Bio-Medical Materials and Engineering - Volume 33, issue 5

Authors: Wadugodapitiya, Surangika | Sakamoto, Makoto | Tanaka, Masaei | Sakagami, Yuta | Morise, Yusuke | Kobayashi, Koichi

Article Type: Research Article

Abstract: BACKGROUND: Knowledge of the biomechanics of the normal collateral ligaments is important to secure optimal stability of the knee following injury. Various in vitro methods have been described in evaluating the biomechanics of these ligaments. However, a method of direct evaluation has not been reported. OBJECTIVE: To determine the stiffness characteristics of the collateral ligaments of the knee using strain ultrasound elastography. METHODS: Strain ultrasound elastography was performed on different components of the collateral ligaments in various angles of knee flexion in 18 healthy males (36 ligaments). We measured relative stiffness of the ligaments using strain …ratio (SR = target tissue strain/reference strain). A lower strain ratio indicates higher relative stiffness. RESULTS: There was moderate to excellent intra- and inter-rater agreement for strain ratio measurements in all ligament portions. Strain ratios were lowest at 0° in all three ligaments, indicating high relative stiffness. In the superficial and deep medial collateral ligaments, the strain ratio increased with increasing knee flexion, whereas in the lateral collateral ligament, stiffness showed a tendency to fluctuate. CONCLUSION: Strain ultrasound elastography is a reliable tool for monitoring relative stiffness of the collateral ligaments of the knee and is easily applied to the routine clinical setting. Show more

Keywords: Knee collateral ligament, strain ultrasound elastography, strain ratio, relative stiffness, flexion angle

DOI: 10.3233/BME-211282

Citation: Bio-Medical Materials and Engineering, vol. 33, no. 5, pp. 337-349, 2022

Authors: Wang, Yuying | He, Rui | Yang, Anqi | Guo, Rui | Liu, Jie | Liang, Guoqing | Sheng, Donglai | Zhong, Liangjun

Article Type: Research Article

Abstract: BACKGROUND: The effectiveness and availability of conservative therapies for osteonecrosis of the femoral head (ONFH) are limited. Transplantation of bone marrow mesenchymal stem cells (BMSCs) combined with Bio-Oss, which is a good bone scaffold biomaterial for cell proliferation and differentiation, is a new potential therapy. Of note, the expression of miRNAs was significantly modified in cells cultured with Bio-Oss, and MiR-214 was correlated positively with osteonecrosis. Furthermore, miR-214 was upregulated in cells exposed to Bio-Oss. OBJECTIVE: To investigate whether targeting miR-214 further improves the transplantation effect. METHODS: We treated BMSCs with agomiR-214 (a miR-214 agonist), antagomiR-214 …(a miR-214 inhibitor), or vehicle, followed by their transplantation into ONFH model rats. RESULTS: Histological and histomorphometric data showed that bone formation was significantly increased in the experimental groups (Bio-Oss and BMSCs treated with antagomiR-214) compared with other groups. CONCLUSIONS: miR-214 participates in the inhibition of osteoblastic bone formation, and the inhibition of miR-214 to bone formation during transplantation therapy with Bio-Oss combined with BMSCs for ONFH. Show more

Keywords: Bio-Oss, BMSCs, miR-214, bone regeneration, transplantation therapy

DOI: 10.3233/BME-211296

Citation: Bio-Medical Materials and Engineering, vol. 33, no. 5, pp. 351-364, 2022

Authors: Liu, Juan | He, Hongyan | Tang, Lu | Peng, Yu | Mu, Junyu | Lan, Liang | Chen, Cheng | Dong, Zhihong | Cheng, Lijia

Article Type: Research Article

Abstract: BACKGROUD: Calcium phosphate biomaterials have excellent bone inductivity, and exercise can promote the bone formation of biomaterials in animals, but it is not clear which exercise mode is better. OBJECTIVE: To explore the effect of different exercise modes on osteoinduction by calcium phosphate-based biomaterials which were implanted in mice. METHOD: The collagen-thermosensitive hydrogel-calcium phosphate (CTC) composite was prepared and transplanted in the thigh muscle of mice, then all mice were divided randomly into four groups (n = 10): the uphill running group, the downhill running group, the swimming group and the control group (conventional breeding). Ten …weeks later, the samples were harvested, fixed, decalcified, embedded in paraffin and stained with hematoxylin and eosin (H&E), and then the osteoinduction phenomenon was observed and compared through digital slice scanning system. The area percentage of new bone-related tissues and the number of osteocytes and chondrocytes were counted and calculated. Lastly, the immunohistochemistry of type I collagen (ColI) and osteopontin (OPN) was performed to identify the new bone tissues. RESULTS: The area percentage of new bone-related tissues and the number of osteocytes and chondrocytes were positively correlated; ordering from most to least of each group were as followings: the uphill running group > the swimming group > the downhill running group > the control group. The immunostaining of ColI and OPN results showed that both of the two proteins were identified in the new bone tissues, indicating that the CTC composite could induce ectopic bone formation in mice, especially training for uphill running and swimming. CONCLUSION: Our results show that uphill running or swimming is a form of exercise that is beneficial to osteogenesis. According to this, we propose treatment with artificial bone transplantation to patients who suffer from bone defects. Patients should do moderate exercise, such as running uphill on the treadmill or swimming. Show more

Keywords: Osteoinduction, uphill running, swimming, biocomposite, artificial bone

DOI: 10.3233/BME-211341

Citation: Bio-Medical Materials and Engineering, vol. 33, no. 5, pp. 365-375, 2022

Authors: Marx, Daniella | Papini, Marcello | Towler, Mark

Article Type: Research Article

Abstract: BACKGROUND: Glass polyalkenoate cements (GPCs) are bio-adhesives which consist of ionomeric glass particles embedded in a poly-salt matrix. These materials have been used in dentistry and orthodontics extensively but are presently being optimized as bone putties for orthopedic applications. OBJECTIVE: This study utilized a patented ionomeric glass (mole fraction: SiO2 :0.48, ZnO:0.36, CaO:0.12, SrO:0.04) to formulate two GPCs: GPC A (<45 μm particle size glass) and GPC B (45 μm–63 μm). These formulations were previously assessed for their effect on osteoblast viability and osteogenic function. However, the immunomodulatory effects of GPC A and B have not previously been investigated. …METHOD: Non-toxic concentrations of (a) GPC dissolution products and (b) fragmented GPC particles were tested for their ability to affect the secretion of cytokines (TNF-α, IL-1β, IL-6 and IL-10) by rat peripheral blood mononuclear cells (PBMCs), in the presence or absence of the stimulant liposaccharide (LPS). Additionally, the ionic concentrations of Sr, Zn, Ca, and Si were measured in GPC ionic extracts, and the size, shape and concentration of fragmented GPC particles in deionized water were characterized using an optical microscope-based particle analyzer. RESULTS: The results showed that GPC A ionic products reduced the concentration of TNF-α secreted by stimulated cells compared with cells stimulated in the absence of GPC products. Interestingly, the particles released from GPC A significantly increased the secretion of both TNF-α and IL-6 from unstimulated cells, compared to control cells. CONCLUSION: Neither GPC B ionic products nor released particles were found to be biologically active with respect to PBMC cytokine secretion. Show more

Keywords: Glass polyalkenoate cements, inflammation, in vitro, zinc, strontium

DOI: 10.3233/BME-211346

Citation: Bio-Medical Materials and Engineering, vol. 33, no. 5, pp. 377-391, 2022

Authors: Nagayama, Kazuaki | Hanzawa, Tatsuya

Article Type: Research Article

Abstract: BACKGROUND: Directional cell migration due to mechanosensing for in vivo microenvironment, such as microgrooved surfaces, is an essential process in tissue growth and repair in both normal and pathological states. Cell migration responses on the microgrooved surfaces might be reflected by the cell type difference, which is deeply involved in cellular physiological functions. Although the responses are implicated in focal adhesions (FAs) of cells, limited information is available about cell migration behavior on the microgrooved surfaces whose dimensions are comparable with the size of FAs. OBJECTIVE: In the present study, we investigated the cell orientation and migration behavior …of normal vascular smooth muscle cells (VSMCs) and cervical cancer HeLa cells on the microgrooved surface. METHOD: The cells were cultured on the PDMS substrate comprising shallow grooves with 2-µm width and approximately 150-nm depth, which indicates the same order of magnitude as that of the horizontal and vertical size of FAs, respectively. The cell migration and intracellular structures were analyzed by live cell imaging and confocal fluorescence microscopy. The intracellular tension was also assessed using atomic force microscopy (AFM). RESULTS: VSMCs presenting well-aligned actin stress fibers with mature FAs revealed marked cell elongation and directional migration on the grooves; however, HeLa cells with nonoriented F-actin with smaller FAs did not. The internal force of the actin fibers was significantly higher in VSMCs than that in HeLa cells, and the increase or decrease in the cytoskeletal forces improved or diminished the sensing ability for shallow grooves, respectively. The results strongly indicated that directional cell migration should be modulated by cell type-specific cytoskeletal arrangements and intracellular traction forces. The differences in cell type-specific orientation and migration responses can be emphasized on the microgrooves as large as the horizontal and vertical size of FAs. CONCLUSION: The microgoove structure in the size range of the FA protein complex is a powerful tool to clarify subtle differences in the intracellular force-dependent substrate mechanosensing. Show more

Keywords: Cell biomechanics, mechanobiology, microgroove, cytoskeleton, focal adhesions

DOI: 10.3233/BME-211356

Citation: Bio-Medical Materials and Engineering, vol. 33, no. 5, pp. 393-406, 2022

Authors: Gao, Liping | Li, Xuexia | Tan, Rubin | Cui, Jie | Schmull, Sebastian

Article Type: Research Article

Abstract: BACKGROUND: Stem cells are used as an alternative treatment option for patients with congenital heart disease (CHD) due to their regenerative potential, but they are subject to low retention rate in the injured myocardium. Also, the diseased microenvironment in the injured myocardium may not provide healthy cues for optimal stem cell function. OBJECTIVE: In this study, we prepared a novel human-derived cardiac scaffold to improve the functional behaviors of stem cells. METHODS: Decellularized extracellular matrix (ECM) scaffolds were fabricated by removing cells of human-derived cardiac appendage tissues. Then, bone marrow c-kit+ progenitor cells from patients with …congenital heart disease were seeded on the cardiac ECM scaffolds. Cell adhesion, survival, proliferation and cardiac differentiation on human cardiac decellularized ECM scaffold were evaluated in vitro . Label-free mass spectrometry was applied to analyze cardiac ECM proteins regulating cell behaviors. RESULTS: It was shown that cardiac ECM scaffolds promoted stem cell adhesion and proliferation. Importantly, bone marrow c-kit+ progenitor cells cultured on cardiac ECM scaffold for 14 days differentiated into cardiomyocyte-like cells without supplement with any inducible factors, as confirmed by the increased protein level of Gata4 and upregulated gene levels of Gata4, Nkx2.5, and cTnT. Proteomic analysis showed the proteins in cardiac ECM functioned in multiple biological activities, including regulation of cell proliferation, regulation of cell differentiation, and cardiovascular system development. CONCLUSION: The human-derived cardiac scaffold constructed in this study may help repair the damaged myocardium and hold great potential for tissue engineering application in pediatric patients with CHD. Show more

Keywords: Extracellular matrix (ECM), c-kit, cardiac differentiation, tissue engineering, congenital heart disease

DOI: 10.3233/BME-211368

Citation: Bio-Medical Materials and Engineering, vol. 33, no. 5, pp. 407-421, 2022

Authors: Shembekar, Suraj N. | Zodpe, D.B. | Padole, P.M.

Article Type: Research Article

Abstract: BACKGROUND: Arteriovenous fistula (AVF) is the preferred route of vascular access in hemodialysis. The primary reason of fistula failure is intimal hyperplasia (IH), which leads to stenosis. Wall shear stress (WSS) and disturbed flow are the critical parameters in the formation of IH. OBJECTIVE: The primary goal of this study is to explore the influence of anastomosis angle on WSS and venous outflow rate, as well as to find the ideal angle of anastomosis for AVF to standardize surgical technique. METHODS: Three-dimensional idealized geometries of end-to-side type AVF for the five various angles of anastomosis are …considered in this study. The WSS, blood flow rate at the venous outlet for non-Newtonian, pulsatile blood flow are calculated using a numerical simulation technique. RESULTS: The WSS is higher at 75° compared to other angles and least at 45° for pulsating arterial inflows. The WSS is moderate at 30°, 60° and 90°. On the arterial bed and outer wall of the vein, immediately after the anastomosis, the recirculation zone is observed. At an angle of 45° and 90° anastomosis, the outflow rate is greater at distal venous end. CONCLUSIONS: If one believes that high wall shear stress causes IH within the AVF, the results suggest that the AVF should be formed at a 45° angle to avoid IH. However, if one believes that low wall shear stress causes IH within the AVF, the results suggest that AVF should be formed at either 30° or 75° to avoid IH. The findings spotlight the importance of anastomosis angle in determining AVF hemodynamics. Show more

Keywords: Arteriovenous fistula, anastomosis angle, hemodialysis, vascular access, wall shear stress

DOI: 10.3233/BME-211389

Citation: Bio-Medical Materials and Engineering, vol. 33, no. 5, pp. 423-436, 2022