Bio-Medical Materials and Engineering - Volume 30, issue 1

Authors: Liu, Chenghu | Lin, Zhenhua | Qiao, Chunxia | Zhao, Zenglin | Wang, Changbin | Sun, Xiaoxia | Shi, Yanping

Article Type: Research Article

Abstract: For medical devices directly or indirectly contacted with blood, hemocompatibility assay is of great importance during the biological evaluation. In ISO 10993-4:2017 - Biological evaluation of medical devices part 4, a selection of tests for interactions with blood is given with the rationale for selection of tests based on their intended use specified, however, the specific testing protocols may vary significantly when performing the hemocompatibility assays. In recent years, medical catheters have been widely used in clinical practice. Moreover, a lot of surface modified catheters emerged in the market to enhance their performance of hemocompatibility especially for hydrophilic coating catheters. …Unfortunately, to date, the hemocompatibility of hydrophilic coating still remains controversial due to the inherent complexity of the hemocompatibility test itself and lack of validated test methods. In this study, through determining the hemocompatibility performance for a micro-catheter with a typical hydrophilic pyrrolidone coating regarding haemolysis test, partial thromboplastin time (PTT), prothrombin time (PT) and thrombogenicity test in dogs, we have established a series of tentative hemocompatibility protocols for these tests. Hopefully, our study could not only provide some useful information for hemocompatibility evaluation on medical catheters with a hydrophilic coating but could also contribute to the development of neo-type hemocompatible medical devices for better clinical practice. Show more

Keywords: Hemocompatibility assay, micro-catheter, coating biomaterials

DOI: 10.3233/BME-181028

Citation: Bio-Medical Materials and Engineering, vol. 30, no. 1, pp. 1-9, 2019

Authors: Qian, Jiajia | Cheng, Weiye | Zhang, Caiyun | Hong, Lufeng | Chen, Weidong | Li, Guoxi

Article Type: Research Article

Abstract: In order to enhance lipophilicity and oral bioavailability of paeoniflorin (PF), this study developed paeoniflorin-phospholipid complex (PF-PLC) by solvent-evaporation method. The optimum preparation technology of PF-PLC was screened by the combination of single factor and orthogonal experiment. The physicochemical properties of PF-PLC were evaluated via differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and oil-water partition coefficient study (lgP ). The result of FTIR spectra indicated that there was some strong hydrogen bond interaction and good compatibility between the phospholipid molecule and PF in the complex. DSC and XRD structure analysis showed that PF was in …form of amorphous structure in PF-PLC, and lgP of PF-PLC was enhanced, suggesting that the lipophilicity of PF-PLC was higher than that of PF. In vitro release of PF-PLC showed slower release than PF solution with its cumulative release rate of 93.81% at 24 h compared to 93.43% of PF at 1.5 h. In pharmacokinetic experiments, the AUC and Cmax of the PF-PLC were 1.97-fold and 2.5-fold higher than PF solution. These results suggested that PF-PLC could enhance lipophilicity and oral bioavailability of PF and provide a promising delivery system for the application of PF. Show more

Keywords: Paeoniflorin, phospholipid complex, oral bioavailability, lipophilicity

DOI: 10.3233/BME-181029

Citation: Bio-Medical Materials and Engineering, vol. 30, no. 1, pp. 11-22, 2019

Authors: Ma, Yanchao | Li, Yanhong | Hao, Junlong | Ma, Bin | Di, Tianning | Dong, Haitao

Article Type: Research Article

Abstract: BACKGROUND: Calcium polyphosphate (CPP) is a commonly used biomaterial in bone tissue engineering, but CPP is insufficient in osteoinduction. This study aimed to fabricate lithium doped CPP (LiCPP) scaffolds and assess their characterization, degradation, biocompatibility and osteogenesis behavior for bone tissue engineering. METHODS: The novel scaffold was characterized by XRD, FTIR and SEM. The porosity, cell mediated degradation behavior and mechanical properties were also investigated. Meanwhile, cell proliferation activity and adhesion in vitro was exploited. Finally, osteogenesis the LiCPP scaffolds in vitro and in vivo was researched. RESULTS: The outcomes revealed that low-content Li doping had …no significant influence on the structure of CPP. The results of cells mediated degradation experiments from the weight loss and the release of ions indicated that Li doped CPP improved biological degradation. The compressive strength of CPP with 66% porosity was improved to 7 MPa. Cells proliferation experiment and adhesion experiment demonstrated 2.0%LiCPP scaffold was most beneficial to cell growth and attachment. Furthermore, Li doped CPP up-regulated Wnt signal pathway when co-cultured with MG63 and increased osteogenic marker ALP expression and calcium phosphate deposition in vitro. At the same time, new bone formation in vivo was also enhanced by using LiCPP scaffolds and the 2.0%LiCPP scaffolds obtained best osteogenesis outcomes. CONCLUSION: The results obtained in our study suggest that 2.0%LiCPP scaffold could benefit from improving the osteogenesis behavior and is a promising biomaterial for bone repairing applications. Show more

Keywords: Calcium polyphosphate, lithium, osteogenesis, bone tissue engineering, degradation

DOI: 10.3233/BME-181030

Citation: Bio-Medical Materials and Engineering, vol. 30, no. 1, pp. 23-36, 2019

Authors: Herrmann, Florian Ernst Martin | Lehner, Anja | Koenig, Fabian | Hollweck, Trixi | Fano, Cornelia | Dauner, Martin | Eissner, Guenther | Hagl, Christian | Akra, Bassil

Article Type: Research Article

Abstract: BACKGROUND/OBJECTIVE: Ischemic heart disease is a major cause of mortality worldwide. Myocardial tissue engineering aims to create transplantable units of myocardium for the treatment of myocardial necrosis caused by ischemic heart disease – bioreactors are used to condition these bioartificial tissues before application. METHODS: Our group developed a multimodal bioreactor consisting of a linear drive motor for pulsatile flow generation (500 ml/min) and an external pacemaker for electrical stimulation (10 mA, 3 V at 60 Hz) using LinMot-Talk Software to synchronize these modes of stimulation. Polyurethane scaffolds were seeded with 0.750 × 106 mesenchymal stem cells from umbilical cord tissue per …cm2 and stimulated in our system for 72 h, then evaluated. RESULTS: After conditioning histology showed that the patches consisted of a cell multilayer surviving stimulation without major damage by the multimodal stimulation, scanning electron microscopy showed a confluent cell layer with no cell-cell interspaces visible. No cell viability issues could be identified via Syto9-Propidium Iodide staining. CONCLUSIONS: This bioreactor allows mechanical stimulation via pulsatile flow and electrical stimulation through a pacemaker. Our stem cell-polyurethane constructs displayed survival after conditioning. This system shows feasibility in preliminary tests. Show more

Keywords: Bioreactors, tissue engineering, heart disease, myocardium, stem cells

DOI: 10.3233/BME-181031

Citation: Bio-Medical Materials and Engineering, vol. 30, no. 1, pp. 37-48, 2019

Authors: Takahashi, Tatsunori | Itoh, Soichiro | Kida, Masakazu

Article Type: Research Article

Abstract: OBJECTIVE: We conducted ultrasonography (US) examination for asymptomatic elbow injuries in judo athletes to confirm availability of US screening for elbow. MATERIALS AND METHODS: One hundred and thirty-two black belts in judo (85 males and 47 females; mean age, 20.0 ± 1.6 years) participated in this screening. Forty-eight participants had a history of elbow injury (elbow-injury group), and 84 did not (no-elbow-injury group). All participants completed a survey in the form of a questionnaire. Subsequently, US scanning of both elbows was performed. RESULTS: The maximal thickness of the medial collateral ligament of both elbows was significantly …larger in the elbow-injury group than in the no-elbow-injury group. The width of the joint space was significantly larger in the right radiohumeral joint in the elbow-injury group than in the no-elbow-injury group. Combination injuries involving ligament and bone and those involving both the medial and lateral collateral ligaments were most commonly seen in both elbows in the elbow-injury group; however, these combined lesions of both elbows were also found in the no-elbow-injury group. CONCLUSIONS: Because US screening can reveal abnormalities of the asymptomatic elbow, US is recommended as a complementary imaging modality that is useful for evaluation of elbow injuries in athletes. Show more

Keywords: Elbow injury, ultrasound screening, collateral ligament, asymptomatic elbow injuries, judo athlete

DOI: 10.3233/BME-181032

Citation: Bio-Medical Materials and Engineering, vol. 30, no. 1, pp. 49-59, 2019

Authors: Mallis, Panagiotis | Michalopoulos, Efstathios | Pantsios, Paschalis | Kozaniti, Foteini | Deligianni, Despoina | Papapanagiotou, Aggeliki | Stavropoulos Giokas, Catherine

Article Type: Research Article

Abstract: BACKGROUND: The primary therapeutic strategy in cardiovascular disease is the coronary artery bypass surgery, which in- volves the use of small diameter vascular grafts (<6 mm). Human umbilical arteries could be used as a source for the development of these grafts. OBJECTIVE: The aim of this study was the decellularization of human umbilical arteries and the evaluation of their re- cellularization potential. METHODS: Decellularization of human umbilical arteries was performed with a detergent based protocol. Histological analysis was performed in order to determine the effect of decellularization. Then, recellularization was performed by using two …different approaches. The first approach was the dynamic seeding of human umbilical arteries with Mesenchymal Stromal Cells and the second approach involved the recellularization by using a bioreactor system. RESULTS: Histological analysis showed the successful removal of cellular and nuclear materials from the umbilical arteries. In addition, successful recellularization of the vessels was observed with both approaches. CONCLUSION: The results of this study indicated that human umbilical arteries could serve as an alternative material for the proper development of small diameter vascular grafts. Show more

Keywords: Human umbilical arteries, decellularization, bioreactor, tissue engineering, small diameter vascular grafts, extracellular matrix, collagen, SDS, recellularization, cardiovascular disease

DOI: 10.3233/BME-181033

Citation: Bio-Medical Materials and Engineering, vol. 30, no. 1, pp. 61-71, 2019

Authors: Peerapattana, Jomjai | Hattori, Yusuke | Otsuka, Makoto

Article Type: Research Article

Abstract: BACKGROUND: In order to manufacture pharmaceutical products, real-time monitoring in the manufacturing process is necessary, but large equipment cost is required to achieve it. OBJECTIVE: The aim of this research is to use ultra-violet-visible spectroscopy along with chemometrics procedure to simultaneously carry out quantitative analysis of indomethacin (IMC) and benzoic acid (BA) in the gel during pharmaceutical manufacturing process. METHODS: The gel preparations contained 0.1–1.5% IMC, 0.015–0.225% BA, 2% carbopol® 941 and 95% ethanol solution. The calibration models were constructed using the partial least square regression (PLS). RESULTS: The relationships of the measured …and predicted concentrations for both IMC and BA had linear plots. The developed PLS calibration models were used to monitor the IMC and BA concentrations during mixing of the gels by the planetary centrifugal and conventional mixers, respectively. IMC and BA were gradually dispersed, dissolved and completely homogeneous within 30 min by the centrifugal mixer. In contrast, IMC and BA were slowly dispersed, dissolved and completely homogeneous at more than 60 min by the conventional mixer. CONCLUSIONS: The ultra-violet-visible spectrophotometric method couples with multivariate chemometric techniques for quantitative data analysis were successfully applied for the simultaneous determination of major component IMC and trace component BA in the gel. Show more

Keywords: Ultra-violet-visible spectroscopy, indomethacin, benzoic acid, process monitoring, partial least square regression, process analysis technology

DOI: 10.3233/BME-181034

Citation: Bio-Medical Materials and Engineering, vol. 30, no. 1, pp. 73-84, 2019

Authors: Kalinichenko, Sergei G. | Matveeva, Natalya Yu | Kostiv, Roman Ye | Edranov, Sergey S.

Article Type: Research Article

Abstract: BACKGROUND: Biodegradable implant coatings promote proliferation and expression of BMP-2, VEGF, and TGF-β2 genes and enhance BMP-2, VEGF, and TGF-β2 regulatory effects at different stages of reparative osteogenesis. OBJECTIVE: To study the topography and ratio of PCNA-, VEGF-, BMP-2-, and TGF-β2-immunoreactive cells in rat femoral bone after closed fracture and implantation of titanium implants with biodegradable calcium phosphate and hydroxyapatite coatings. METHODS: Standard titanium implant screws and similar implants with bioactive coatings were used. A total of 18 rats were randomly divided into three groups, two experimental and a control one. The rats in the first …experimental group were implanted with implants without specific coating, while those in the second group, with implants with specific coatings. The control rats were subjected to the same fracture as the experimental ones without subsequent implantation. On days 7, 14, and 30 of experiment, the rats were sampled for histological examination. Histological sections were prepared and processed for PCNA, BMP-2, VEGF, and TGF-β2 immunoreactivity. RESULTS: In the regeneration zone, PCNA-immunoreactive cells substantially outnumbered other immunoreactive cell types. During the first two weeks after fracture, in the immediate vicinity of implant surface, the rate of VEGF production increased in osteoblast subpopulations and level of TGF-32 immunoreactivity decreased in chondroblasts. The level of TGF-32 was maximum on day 30 of experiment. BMP-2-immunoreactive osteocytes were found in the zone of external general plates. They accumulated at implants with calcium phosphate coating. Their number gradually increased by day 30 of experiment. CONCLUSIONS: The present data suggest that biodegradable implant coatings promote proliferation and expression of BMP-2, VEGF, and TGF-β2 genes and enhance BMP-2, VEGF, and TGF-β2 regulatory effects at different stages of reparative osteogenesis. Show more

Keywords: Biodegradable nanostructure materials, morphogenetic factors, bone tissue remodelling, implant coatings, osseointegration

DOI: 10.3233/BME-181035

Citation: Bio-Medical Materials and Engineering, vol. 30, no. 1, pp. 85-95, 2019

Authors: Limón-Martínez, R.J. | Olivas-Armendáriz, I. | Sosa-Rodarte, E. | Rodríguez-Rodríguez, C.I. | Hernández-Paz, J.F. | Acosta-Torres, L.S. | García-Contreras, R. | Santos-Rodríguez, E. | Martel-Estrada, S.A.

Article Type: Research Article

Abstract: BACKGROUND: The development of biomaterial scaffolds and implementation of tissue engineering techniques are necessary. Therefore, Polycaprolactone/Sodium Hyaluronate/Multiwalled Carbon Nanotubes/Extract of Mimosa tenuiflora composites have been produced by a thermally-induced phase separation method. OBJECTIVE: The objective of this research was to evaluate the in vitro bioactivity and in vitro biocompatibility of the composites. METHODS: The in vitro bioactivity of the composites was assessed by soaking them in simulated body fluid for 7, 14, 21, and 28 days. The structure and composition of the composites were analyzed using scanning electron microscopy coupled with …energy dispersive spectroscopy and Fourier transform infrared spectroscopy. Also, the in vitro biocompatibility of the composites was evaluated by means of alkaline phosphatase activity of the osteoblasts and by measuring the metabolic activity of the cells using MTT assay. RESULTS: The results show a porous and interconnected morphology with enhanced bioactivity. It was observed that the incorporation of Mimosa tenuiflora in the composites promotes increased viability of osteoblasts in the scaffolds. CONCLUSIONS: The results show the efficiency of bioactive and biocompatible composites and their potential as candidates for tissue engineering applications. Show more

Keywords: Bioactive materials, polycaprolactone, sodium Hyaluronate, MWCNT, Mimosa tenuiflora , SBF, MTT assay

DOI: 10.3233/BME-181036

Citation: Bio-Medical Materials and Engineering, vol. 30, no. 1, pp. 97-109, 2019

Authors: Bi, Xiangdong | Maturavongsadit, Panita | Tan, Yu | Watts, Morgan | Bi, Evelyn | Kegley, Zachary | Morton, Steve | Lu, Lin | Wang, Qian | Liang, Aiye

Article Type: Research Article

Abstract: BACKGROUND: Biocompatible hydrogel systems with tunable mechanical properties have been reported to influence the behavior and differentiation of mesenchymal stem cells (MSCs). OBJECTIVE: To develop a functionalized hydrogel system with well-defined chemical structures and tunable mechanical property for regulation of stem cell differentiation. METHODS: An in situ- forming hydrogel system is developed by crosslinking vinyl sulfone functionalized polyamidoamine (PAMAM) dendrimer and multi-armed thiolated polyethylene glycol (PEG) through a thiol-ene Michael addition in aqueous conditions. The viability and differentiation of MSCs in hydrogels of different stiffness are conducted for 21 days under corresponding induction media. …RESULTS: MSCs are viable in synthesized hydrogels after 48 hours of culture. By varying the concentrations of PAMAM dendrimer and PEG, hydrogels of different gelation time and stiffness are achieved. The MSC differentiation indicates that more osteogenic differentiation is observed in hard gel (5,663 Pa) and more adipogenic differentiation is observed in soft gel (77 Pa) in addition to the differentiation caused by each individual induction media during the process of culture. CONCLUSIONS: A biocompatible in situ -forming hydrogel system is successfully synthesized. This hydrogel system has shown influences on differentiation of MSCs and may potentially be important in developing therapeutic strategies in medical applications. Show more

Keywords: Hydrogel, PAMAM dendrimer, mesenchymal stem cells, osteogenic differentiation, adipogenic differentiation

DOI: 10.3233/BME-181037

Citation: Bio-Medical Materials and Engineering, vol. 30, no. 1, pp. 111-123, 2019