Identification of potentially functional circRNAs and prediction of circRNA-miRNA-mRNA regulatory network in periodontitis: Bridging the gap between bioinformatics and clinical needs.

BACKGROUND AND OBJECTIVE: Periodontitis is a multifactorial chronic inflammatory disease that can lead to the irreversible destruction of dental support tissues. As an epigenetic factor, the expression of circRNA is tissue-dependent and disease-dependent. This study aimed to identify novel periodontitis-associated circRNAs and predict relevant circRNA-periodontitis regulatory network by using recently developed bioinformatic tools and integrating sequencing profiling with clinical information for getting a better and more thorough image of periodontitis pathogenesis, from gene to clinic. MATERIAL AND METHODS: High-throughput sequencing and RT-qPCR were conducted to identify differentially expressed circRNAs in gingival tissues from periodontitis patients. The relationship between upregulated circRNAs expression and probing depth (PD) was performed using Spearman's correlation analysis. Bioinformatic analyses including GO analysis, circRNA-disease association prediction, and circRNA-miRNA-mRNA network prediction were performed to clarify potential regulatory functions of identified circRNAs in periodontitis. A receiver-operating characteristic (ROC) curve was established to assess the diagnostic significance of identified circRNAs. RESULTS: High-throughput sequencing identified 70 differentially expressed circRNAs (68 upregulated and 2 downregulated circRNAs) in human periodontitis (fold change >2.0 and p < .05). The top five upregulated circRNAs were validated by RT-qPCR that had strong associations with multiple human diseases, including periodontitis. The upregulation of circRNAs were positively correlated with PD (R = .40-.69, p < .05, moderate). A circRNA-miRNA-mRNA network with the top five upregulated circRNAs, differentially expressed mRNAs, and overlapped predicted miRNAs indicated potential roles of circRNAs in immune response, cell apoptosis, migration, adhesion, and reaction to oxidative stress. The ROC curve showed that circRNAs had potential value in periodontitis diagnosis (AUC = 0.7321-0.8667, p < .05). CONCLUSION: CircRNA-disease associations were predicted by online bioinformatic tools. Positive correlation between upregulated circRNAs, circPTP4A2, chr22:23101560-23135351+, circARHGEF28, circBARD1 and circRASA2, and PD suggested function of circRNAs in periodontitis. Network prediction further focused on downstream targets regulated by circRNAs during periodontitis pathogenesis.

Injectable photo crosslinked enhanced double-network hydrogels from modified sodium alginate and gelatin.

Recently, photocrosslinked hydrogels have attracted more and more attention in biomedical applications. In this study, a serials of injectable hydrogels were fabricated from aldehyde methacrylate sodium alginate and amino gelatin (AMSA/AG) using a two-step process. Here, sodium alginate, a kind of natural polysaccharide, was modified by oxidizer to form aldehyde sodium alginate (ASA), and methacrylate groups were further grafted on the main chain of ASA. Gelatin, the denatured form of collagen, was modified with ethylenediamine (ED) to graft more amino groups. When AMSA and AG aqueous solutions were mixed, the Schiff base reaction occurred quickly to form the primary network between aldehyde groups in AMSA and amino groups in AG, and then a 365nm ultraviolet (UV) light was used to initiate the radical reaction of methacrylate groups in AMSA to produce the secondary network. The structures and properties of AMSA/AG hydrogels were evaluated by Fourier Transforms Infrared spectroscopy (FTIR) and 1HNMR analysis. The swelling ratio confirmed the density of crosslinked networks, and the mechanical performance demonstrated that the UV initiated the double crosslinking network hydrogels have an improved mechanical properties compared to the single Schiff base networks hydrogels. The results showed that the photocrosslinked double network hydrogels have enhanced mechanical properties, good biocompatibility and controllable degradation rate. So, this hydrogels may have great potential utilized in regenerative medicine as therapeutic materials.

Modified alginate and gelatin cross-linked hydrogels for soft tissue adhesive.

Soft tissue adhesives made from natural hydrogel are attractive in clinical applications due to their excellent properties, such as high water content, good biocompatibility, low immune, good biodegradability. Hydrogels derived from natural polysaccharides and proteins are ideal components for soft tissue adhesive since they resemble the extracellular matrices of the tissue composed of various sugar and amino acids-based macromolecules. In this paper, a series of novel tissue adhesives mixed by aldehyde sodium alginate (ASA) with amino gelatin (AG) were developed and characterized. The effect of aldehyde content in ASA and amino group content in AG on the properties of ASA/AG cross-linked hydrogel was measured. The results showed the gelling time, swelling behavior and the bonding strength of the hydrogel can be tuned by varying the content of aldehyde groups in ASA and the content of amino groups in AG. The gelation time could be controlled within 4-18 min. When the aldehyde content of ASA is 75.24% and the amino content of AG is 0.61 mmol/g, the hydrogel almost has the adhesive strength equal to the commercially available adhesive fibrin glue. So, this tunable ASA/AG hydrogels in this study could be a promising candidate as soft tissue adhesive and have a wide range of biomedical applications.

[PROGRESS OF ALGINATE DERIVATIVES BASED ON BIOMEDICAL MATERIALS].

OBJECTIVE: To summarize the current research status of alginate derivatives based on biomedical materials, and analyze several key points as novel clinical products. METHODS: The general preparation and application methods of alginate derivatives based on biomedical materials at home and abroad were reviewed. The present status and problems were analyzed. RESULTS: The derivation methods to prepare alginate derivatives include crosslink, sulfation, biological factors derivatization, hydrophobic modification, and graft copolymerization. With excellent bionic performance of structure and properties, many alginate derivatives are available for tissue engineering scaffolds, artificial organs, and drug delivery systems etc. However, more systematic applied basic research data should be collected and statistically analyzed for risk managements. CONCLUSION: Alginate derivatives have good feasibility as novel medical products, meanwhile, systematic evaluation and verification should be executed for their safety, effectiveness, and suitability.

[Research on carboxymethyl chitosan acting as the adjuvant for implantable degradable microspheres].

As a kind of biomaterial, carboxymethyl chitosan (CMC) has excellent biodegradable and bioacceptable capabilities using. This study was aimed to probe into the feasibility of CMC to prepare the implantable sustained release Ciprofloxacin Hydrochloride (CPX) microspheres(MS), and to go further into the pharmaceutic technology, the morphology and the characteristics of in vitro release of the microspheres. First, we prepared the microspheres by emulsification and cross-linking technology. Then, scanning electron microscopy (SEM), infrared spectrum (IR) and differential thermal analysis (DTA) were used to detect the structure and morphology of the MS. The in vitro release of CPX/CMC-MS and the CPX content of the MS were detected through continuous-flow releasing system. We found that the structure and morphology of the MS were affected by the conditions of preparation such as emulsification and cross-linking temperature, ionic strength and stirring speed, that the releasing time of CPX was more than 7 days, and that the releasing behaviors of the microspheres conformed to the Higuchi model. So we drew the conclusions that CMC could be used as a kind of absorbable and implantable adjuvant for sustained release, the technology of emulsification and cross-linking was proved to be feasible, stable and simple.

[Progress of alginate-based biomedical materials].

OBJECTIVE: To review the current situation of alginate-based biomedical materials, especially focus on the clinical strategies and research progress in the clinical applications and point out several key issues that should be concerned about. METHODS: Based on extensive investigation of domestic and foreign alginate-based biomedical materials research and related patent, literature, and medicine producted, the paper presented the comprehensive analysis of its research and development, application status, and then put forward several new research directions which should be focused on. RESULTS: Alginate-based biomedical materials have been widely used in clinical field with a number of patients, but mainly in the fields of wound dressings and dental impression. Heart failure treatment, embolization, tissue engineering, and stem cells culture are expected to become new directions of research and products development. CONCLUSION: Development of alginate-based new products has good clinical feasibility and necessity, but a lot of applied basic researches should be carried out in the further investigations.

[Product standard and quality control of sodium hyaluronate].

OBJECTIVE: To analyze and compare the domestic quality standard and foreign quality standard of sodium hyaluronate (HA), and to expatiate on the critical process monitoring parameters. METHODS: Different quality standards of HA were compared by translating and sorting, and some experimental data were analyzed as well as the manufacturing practice was elaborated. RESULTS: Differences exist in raw materials standard or specifications of products between domestic and foreign, but the basic control points are concordant. CONCLUSION: The company should set up reasonable and controllable quality standard based on quality requirements and related process characteristics so as to assure the safety and effectiveness of the clinical application.

[Properties, products, and applications of chitosan].

OBJECTIVE: To review and analyze the properties, products, and applications of chitosan so as to explore the key molecular structure parameters which can affect the properties and applications significantly, and to reveal the relationship between molecular structures and properties so as to provide reference for further development of chitosan industry and scientific research. METHODS: Based on the collection and analysis of related literature, patents and medical products derived from chitosan, as well as the author's experiences in research and development, evaluation and standardization of chitosan, the paper was prepared to bring more attentions into the correlativity between structure and properties of chitosan. RESULTS: Potential risks in clinical application of chitosan-based preparations were seriously proposed in addition to a scientific review and analysis on relationships between chitosan structure and properties, as well as the present situations of developments and applications of chitosan. CONCLUSION: The molecular structure is the crucial factor that can bring not only positive but also passive effects to the properties and applications of chitosan, especially for highly purified chitosan, molecular weight, and deacetylation degree are the most important parameters that should be focused more attention on.

A thermosensitive chitosan-based hydrogel barrier for post-operative adhesions' prevention.

Post-operative peritoneal adhesions are common and serious complications for surgeons. They can cause pelvic pain, infertility, and potentially lethal bowel obstruction. We synthesized injectable hydrogels that formed by chemical modification through grafted hydrobutyl groups to chitosan chains. Gelation of hydroxybutyl chitosan (HBC) occurs in less than 60 s. Once formed, it can also be recovered completely. The residue time of hydrogels can extend to 4 weeks in Kunming mice. HBC hydrogels showed mild cytotoxicity to mice fibroblast cell (L929) and human vascular endothelial cell (ECV-304) in vitro and were biocompatible in the murine muscles, causing no adhesions for 4 weeks. HBC gels can form a durable barrier between defected cecum and abdominal wall. In a mice sidewall defect-bowel abrasion model, HBC gels showed significant efficacy in reducing adhesion formation.

[Fibrin-based biomaterials for medical device].

OBJECTIVE: To broaden the clinical uses of fibrin-based biomaterials and to develop further study in cell biology and to comprehensively understand and master related knowledge with regard to the present development status of fibrin. METHODS: Many relevant domestic and international papers were reviewed to make a summary. RESULTS: Recognization was obtained from four aspects, which were structure and function of fibrinogen, clinical use of fibrin, fibrin scaffold for tissue engineering, and compounding biomaterials of fibrin. It showed that every aspect had great research extension and practical application. CONCLUSION: Besides a surgical hemostat and sealant, fibrin has great potentials in playing roles of tissue engineering scaffold, drug delivery vehicle, and compounding material.

Feasibility study of chitosan as intravitreous tamponade material.

BACKGROUND: Chitosan can inhibit fibroblastic proliferation by suppressing fibroblast cells, and has the similar physiological characteristics as normal vitreous body, so it might have the potential to become vitreous filling material and might possibly inhibit proliferative vitreous retinopathy. To investigate the possibility of chitosan as vitreous filling material, this study was designed to investigate retina, ciliary body, lens and cornea morphology changes, intraocular pressure and intraocular inflammatory factors fluctuating after chitosan intravitreous tamponade. METHODS: Fifteen healthy chinchilla rabbits were chosen; three of them were a blank (negative) control group without any surgical procedure. The remaining 12 rabbits received vitrectomy on both eyes; all the right eyes (experimental group) were given 1.2-1.8 ml (average 1.5 ml) of chitosan intravitreously, while sodium hyaluronate were given in the left eyes (control group). All eyes underwent slit-lamp biomicroscope and indirect ophthalmoscope examination and intraocular pressure measurement pre- and post-op. The concentration of IL-6, IL-8 (radioimmunoassay), NO (nitrate reductase method) in aqueous humor and vitreous body were tested at day 15 and day 30 post-op. At day 30 post-op, the cornea, ciliary body, and lens were dissected for light microscopy examination, and the retinal tissues 2PD away from the optic disc on the vertical orientation of posterior pole were dissected for light- and electro-microscope examination. RESULTS: The conjunctival congestion and slight inflammatory response in the anterior chamber disappeared within 7 days post-op. During the 30-day experiment, cornea, lens and the filling material in vitreous cavity were transparent in all animals. The retina was attached without proliferation. The intraocular pressure in the experimental group post-op fluctuated between 4.55 +/- 2.94 and 6.25 +/- 2.37 mmHg, which was not significantly different from the situation pre-op (6.18 +/- 1.19 mmHg) (P > 0.05). The intraocular pressure in the control group post-op fluctuated between 5.10 +/- 2.51 and 5.90 +/- 2.49 mmHg, which was not significantly different from the situation pre-op (6.50 +/- 0.94 mmHg) (P > 0.05). There was also no significant difference in the intraocular pressure post-op at different time points between the experimental group and control group (all P > 0.05). At day 15 post-op, IL-6 concentration in aqueous humor were 37.31 +/- 8.59 ng/ml and 39.52 +/- 9.69 ng/ml in experimental group and control group respectively, both higher than those in the blank control group (26.55 +/- 9.34 ng/ml) (P < 0.05). IL-8 concentration were 7.00 +/- 3.79 ng/ml and 6.32 +/- 3.68 ng/ml respectively, no significant difference to the blank control group (4.72 +/- 1.71 ng/ml) (P > 0.05): the concentrations of NO were 63.94 +/- 26.80 micromol/ml and 51.81 +/- 13.19 micromol/ml respectively, no significant difference to the blank control group (50.36 +/- 15.67 micromol/ml) (P > 0.05). At day 30 post-op, the concentrations of IL-6, IL-8 and NO in aqueous humor showed no significant difference among all three groups (P > 0.05). In vitreous body at day 30 post-op, the concentrations of IL-8 in experimental group and control group were 10.17 +/- 3.63 ng/ml and 10.69 +/- 3.52 ng/ml, and those of NO were 50.23 +/- 19.69 micromol/mL and 50.60 +/- 12.72 micromol/mL respectively, all higher than in the blank control group (30.37 +/- 14.63 micromol/ml) (P < 0.05); the concentrations of IL-6 were 24.51 +/- 10.71 ng/ml and 26.36 +/- 13.00 ng/ml, no significant difference to the blank control group (24.06 +/- 5.98 ng/ml) (P > 0.05). At various time points, there was no significant difference in the concentrations of IL-6, IL-8 and NO in aqueous humor and vitreous body in the experimental group and the control group (P > 0.05). There was no morphological change found under light microscopy in cornea, ciliary body and lens. The outer plexiform layer of retina was thinner, but no significant degeneration, necrosis, karyopyknosis or lysis were found under the ultrastructural microscopy. CONCLUSION: Chitosan intravitreous tamponade has no significant effect on the histology of the eye, doesn't cause intraocular pressure to fluctuate, and slightly increases inflammatory factors (IL-6, IL-8, NO) in comparison to the normal levels, but with no significant difference from the effects caused by sodium hyaluronate, which indicated chitosan might not lead to a clinically significant inflammatory response. It suggests that chitosan could be used as intravitreous tamponade material.

[Preparation and characterization of novel degradable artificial lacrimal canaliculus].

OBJECTIVE: To develop a novel biodegradable collagen-chitosan-[poly(vinyl alcohol), PVA] composite artificial lacrimal canaliculus for treating tear overflowing (epiphora) caused by canalicular obstruction. METHODS: Homo-generously mixing solution composed of collagen, chitosan and PVA with different ratios was prepared. After several cycles of freezing/thawing process, the mixing solution was transferred into elastic hydrogel. Then the hydrogel was rinsed, punctured, dehydrated and trimmed, and three groups (T1, T2 and T3) of novel artificial lacrimal canaliculus were obtained. The appearance and diameter of all samples were observed under optical microscopy. The cross-section before and after drying as well as phase distribution of sample T2 was observed by SEM. The water absorption ratio and expanding ratio in PBS solution were calculated from three swelling behavior curves. The degradability of groups T1, T2 and T3 were preliminary analyzed by degradation experiment in vitro. RESULTS: The micro-tubes with 0.5-0.7 mm in inner diameter, 0.9-1.5 mm in outer diameter and more than 20 mm in length were fabricated successfully through physical crosslinking without addition of toxic cross-linker. SEM result showed that the sample had uniform phase distribution and smooth surface at dried state as well as interpenetrate network structure at hydrogel state. It was seen from the swelling behavior curves that groups T1, T2 and T3 swelled rapidly within 10-30 minutes, and formed elastic composite hydrogel pipes. In addition, the expanding ratio of inner and outer diameter of the tube was 20%-30% and 100%-120% with swelling, respectively. The equilibrium water content of the hydrogel pipes increased with increase of collagen composition. Three groups of samples were immersed in PBS solution contained 2 mg/mL lysozyme at 37 degrees C for 1 month, their nozzle cracked, their wall became thin and more transparent. And also, there was small floc deposited on the tube surface. The samples were degraded into mash after they were soaked in PBS solution at 70 degrees C for 2 days. CONCLUSION: The novel artificial lacrimal canaliculus with good mechanical property and high water absorption is in favor of operation, tear passing and anti-conglutination. It will be a potential candidate for treating the lacrimal passage occlusion.

[A prospective study on wound-healing hydrogel in treating chronic venous ulcer of lower extremities].

OBJECTIVE: To study the outcome of wound-healing hydrogel in treating chronic venous ulcer of lower extremities so as to find a new therapy. METHODS: From April 2007 to September 2007, 60 patients with chronic venous ulcer of lower extremities were randomly assigned to wound-healing hydrogel group (group A, 30 cases) and control group (normal saline, group B, 30 cases). In group A, there were 24 males and 6 females, aging (57.3 +/- 6.8) years; the disease course was (2.9 +/- 0.7) years; and the ulcer area was (3.4 +/- 0.6) cm2. In group B, there were 20 males and 10 females, aging (60.1 +/- 7.4) years; the disease course was (3.3 +/- 0.9) years; and the ulcer area was (3.1 +/- 0.4) cm2. There were no differences in age, area of ulcer and course of disease between two groups (P > 0.05). The area of ulcer was measured every week after the treatment, and the effect of treatment was evaluated after 15 days. RESULTS: The ulcer area of 7 days and 14 days after treatment was (2.6 +/- 0.7) and (1.1 +/- 0.2) cm2 in group A, and (2.8 +/- 0.6) and (2.3 +/- 0.7) cm2 in group B, respectively; showing no statistically significant differences 7 days after treatment (P > 0.05), and showing statistically significant difference 14 days after treatment between two groups (P < 0.05). The average healing time was (12.0 +/- 1.7) days in group A, and (31.0 +/- 2.9) days in group B, respectively, showing statistically significant difference (P < 0.01). The results were excellent, good, fair and poor in 16, 9, 4 and 1 of group A, and were in 3, 9, 14 and 4 of group B, respectively; showing statistically significant difference (P < 0.01). CONCLUSION: Wound-healing hydrogel is effective in treating chronic venous ulcer of lower extremities.

[Study on treating residual cavity of body surface after abscess drainage by sodium hyaluronate hydrogel].

OBJECTIVE: To study the effect of sodium hyaluronate hydrogel in treating residual cavity on body surface after abscess drainage so as to provide new method to speed up the healing of residual cavity after body surface abscess drainage and reduce the frequency of dressing change and clinic nursing workload. METHODS: From June 2007 to March 2008, 60 outpatients with body surface abscess drainage were randomly divided into hydrogel group (group A, 30 cases) and the control group (group B, 30 cases). In group A, there were 16 males and 14 females aged (49.5 +/- 6.1) years, the disease course was (3.8 +/- 0.6) days, and the volume of residual cavity was (4.19 +/- 1.31) mL. In group B, there were 18 males and 12 females aged (50.2 +/- 7.6) years, the disease course was (4.3 +/- 0.5) days, and the volume of residual cavity was (4.04 +/- 1.22) mL. There was no significant difference between two groups in gender, age, disease course and volume of residual cavity (P > 0.05). Residual cavity was smeared with 1 mL/cm2 sodium hyaluronate hydrogel in group A and drained by saline gauze in group B, the dressing was changed every two to three days. Residual cavity volume was recorded every four days, and the residual cavity volume, the frequency of out-patient dressing and the healing time residual of cavity were compared. RESULTS: The volume of residual cavity was (3.11 +/- 1.12), (1.75 +/- 0.95) and (0.55 +/- 0.56) mL in group A, and was (3.39 +/- 1.12), (2.64 +/- 0.99) and (1.81 +/- 0.81) mL in group B at 4, 8 and 12 days after treatment respectively, showing no significant differences at 4 days (P > 0. 05), but significant difference at 8 and 12 days (P < 0.01). Residual cavity healing time was (12.70 +/- 2.78) days in group A and (20.27 +/- 3.89) days in group B, and the frequency of dressing change was 5.53 +/- 1.33 in group A and 9.13 +/- 1.81 in group B, indicating significant differences between two groups (P < 0.01). CONCLUSION: Sodium hyaluronate hydrogel can promote residual cavity healing, reduce the frequency of dressing change of out-patient and decrease the clinic nursing care workload.

[The industrialization of regenerative medicine--a potential market of $ 500 billion].

OBJECTIVE: To investigate the latest development of tissue engineered regenerative medicine in industrialization, with the intention to direct work in practical area. METHODS: A complete insight of regenerative medicine in industrialization was obtained through referring to update publications, visiting related websites, as well as learning from practical experience. RESULTS: The aerial view of the future of regenerative medicine was got based on knowledge of four different tissue engineering projects. CONCLUSION: All present efforts should be devoted to regenerative medicine area meeting the industrialized trends.

[Preparation and evaluation of chitosan/alginate microsphere as a novel biodegradable haemostatic powder].

OBJECTIVE: To explore a way to make a new kind of chitosan-based microsphere (MS), which can be used as a novel biodegradable haemostatic powder, and to confirm its haemostatic efficiency. METHODS: Chitosan (CTS), a haemostatic polysaccharide, was selected as a main material for the haemostatic powder; alginate (ALG), another haemostatic polysaccharide that has been found to be effective in promoting haemostasis in surgical procedures, was selected to be the costar. The emulsification and the cross-link were chosen as a preparation process based on the interaction between the polysaccharides. The diameter of the prepared MS was determined by SPOS, and the surface of MS was observed under SEM. The swelling characteristics of MS in the simulative wound efflusion were investigated. In a splenic bleeding model in 6 rabbits, MS and Yunnanbaiyao were randomly used as a haemostatic agent, and the corresponding bleeding time was recorded. RESULTS: The MS prepared in the above-mentioned process was well proportioned and was similarly shaped. It became a kind of white powder after dehydration, and had a coralloid surface under SEM. The diameter of the MS was 4.05+/-2.55 microm, which was determined by SPOS. The swelling ratio of the MS was 280.139% within 5 min. The bleeding time was significantly decreased in the MS treated group (2.83+/-0.17 min) when compared with that in the control group (5.33+/-0.49 min)(P<0.01). CONCLUSION: The CTS/ALG-MS, which is made from haemostatic biomaterials (CTS, ALG) by emulsification and the cross-link processes, can be provided with favorable haemostatic efficiency. It can be used as a novel haemostatic powder. However, its biodegrading rate and mode still remain to be further studied.

[Preparation of carboxymethylchitin and studies on its properties].

OBJECTIVE: To prepare carboxymethylchitin and study its properties. METHODS: Chitin was prepared from fresh shrimp shells and then carboxymethylchitin was prepared by the methods of alkalization and etherification as well as by the purification technique. The deacetylation degree of carboxymethylchitin was determined by the double-jump potentiometric titration method; the substitution degree was determined by the element analysis method; the carboxymethyl substitution position was analyzed by the Fourier transform infrared spectroscopy apparatus and the nuclear magnetic resonance spectroscopy apparatus; the relative molecular weight and its polydispersity were determined by the gel permeation chromatography with the multiple angle laser light scattering detection; the biological properties were tested according to the GB/T 16886 biological evaluation on medical devices. RESULTS: Carboxymethylchitin could be prepared by alkalization and etherification from chitin which was prepared from fresh shrimp shells by decalcification and deproteinization. The deacetylation degree of carboxymethylchitin was 13.76% according to the double-jump potentiometric titration; the degrees of deacetylation and substitution were 14.53% and 1.2390 respectively according to the element analysis. The IR spectrum showed that the substitutive position was N, O-substitution, and the 13C-NMR spectrum showed that substitutive position of carboxymethylchitin was mostly primary substitution of 6-OH, and according to the substitutive proportion, the substitutive turns were in the following decreasing order: 6-OH, NH2, and 3-OH. The weight-averaged and the number-averaged molecular weights and polydispersity were 6. 25 x 10(5), 5.60 x 10(5) and 1.22, respectively. The results from the biological property test showed that carboxymethylchitin was a biomaterial that was sterile, pyrogen-free, acute toxicity-free, cytotoxicity-free, intracutaneous irritation-free, skin sensitization-free and biomaterial genotoxicity-free, with no side or adverse effects on the related tissues after implantation into the human body. CONCLUSION: Carboxymethylchitin prepared from chitin by alkalization and etherification is a macromolecule biomaterial that has a low degree of deacetylation, a high degree of substitution, and a good biocompatibility.

[Biomaterials used for reparative and reconstructive surgery].

OBJECTIVE: To investigate the currently-used biomaterials in reparative and reconstructive surgery and to clarify the relationship between the development of biomaterials and the progress of reparative and reconstructive surgery. METHODS: Based on the author's many years' scientific researches and combined with the literature available at home and abroad, the biomaterials used in the clinical practice, and their kinds and application fields were summarized. RESULTS: Based on the sufficient knowledge of the component structure of biomaterials and the patient's pathological status, the matching biomaterials could be designed and developed. According to the analysis on some common defects occurring in the skin, bone, cartilage, vocal cord, nerve, and drum membrane, the methods of repairing the defects with biomaterials that we had developed, such as collagen, chitosan, and hyaluronate, achieved good results. CONCLUSION: The rapid development of biomaterials can greatly promote progress of reparative and reconstructive surgery and there exists a dependence relationship between the two. The related histological responses and the importance of biological estimation after implantation of biomaterials should be emphasized.

[Clinical application of collagen].

OBJECTIVE: To review and evaluate the extensive and further research and the application of the collagen-based biomaterials in the field of clinical medicine. METHODS: The clinical research and application of collagen-based biomaterials were comprehensively reviewed and evaluated on the basis of the up-to-date publications and our practical experiences in their studies and manufacturing. RESULTS: The following five aspects concerned with the collagen-based biomaterials were evaluated: biological property, quality control, formulation of substrate and clinical application, immunogenicity and clinical side effect, and potential of the market development. CONCLUSION: Collagen-based biomaterials have a great potential and market space in their clinical application.

[Research of cross-linking reagent for producing hyaluronic acid derivative].

OBJECTIVE: To review the recent advances of cross-linking reagent for producing hyaluronic acid (HA) derivative so as to provide more advice for the development of HA reagent. METHODS: Recent original articles related to the species, characteristic, cross-linking methodology and mechanism of the cross-linking reagent to producing HA derivative were summarized and systematically analyzed. RESULTS: The derivatives after special kinds of reagents modification would remain their own good biocompatibility and change their original rheololgical characterization and obtain relative long organism residence time. CONCLUSION: Development of hyaluronic derivatives may widen their medical application.