP was measured in sagittal plane. Result In Chinese population, 12.3% of the ACP is gasified, and the pneumatization of ACP has a relationship with the pneumatization of sphenoid sinus. The length and thickness of ACP are similar to that in previous studies in cadaver. The apex of ACP is relatively stationary to the C3 and C4 segments of the internal carotid artery. The occurrence rate of anterior and middle clinoid bone bridge was 7.8%; the occurrence rate of anterior and posterior clinoid bone bridge was 9.3%. Conclusions The anatomical structure of ACP can be studied effectively in CT images. Recognizing the anatomical characteristics of the ACP and optic strut is important in decreasing the incidence of surgical complications of an anterior clinoidectomy and in the proper intraoperative management to prevent these complications.

Novel exploration of 3D printed wrist arthroplasty to solve the severe and complicated bone defect of wrist

Purpose Although proximal row carpectomy, wrist arthrodesis and even total wrist arthroplasty were developed to treat wrist disease using bone and cartilage of the wrist, severe and complicated bone defects caused by ferocious trauma and bone tumors remain a stubborn problem for surgeons. Development and application of the three-dimensional (3D) printing technology may provide possible solutions. Design/methodology/approach Computed tomography (CT) data of three cases with severe bone defects caused by either trauma or bone tumor were collected and converted into three-dimensional models. Prostheses were designed individually according to the residual anatomical structure of the wrist based on the models. Both the models and prostheses were produced using 3D printing technology. A preoperative design was prepared according to the models and prostheses. Then arthroplasty was performed after preoperative simulation with printed models and prostheses. Findings The diameter of the stem and radial medullary cavity, the direction and location of the prosthesis, and other components were checked during the preoperative design and simulation process phases. The three cases with 3D printed wrist all regained reconstruction of normal anatomy and part of the function after surgery. The average increasing Cooney score rate of Cases 2 and 3 was 133.34 ± 23.57 per cent, and that of Case 1 reached 85 per cent. The average declining rate of the Gartland and Werley Score in Cases 2 and 3 was 65.21 ± 18.89 per cent, and that of Case 1 dropped to 5 per cent in the last follow-up. The scores indicated that patients experienced pain relief and function regain. In addition, the degree of patient satisfaction improved. Originality/value 3D printed wrist arthroplasty may provide an effective method for severe and complicated cases without sacrificing other bones. Personal customization can offer better anatomy and function than arthrodesis or other traditional surgical techniques.

5-Fluorouracil loaded thermosensitive PLGA–PEG–PLGA hydrogels for the prevention of postoperative tendon adhesion

Prevention of adhesion after tendon repair surgery is of considerable importance during tendon healing; however, current clinical outcomes are still not fully satisfactory. In this study, thermosensitive 5-fluorouracil (5-Fu) loaded PLGA–PEG–PLGA hydrogels were used as injectable physical barriers for the prevention of tissue adhesion during tendon healing and inhibition of fibroblast proliferation. The 5-Fu-loaded hydrogels showed a sol–gel–precipitation phase transition with increasing temperature, and the hydrogels displayed the maximum storage moduli at around physiological temperature. The sustained release of 5-Fu from the hydrogels lasted over 7 days. The PLGA–PEG–PLGA hydrogels degraded within 4 weeks after subcutaneous injection into rats, and showed acceptable biocompatibility in vivo. The anti-adhesion efficacy of the hydrogels, with or without 5-Fu, during the Achilles tendon healing of rats was evaluated by macroscopic and histological analysis. It was found that the group treated with 5-Fu-loaded hydrogels showed a significant inhibition of adhesion formation when compared to the untreated group or the group treated with the hydrogels only. Therefore, the 5-Fu-loaded injectable hydrogels hold potential as efficient physical barriers for the prevention of adhesion formation during Achilles tendon healing.

Customized Knee Prosthesis in Treatment of Giant Cell Tumors of the Proximal Tibia: Application of 3-Dimensional Printing Technology in Surgical Design

Background We explored the application of 3-dimensional (3D) printing technology in treating giant cell tumors (GCT) of the proximal tibia. A tibia block was designed and produced through 3D printing technology. We expected that this 3D-printed block would fill the bone defect after en-bloc resection. Importantly, the block, combined with a standard knee joint prosthesis, provided attachments for collateral ligaments of the knee, which can maintain knee stability. Material/Methods A computed tomography (CT) scan was taken of both knee joints in 4 patients with GCT of the proximal tibia. We developed a novel technique – the real-size 3D-printed proximal tibia model – to design preoperative treatment plans. Hence, with the application of 3D printing technology, a customized proximal tibia block could be designed for each patient individually, which fixed the bone defect, combined with standard knee prosthesis. Results In all 4 cases, the 3D-printed block fitted the bone defect precisely. The motion range of the affected knee was 90 degrees on average, and the soft tissue balance and stability of the knee were good. After an average 7-month follow-up, the MSTS score was 19 on average. No sign of prosthesis fracture, loosening, or other relevant complications were detected. Conclusions This technique can be used to treat GCT of the proximal tibia when it is hard to achieve soft tissue balance after tumor resection. 3D printing technology simplified the design and manufacturing progress of custom-made orthopedic medical instruments. This new surgical technique could be much more widely applied because of 3D printing technology.

Association of gene variants of transcription factors PPARγ, RUNX2, Osterix genes and COL2A1, IGFBP3 genes with the development of osteonecrosis of the femoral head in Chinese population

The molecular pathogenesis of osteonecrosis of the femoral head (ONFH) has been remained obscure so that its prevalence has been increasing in recent decades. Different transcription factors play critical roles in maintaining the balance between osteogenesis and adipogenesis. However, it has been unclear that the genes variants of the transcription factors exert the effects on the imbalance between steogenesis and adipogenesis during the development of ONFH. Here, we selected the 11SNPs from steogenesis, adipogenesis-specific transcription factors RUNX2, Osterix, and PPARγ genes, chondrogenesis or adipogenesis key factors COL2A1, IGFBP3 genes and analysed the genotypes, alleles, haplotypes and their association with the risk and clinical phenotypes of ONFH through Mass ARRAY® platformin in 200 ONFH patients and 177controls. The patients with ONFH (132 males, 68 females; age: 53.46±11.48yr) were consecutively enrolled at the Department of Orthopedics, the Second Clinical College of Jilin University, from March 2014 to June 2015 and were diagnosed and classified into 10 cases of stage II (5.6%), 54 cases of stage III (30.2%) and 115 cases (64.2%) of stage IV and alcohol-induced (71 cases (39.7%)), idiopathic (64 cases (34.0%)), and steroid-induced osteonecrosis (47 cases (26.3%)) subgroup, respectively. Our results showed that all models of logistical regression analysis, the co-dominants, dominants, and recessives of PPARγrs2920502, significantly associated with the increased risk of ONFH (p=0.004, p=0.013, p=0.016), respectively. Both the minor homozygous CC genotype and the allele C of rs2920502 were evidently correlated with the enhanced risk of ONFH (p=0.005, p=0.0005),respectively. The recessives models of IGFBP3rs2132572 (G/A) as well as RUNX2 rs3763190(G/A) were statistically associated with the higher ONFH risk, p=0.030, p=0.029, respectively; the minor homozygous(AA) of IGFBP3rs2132572 (G/A) was also related to the increased risk of bilateral hips lesions, p=0.039. Moreover, the ages on set of major homozygous(GG) and heterozygous(GT) of COL2A1rs2070739(G/A) were significantly younger than that of the minor homozygous(AA) of the SNP(p=0.008) while the A-T-G-A haplotype of COL2A1 gene revealed significant association with the decreased the risk of bilateral hip lesions, p=0.01, OR:0.258. More important, the serum HDL-c level and the ratio of LDL-c/HDL-c in the ONFH group were significantly decreased and increased compared with those of the control group (p=0.02, p=0.0001), respectively. Particularly, the CC genotype of PPARγ rs2920502 was statistically correlated with the enhanced serum TG level, p=0.011.These results suggest that the variants of PPARγ, RUNX2, COL2A1, and IGFBP3 genes closely associated with the development of ONFH.

Validation of internal reference genes for relative quantitation studies of gene expression in human laryngeal cancer.

Background The aim of this study was to determine the expression stabilities of 12 common internal reference genes for the relative quantitation analysis of target gene expression performed by reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) in human laryngeal cancer. Methods Hep-2 cells and 14 laryngeal cancer tissue samples were investigated. The expression characteristics of 12 internal reference gene candidates (18S rRNA, GAPDH, ACTB, HPRT1, RPL29, HMBS, PPIA, ALAS1, TBP, PUM1, GUSB, and B2M) were assessed by RT-qPCR. The data were analyzed by three commonly used software programs: geNorm, NormFinder, and BestKeeper. Results The use of the combination of four internal reference genes was more appropriate than the use of a single internal reference gene. The optimal combination was PPIA + GUSB + RPL29 + HPRT1 for both the cell line and tissues; while the most appropriate combination was GUSB + RPL29 + HPRT1 + HMBS for the tissues. Conclusions Our recommended internal reference genes may improve the accuracy of relative quantitation analysis of target gene expression performed by the RT-qPCR method in further gene expression research on laryngeal tumors.

Heat treatment effect on the mechanical properties, roughness and bone ingrowth capacity of 3D printing porous titanium alloy

The weak mechanical strength and biological inertia of Ti–6Al–4V porous titanium alloy limit its clinical application in the field of orthopedics. The present study investigated the influence of different solution temperatures (e.g. 800 °C, 950 °C and 1000 °C) on the mechanical properties, roughness and bone ingrowth capacity of Ti–6Al–4V porous titanium alloy prepared by Electron Beam Melting. It was found that the compressive and shear strength were promoted with the increase of solution temperature because of the transformed crystallinity of Ti–6Al–4V titanium alloy and phase changes from TiAl to TiAl + TiV. In addition, the topological morphology, surface roughness and wettability of the porous titanium alloy scaffolds were improved after heat treatment, and in turn, the adhesion rate and cell proliferation of bone marrow mesenchymal stem cells were enhanced. Compared with the scaffolds before and after heat treatment at 800 °C, the scaffolds heat-treated at 950 °C and 1000 °C achieved better bone ingrowth, extracellular matrix deposition and osseointegration. These findings indicate the great potential of heat treatment in possessing Ti–6Al–4V porous titanium alloy for orthopedic implant.

Chitosan-Based Scaffolds for Cartilage Regeneration

Intra-joint trauma often accompanies cartilage damage, as one of the main reasons of osteoarthritis, which often induce severe pain and limited joint function in the final stage. Because of the poor regenerative capacity, cartilage repair has been on the top list of regenerative medicine from decades ago. Recently, the researches of cartilage regeneration are mainly focused on the development of novel scaffolds, which can provide spatial frame and logistic template for stem cells, other progenitor cells, or chondrocytes to proliferate or differentiate into cartilage-like tissues. Among the dazzling scaffolds, chitosan-based systems, including physical hydrogels, chemically cross-linked hydrogels, or porous scaffolds, show great potential in cartilage tissue regeneration. Chitosan possesses superior characteristics, such as biocompatibility, biodegradability, bioabsorbability, low immunogenicity, and intrinsic antibacterial nature, for potential applications in tissue engineering. Specially, the chemical structure of chitosan is similar with various glycosaminoglycans (GAGs), which play important roles in chondrocyte morphology modulation, differentiation, and function. In addition, appropriate mechanical properties and porosity, excellent cell adhesion, and even control release of functional growth factors are achieved in chitosan-based scaffolds. In this chapter, the advancements of different types of chitosan-based scaffolds for cartilage regeneration are systemically summarized, and the future directions are predicted.