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Most Cited Bioactive Materials Articles

The most cited articles published since 2015, extracted from Scopus.

Bioactive polymeric scaffolds for tissue engineering

Volume 1, Issue 2, December 2016, Pages 93-108
Scott Stratton | Scott Stratton | Namdev B. Shelke | Namdev B. Shelke | Kazunori Hoshino | Swetha Rudraiah | Sangamesh G. Kumbar | Sangamesh G. Kumbar | Sangamesh G. Kumbar

© 2016 The Authors. A variety of engineered scaffolds have been created for tissue engineering using polymers, ceramics and their composites. Biomimicry has been adopted for majority of the three-dimensional (3D) scaffold design both in terms of physicochemical properties, as well as bioactivity for superior tissue regeneration. Scaffolds fabricated via salt leaching, particle sintering, hydrogels and lithography have been successful in promoting cell growth in vitro and tissue regeneration in vivo. Scaffold systems derived from decellularization of whole organs or tissues has been popular due to their assured biocompatibility and bioactivity. Traditional scaffold fabrication techniques often failed to create intricate structures with greater resolution, not reproducible and involved multiple steps. The 3D printing technology overcome several limitations of the traditional techniques and made it easier to adopt several thermoplastics and hydrogels to create micro-nanostructured scaffolds and devices for tissue engineering and drug delivery. This review highlights scaffold fabrication methodologies with a focus on optimizing scaffold performance through the matrix pores, bioactivity and degradation rate to enable tissue regeneration. Review highlights few examples of bioactive scaffold mediated nerve, muscle, tendon/ligament and bone regeneration. Regardless of the efforts required for optimization, a shift in 3D scaffold uses from the laboratory into everyday life is expected in the near future as some of the methods discussed in this review become more streamlined.

Enhancing cell infiltration of electrospun fibrous scaffolds in tissue regeneration

Volume 1, Issue 1, September 2016, Pages 56-64
Jinglei Wu | Jinglei Wu | Yi Hong | Yi Hong

© 2016 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. Electrospinning is one of the most effective approaches to fabricate tissue-engineered scaffolds composed of nano-to sub-microscale fibers that simulate a native extracellular matrix. However, one major concern about electrospun scaffolds for tissue repair and regeneration is that their small pores defined by densely compacted fibers markedly hinder cell infiltration and tissue ingrowth. To address this problem, researchers have developed and investigated various methods of manipulating scaffold structures to increase pore size or loosen the scaffold. These methods involve the use of physical treatments, such as salt leaching, gas foaming and custom-made collectors, and combined techniques to obtain electrospun scaffolds with loose fibrous structures and large pores. This article provides a summary of these motivating electrospinning techniques to enhance cell infiltration of electrospun scaffolds, which may inspire new electrospinning techniques and their new biomedical applications.

Hydrogel as a bioactive material to regulate stem cell fate

Volume 1, Issue 1, September 2016, Pages 39-55
Yung Hao Tsou | Joe Khoneisser | Ping Chun Huang | Xiaoyang Xu

© 2016 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. The encapsulation of stem cells in a hydrogel substrate provides a promising future in biomedical applications. However, communications between hydrogels and stem cells is complicated; various factors such as porosity, different polymer types, stiffness, compatibility and degradation will lead to stem cell survival or death. Hydrogels mimic the three-dimensional extracellular matrix to provide a friendly environment for stem cells. On the other hand, stem cells can sense the surroundings to make the next progression, stretching out, proliferating or just to remain. As such, understanding the correlation between stem cells and hydrogels is crucial. In this Review, we first discuss the varying types of the hydrogels and stem cells, which are most commonly used in the biomedical fields and further investigate how hydrogels interact with stem cells from the perspective of their biomedical application, while providing insights into the design and development of hydrogels for drug delivery, tissue engineering and regenerative medicine purpose. In addition, we compare the results such as stiffness, degradation time and pore size as well as peptide types of hydrogels from respected journals.We also discussed most recently magnificent materials and their effects to regulate stem cell fate.

Bone grafts and biomaterials substitutes for bone defect repair: A review

Volume 2, Issue 4, December 2017, Pages 224-247
Wenhao Wang | Wenhao Wang | Kelvin W.K. Yeung | Kelvin W.K. Yeung

© 2017 The Authors Bone grafts have been predominated used to treat bone defects, delayed union or non-union, and spinal fusion in orthopaedic clinically for a period of time, despite the emergency of synthetic bone graft substitutes. Nevertheless, the integration of allogeneic grafts and synthetic substitutes with host bone was found jeopardized in long-term follow-up studies. Hence, the enhancement of osteointegration of these grafts and substitutes with host bone is considerably important. To address this problem, addition of various growth factors, such as bone morphogenetic proteins (BMPs), parathyroid hormone (PTH) and platelet rich plasma (PRP), into structural allografts and synthetic substitutes have been considered. Although clinical applications of these factors have exhibited good bone formation, their further application was limited due to high cost and potential adverse side effects. Alternatively, bioinorganic ions such as magnesium, strontium and zinc are considered as alternative of osteogenic biological factors. Hence, this paper aims to review the currently available bone grafts and bone substitutes as well as the biological and bio-inorganic factors for the treatments of bone defect.

Design strategies and applications of biomaterials and devices for Hernia repair

Volume 1, Issue 1, September 2016, Pages 2-17
Surge Kalaba | Ethan Gerhard | Joshua S. Winder | Eric M. Pauli | Randy S. Haluck | Jian Yang

© 2016 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. Hernia repair is one of the most commonly performed surgical procedures worldwide, with a multibillion dollar global market. Implant design remains a critical challenge for the successful repair and prevention of recurrent hernias, and despite significant progress, there is no ideal mesh for every surgery. This review summarizes the evolution of prostheses design toward successful hernia repair beginning with a description of the anatomy of the disease and the classifications of hernias. Next, the major milestones in implant design are discussed. Commonly encountered complications and strategies to minimize these adverse effects are described, followed by a thorough description of the implant characteristics necessary for successful repair. Finally, available implants are categorized and their advantages and limitations are elucidated, including non-absorbable and absorbable (synthetic and biologically derived) prostheses, composite prostheses, and coated prostheses. This review not only summarizes the state of the art in hernia repair, but also suggests future research directions toward improved hernia repair utilizing novel materials and fabrication methods.

The modulation of stem cell behaviors by functionalized nanoceramic coatings on Ti-based implants

Volume 1, Issue 1, September 2016, Pages 65-76
Xiangmei Liu | Man Li | Yizhou Zhu | K. W.K. Yeung | K. W.K. Yeung | Paul K. Chu | Shuilin Wu

© 2016 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. Nanoceramic coating on the surface of Ti-based metallic implants is a clinical potential option in orthopedic surgery. Stem cells have been found to have osteogenic capabilities. It is necessary to study the influences of functionalized nanoceramic coatings on the differentiation and proliferation of stem cells in vitro or in vivo. In this paper, we summarized the recent advance on the modulation of stem cells behaviors through controlling the properties of nanoceramic coatings, including surface chemistry, surface roughness and microporosity. In addition, mechanotransduction pathways have also been discussed to reveal the interaction mechanisms between the stem cells and ceramic coatings on Ti-based metals. In the final part, the osteoinduction and osteoconduction of ceramic coating have been also presented when it was used as carrier of BMPs in new bone formation.

Magnesium incorporated chitosan based scaffolds for tissue engineering applications

Volume 1, Issue 2, December 2016, Pages 132-139
Udhab Adhikari | Udhab Adhikari | Nava P. Rijal | Nava P. Rijal | Shalil Khanal | Shalil Khanal | Devdas Pai | Devdas Pai | Jagannathan Sankar | Jagannathan Sankar | Narayan Bhattarai | Narayan Bhattarai

© 2016 The Authors. Chitosan based porous scaffolds are of great interest in biomedical applications especially in tissue engineering because of their excellent biocompatibility in vivo, controllable degradation rate and tailorable mechanical properties. This paper presents a study of the fabrication and characterization of bioactive scaffolds made of chitosan (CS), carboxymethyl chitosan (CMC) and magnesium gluconate (MgG). Scaffolds were fabricated by subsequent freezing-induced phase separation and lyophilization of polyelectrolyte complexes of CS, CMC and MgG. The scaffolds possess uniform porosity with highly interconnected pores of 50-250 µm size range. Compressive strengths up to 400 kPa, and elastic moduli up to 5 MPa were obtained. The scaffolds were found to remain intact, retaining their original threedimensional frameworks while testing in in-vitro conditions. These scaffolds exhibited no cytotoxicity to 3T3 fibroblast and osteoblast cells. These observations demonstrate the efficacy of this new approach to preparing scaffold materials suitable for tissue engineering applications.

3D printing of Mg-substituted wollastonite reinforcing diopside porous bioceramics with enhanced mechanical and biological performances

Volume 1, Issue 1, September 2016, Pages 85-92
Dongshuang He | Chen Zhuang | Sanzhong Xu | Xiurong Ke | Xianyan Yang | Lei Zhang | Guojing Yang | Xiaoyi Chen | Xiaozhou Mou | An Liu | Zhongru Gou

© 2016 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. Mechanical strength and its long-term stability of bioceramic scaffolds is still a problem to treat the osteonecrosis of the femoral head. Considering the long-term stability of diopside (DIO) ceramic but poor mechanical strength, we developed the DIO-based porous bioceramic composites via dilute magnesium substituted wollastonite reinforcing and three-dimensional (3D) printing. The experimental results showed that the secondary phase (i.e. 10% magnesium substituting calcium silicate; CSM10) could readily improve the sintering property of the bioceramic composites (DIO/CSM10-x, x ¼ 0-30) with increasing the CSM10 content from 0% to 30%, and the presence of the CSM10 also improved the biomimetic apatite mineralization ability in the pore struts of the scaffolds. Furthermore, the flexible strength (12.5 e30 MPa) and compressive strength (14-37 MPa) of the 3D printed porous bioceramics remarkably increased with increasing CSM10 content, and the compressive strength of DIO/CSM10-30 showed a limited decay (from 37 MPa to 29 MPa) in the Tris buffer solution for a long time stage (8 weeks). These findings suggest that the new CSM10-reinforced diopside porous constructs possess excellent mechanical properties and can potentially be used to the clinic, especially for the treatment of osteonecrosis of the femoral head work as a bioceramic rod.

Characterization and corrosion property of nano-rod-like HA on fluoride coating supported on Mg-Zn-Ca alloy

Volume 2, Issue 2, June 2017, Pages 63-70
Yashan Feng | Shijie Zhu | Liguo Wang | Lei Chang | Bingbing Yan | Xiaozhe Song | Shaokang Guan

© 2017 The Authors. The poor corrosion resistance of biodegradable magnesium alloys is the dominant factor that limits their clinical application. In this study, to deal with this challenge, fluoride coating was prepared on MgeZn eCa alloy as the inner coating and then hydroxyapatite (HA) coating as the outer coating was deposited on fluoride coating by pulse reverse current electrodeposition (PRC-HA/MgF2). As a comparative study, the microstructure and corrosion properties of the composite coating with the outer coating fabricated by traditional constant current electrodeposition (TED-HA/MgF2) were also investigated. Scanning electron microscopy (SEM) images of the coatings show that the morphology of PRC-HA/MgF2coating is dense and uniform, and presents nano-rod-like structure. Compared with that of TED-HA/MgF2, the corrosion current density of Mg alloy coated with PRC-HA/MgF2coatings decreases from 5.72 × 10-5A/cm2to 4.32 × 10-7A/cm2, and the corrosion resistance increases by almost two orders of magnitude. In immersion tests, samples coated with PRC-HA/MgF2coating always show the lowest hydrogen evolution amount, and could induce deposition of the hexagonal structure-apatite on the surface rapidly. The results show that the corrosion resistance and the bioactivity of the coatings have been improved by adopting double-pulse current mode in the process of preparing HA on fluoride coating, and the PRC-HA/MgF2coating is worth of further investigation.

Titanium-niobium pentoxide composites for biomedical applications

Volume 1, Issue 2, December 2016, Pages 127-131
Yuncang Li | Khurram S. Munir | Jixing Lin | Jixing Lin | Cuie Wen

© 2016 The Authors. The strength of titanium scaffolds with the introduction of high porosity decreases dramatically and may become inadequate for load bearing in biomedical applications. To simultaneously meet the requirements of biocompatibility, low elastic modulus and appropriate strength for orthopedic implant materials, it is highly desirable to develop new biocompatible titanium based materials with enhanced strength. In this study, we developed a niobium pentoxide (Nb2O5) reinforced titanium composite via powder metallurgy for biomedical applications. The strength of the Nb2O5reinforced titanium composites (Ti-Nb2O5) is significantly higher than that of pure titanium. Cell culture results revealed that the Ti-Nb2O5composite exhibits excellent biocompatibility and cell adhesion. Human osteoblast-like cells grew and spread healthily on the surface of the Ti-Nb2O5composite. Our study demonstrated that Nb2O5reinforced titanium composite is a promising implant material by virtue of its high mechanical strength and excellent biocompatibility.

Molecular characterization and antibacterial effect of endophytic actinomycetes Nocardiopsis sp. GRG1 (KT235640) from brown algae against MDR strains of uropathogens

Volume 1, Issue 2, December 2016, Pages 140-150
Govindan Rajivgandhi | Ramachandran Vijayan | Ramachandran Vijayan | Marikani Kannan | Malairaja Santhanakrishnan | Natesan Manoharan

© 2016 The Authors. Our study is to evaluate the potential bioactive compound of Nocardiopsis sp. GRG1 (KT235640) and its antibacterial activity against multi drug resistant strains (MDRS) on urinary tract infections (UTIs). Two brown algae samples were collected and were subjected to isolation of endophytic actinomycetes. 100 strains of actinomycetes were isolated from algal samples based on observation of morphology and physiological characters. 40 strains were active in antagonistic activity against various clinical pathogens. Among the strains, 10 showed better antimicrobial activity against MDRS on UTIs. The secondary metabolite of Nocardiopsis sp. GRG1 (KT235640) has showed tremendous antibacterial activity against UTI pathogens compared to other strains. Influence of various growth parameters were used for synthesis of secondary metabolites, such as optimum pH 7, incubation time 5-7 days, temperature (30 °C), salinity (5%), fructose and mannitol as the suitable carbon and nitrogen sources. At 100 mg/ml concentration MIC of Nocardiopsis sp. GRG1 (KT235640) showed highest percentage of inhibition against Proteus mirabilis (85%), and E.coli, Staphylococcus auerues, Psuedomonas aeroginasa, Enterobactor sp and Coagulinase negative staphylococci 78-85% respectively.

Research of a novel biodegradable surgical staple made of high purity magnesium

Volume 1, Issue 2, December 2016, Pages 122-126
Hongliu Wu | Changli Zhao | Jiahua Ni | Shaoxiang Zhang | Jingyi Liu | Jun Yan | Yigang Chen | Xiaonong Zhang | Xiaonong Zhang

© 2016 The Authors. Surgical staples made of pure titanium and titanium alloys are widely used in gastrointestinal anastomosis. However the Ti staple cannot be absorbed in human body and produce artifacts on computed tomography (CT) and other imaging examination, and cause the risk of incorrect diagnosis. The bioabsorbable staple made from polymers that can degrade in human body environment, is an alternative. In the present study, biodegradable high purity magnesium staples were developed for gastric anastomosis. U-shape staples with two different interior angles, namely original 90° and modified 100°, were designed. Finite element analysis (FEA) showed that the residual stress concentrated on the arc part when the original staple was closed to B-shape, while it concentrated on the feet for the modified staple after closure. The in vitro tests indicated that the arc part of the original staple ruptured firstly after 7 days immersion, whereas the modified one kept intact, demonstrating residual stress greatly affected the corrosion behavior of the HP-Mg staples. The in vivo implantation showed good biocompatibility of the modified Mg staples, without inflammatory reaction 9 weeks post-operation. The Mg staples kept good closure to the Anastomosis, no leaking and bleeding were found, and the staples exhibited no fracture or severe corrosion cracks during the degradation.

Effects of external stress on biodegradable orthopedic materials: A review

Volume 1, Issue 1, September 2016, Pages 77-84
Xuan Li | Xuan Li | Chenglin Chu | Chenglin Chu | Paul K. Chu

© 2016 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. Biodegradable orthopedic materials (BOMs) are used in rehabilitation and reconstruction of fractured tissues. The response of BOMs to the combined action of physiological stress and corrosion is an important issue in vivo since stress-assisted degradation and cracking are common. Although the degradation behavior and kinetics of BOMs have been investigated under static conditions, stress effects can be very serious and even fatal in the dynamic physiological environment. Since stress is unavoidable in biomedical applications of BOMs, recent work has focused on the evaluation and prediction of the properties of BOMs under stress in corrosive media. This article reviews recent progress in this important area focusing on biodegradable metals, polymers, and ceramics.

Controlled release and biocompatibility of polymer/titania nanotube array system on titanium implants

Volume 2, Issue 1, March 2017, Pages 44-50
Tingting Wang | Zhengyang Weng | Xiangmei Liu | Kelvin W.K. Yeung | Haobo Pan | Shuilin Wu | Shuilin Wu

© 2017 The Authors. Bacterial infection and tissue inflammation are the major causes of early failure of titanium-based orthopedic implants; thus, surgical implants with tunable drug releasing properties represent an appealing way to address some of these problems of bacterial infection and tissue inflammation in early age of orthopedic implants. In this work, a hybrid surface system composed of biodegradable poly(lactic-coglycolic acid) (PLGA) and titania nanotubes (TNTs) has been successfully constructed on Ti implants with the aim of preventing bacterial infection via long-term drug release. By varying the size of the TNTs and the thickness of the polymer film, the drug release profile can be tuned to achieve the optimal therapeutic action throughout the treatment time. The size of TNTs plays a dominant role in the drug loading dose of TNTs/PLGA hybrid coatings. In this work, TNTs with an average size of 80 nm can achieve the largest loading dose. Depending on the polymer thickness, significant improvement in the drug release characteristics is attained, for instance, reduced burst release (from 84% to 27%) and overall release time extended from 5 to over 40 days. In addition, the PLGA layers may favor the proliferation and osteogenesis of MC3T3-E1 mouse cells at an earlier stage. Therefore, this TNT/PLGA hybrid surface system can be employed as an effective bioplatform for improving both self-antibacterial performance and biocompatibility of Ti-based biomaterials.

Incorporation of bioactive glass nanoparticles in electrospun PCL/chitosan fibers by using benign solvents

Volume 3, Issue 1, March 2018, Pages 55-63
Liliana Liverani | Jonas Lacina | Judith A. Roether | Elena Boccardi | Manuela S. Killian | Patrik Schmuki | Patrik Schmuki | Dirk W. Schubert | Aldo R. Boccaccini

© 2017 The Authors The use of bioactive glass (BG) particles as a filler for the development of composite electrospun fibers has already been widely reported and investigated. The novelty of the present research work is represented by the use of benign solvents (like acetic acid and formic acid) for electrospinning of composite fibers containing BG particles, by using a blend of PCL and chitosan. In this work, different BG particle sizes were investigated, namely nanosized and micron-sized. A preliminary investigation about the possible alteration of BG particles in the electrospinning solvents was performed using SEM analysis. The obtained composite fibers were investigated in terms of morphological, chemical and mechanical properties. An in vitro mineralization assay in simulated body fluid (SBF) was performed to investigate the capability of the composite electrospun fibers to induce the formation of hydroxycarbonate apatite (HCA).

Chitosan based metallic nanocomposite scaffolds as antimicrobial wound dressings

Volume 3, Issue 3, September 2018, Pages 267-277
Annapoorna Mohandas | S. Deepthi | Raja Biswas | R. Jayakumar

© 2017 The Authors Chitosan based nanocomposite scaffolds have attracted wider applications in medicine, in the area of drug delivery, tissue engineering and wound healing. Chitosan matrix incorporated with nanometallic components has immense potential in the area of wound dressings due to its antimicrobial properties. This review focuses on the different combinations of Chitosan metal nanocomposites such as Chitosan/nAg, Chitosan/nAu, Chitosan/nCu, Chitosan/nZnO and Chitosan/nTiO2towards enhancement of healing or infection control with special reference to the antimicrobial mechanism of action and toxicity.

Analysis of the in vitro degradation and the in vivo tissue response to bi-layered 3D-printed scaffolds combining PLA and biphasic PLA/bioglass components – Guidance of the inflammatory response as basis for osteochondral regeneration

Volume 2, Issue 4, December 2017, Pages 208-223
Mike Barbeck | Tiziano Serra | Patrick Booms | Sanja Stojanovic | Stevo Najman | Elisabeth Engel | Elisabeth Engel | Elisabeth Engel | Robert Sader | Charles James Kirkpatrick | Melba Navarro | Shahram Ghanaati

© 2017 The Authors The aim of the present study was the in vitro and in vivo analysis of a bi-layered 3D-printed scaffold combining a PLA layer and a biphasic PLA/bioglass G5 layer for regeneration of osteochondral defects in vivo Focus of the in vitro analysis was on the (molecular) weight loss and the morphological and mechanical variations after immersion in SBF. The in vivo study focused on analysis of the tissue reactions and differences in the implant bed vascularization using an established subcutaneous implantation model in CD-1 mice and established histological and histomorphometrical methods. Both scaffold parts kept their structural integrity, while changes in morphology were observed, especially for the PLA/G5 scaffold. Mechanical properties decreased with progressive degradation, while the PLA/G5 scaffolds presented higher compressive modulus than PLA scaffolds. The tissue reaction to PLA included low numbers of BMGCs and minimal vascularization of its implant beds, while the addition of G5 lead to higher numbers of BMGCs and a higher implant bed vascularization. Analysis revealed that the use of a bi-layered scaffold shows the ability to observe distinct in vivo response despite the physical proximity of PLA and PLA/G5 layers. Altogether, the results showed that the addition of G5 enables to reduce scaffold weight loss and to increase mechanical strength. Furthermore, the addition of G5 lead to a higher vascularization of the implant bed required as basis for bone tissue regeneration mediated by higher numbers of BMGCs, while within the PLA parts a significantly lower vascularization was found optimally for chondral regeneration. Thus, this data show that the analyzed bi-layered scaffold may serve as an ideal basis for the regeneration of osteochondral tissue defects. Additionally, the results show that it might be able to reduce the number of experimental animals required as it may be possible to analyze the tissue response to more than one implant in one experimental animal.

Melt electrospinning of daunorubicin hydrochloride-loaded poly (ε-caprolactone) fibrous membrane for tumor therapy

Volume 2, Issue 2, June 2017, Pages 96-100
He Lian | Zhaoxu Meng

© 2017 The Authors. Daunorubicin hydrochloride is a cell-cycle non-specific antitumor drug with a high therapeutic effect. The present study outlines the fabrication of daunorubicin hydrochloride-loaded poly (ε-caprolactone) (PCL) fibrous membranes by melt electrospinning for potential application in localized tumor therapy. The diameters of the drug-loaded fibers prepared with varying concentrations of daunorubicin hydrochloride (1, 5, and 10 wt%) were 2.48 ± 1.25, 2.51 ± 0.78, and 2.49 ± 1.58 mm, respectively. Fluorescence images indicated that the hydrophobic drug was dispersed in the hydrophilic PCL fibers in their aggregated state. The drug release profiles of the drug-loaded PCL melt electrospun fibrous membranes were approximately linear, with slow release rates and long-term release periods, and no observed burst release. The MTT assay was used to examine the cytotoxic effect of the released daunorubicin hydrochloride on HeLa and glioma cells (U87) in vitro. The inhibition ratios of HeLa and glioma cells following treatment with membranes prepared with 1, 5, and 10 wt% daunorubicin hydrochloride were 62.69%, 76.12%, and 85.07% and 62.50%, 77.27%, and 84.66%, respectively. Therefore, PCL melt electrospun fibrous membranes loaded with daunorubicin hydrochloride may be used in the local administration of oncotherapy.

Smart biomaterials: Surfaces functionalized with proteolytically stable osteoblast-adhesive peptides

Volume 2, Issue 3, September 2017, Pages 121-130
Annj Zamuner | Paola Brun | Michele Scorzeto | Giuseppe Sica | Ignazio Castagliuolo | Monica Dettin

© 2017 The Authors Engineered scaffolds for bone tissue regeneration are designed to promote cell adhesion, growth, proliferation and differentiation. Recently, covalent and selective functionalization of glass and titanium surfaces with an adhesive peptide (HVP) mapped on [351–359] sequence of human Vitronectin allowed to selectively increase osteoblast attachment and adhesion strength in in vitro assays, and to promote osseointegration in in vivo studies. For the first time to our knowledge, in this study we investigated the resistance of adhesion sequences to proteolytic digestion: HVP was completely cleaved after 5 h. In order to overcome the enzymatic degradation of the native peptide under physiological conditions we synthetized three analogues of HVP sequence. A retro-inverted peptide D-2HVP, composed of D amino acids, was completely stable in serum-containing medium. In addition, glass surfaces functionalized with D-2HVP increased human osteoblast adhesion as compared to the native peptide and maintained deposition of calcium. Interestingly, D-2HVP increased expression of IBSP, VTN and SPP1 genes as compared to HVP functionalized surfaces. Total internal reflection fluorescence microscope analysis showed cells with numerous filopodia spread on D-2HVP-functionalized surfaces. Therefore, the D-2HVP sequence is proposed as new osteoblast adhesive peptide with increased bioactivity and high proteolytic resistance.

The development of collagen based composite scaffolds for bone regeneration

Volume 3, Issue 1, March 2018, Pages 129-138
Dawei Zhang | Xiaowei Wu | Jingdi Chen | Kaili Lin

© 2017 The Authors Bone is consisted of bone matrix, cells and bioactive factors, and bone matrix is the combination of inorganic minerals and organic polymers. Type I collagen fibril made of five triple-helical collagen chains is the main organic polymer in bone matrix. It plays an important role in the bone formation and remodeling process. Moreover, collagen is one of the most commonly used scaffold materials for bone tissue engineering due to its excellent biocompatibility and biodegradability. However, the low mechanical strength and osteoinductivity of collagen limit its wider applications in bone regeneration field. By incorporating different biomaterials, the properties such as porosity, structural stability, osteoinductivity, osteogenicity of collagen matrixes can be largely improved. This review summarizes and categorizes different kinds of biomaterials including bioceramic, carbon and polymer materials used as components to fabricate collagen based composite scaffolds for bone regeneration. Moreover, the possible directions of future research and development in this field are also proposed.

3D additive-manufactured nanocomposite magnetic scaffolds: Effect of the application mode of a time-dependent magnetic field on hMSCs behavior

Volume 2, Issue 3, September 2017, Pages 138-145
Ugo D'Amora | Teresa Russo | Antonio Gloria | Virginia Rivieccio | Vincenzo D'Antò | Vincenzo D'Antò | Giacomo Negri | Luigi Ambrosio | Roberto De Santis

© 2017 The Authors Over the past few years, the influence of static or dynamic magnetic fields on biological systems has become a topic of considerable interest. Magnetism has recently been implicated to play significant roles in the regulation of cell responses and, for this reason, it is revolutionizing many aspects of healthcare, also suggesting new opportunities in tissue engineering. The aim of the present study was to analyze the effect of the application mode of a time-dependent magnetic field on the behavior of human mesenchymal stem cells (hMSCs) seeded on 3D additive-manufactured poly(ɛ-caprolactone)/iron-doped hydroxyapatite (PCL/FeHA) nanocomposite scaffolds.

Human adipose derived stem cells are superior to human osteoblasts (HOB) in bone tissue engineering on a collagen-fibroin-ELR blend

Volume 2, Issue 2, June 2017, Pages 71-81
Esen Sayin | Esen Sayin | Rosti Hama Rashid | José Carlos Rodríguez-Cabello | Ahmed Elsheikh | Erkan Türker Baran | Vasif Hasirci | Vasif Hasirci | Vasif Hasirci

© 2017 The Authors. The ultrastructure of the bone provides a unique mechanical strength against compressive, torsional and tensional stresses. An elastin-like recombinamer (ELR) with a nucleation sequence for hydroxyapatite was incorporated into films prepared from a collagen e silk fibroin blend carrying microchannel patterns to stimulate anisotropic osteogenesis. SEM and fluorescence microscopy showed the alignment of adipose-derived stem cells (ADSCs) and the human osteoblasts (HOBs) on the ridges and in the grooves of microchannel patterned collagen-fibroin-ELR blend films. The Young's modulus and the ultimate tensile strength (UTS) of untreated films were 0.58 ± 0.13 MPa and 0.18 ± 0.05 MPa, respectively. After 28 days of cell culture, ADSC seeded film had a Young's modulus of 1.21 ± 0.42 MPa and UTS of 0.32 ± 0.15 MPa which were about 3 fold higher than HOB seeded films. The difference in Young's modulus was statistically significant (p: 0.02). ADSCs attached, proliferated and mineralized better than the HOBs. In the light of these results, ADSCs served as a better cell source than HOBs for bone tissue engineering of collagen-fibroin-ELR based constructs used in this study. We have thus shown the enhancement in the tensile mechanical properties of the bone tissue engineered scaffolds by using ADSCs.

Comparative investigations of structure and properties of micro-arc wollastonite-calcium phosphate coatings on titanium and zirconium-niobium alloy

Volume 2, Issue 3, September 2017, Pages 177-184
M. B. Sedelnikova | E. G. Komarova | Yu P. Sharkeev | Yu P. Sharkeev | T. V. Tolkacheva | I. A. Khlusov | I. A. Khlusov | I. A. Khlusov | L. S. Litvinova | K. A. Yurova | V. V. Shupletsova

© 2017 The Authors Investigation results of micro-arc wollastonite–calcium phosphate (W–CaP) biocoatings on the pure titanium (Ti) and Zr–1wt.%Nb (Zr–1Nb) alloy were presented. The voltages of 150–300 V generate the micro-arc oxidation (MAO) process with the initial amplitude current of 150–550 A and 100–350 A for Ti and Zr–1Nb substrates, respectively. The identical dependencies of changes of the coating thickness, surface roughness and adhesion strength on the process voltage were revealed for the both substrates. The W–CaP coatings with the thickness of 10–11 μm were formed on Ti and Zr–1Nb under the low process voltage of 130–150 V. Elongated wollastonite particles with the size in the range of 40–100 μm were observed in such coatings. The structure of the coatings on Ti was presented by the X–ray amorphous and crystalline phases. The X–ray reflexes relating to the crystalline phases of Ti and wollastonite were observed only in XRD patterns of the coatings deposited under 130–200 V on Ti. While, the crystalline structure with phases of CaZr4(PO4)6, β–ZrP2O7, ZrO2, and Zr was detected in the coatings on Zr–1Nb. FT–IRS, XRD, SEM, and TEM data confirmed that the increase of the process voltage to 300 V leads to the dissociation of the wollastonite. No toxic effect of specimens on a viability, morphology and motility of human adipose–derived multipotent mesenchymal stem cells was revealed in vitro.

RF magnetron-sputtered coatings deposited from biphasic calcium phosphate targets for biomedical implant applications

Volume 2, Issue 3, September 2017, Pages 170-176
K. A. Prosolov | K. A. Prosolov | K. S. Popova | O. A. Belyavskaya | J. V. Rau | K. A. Gross | A. Ubelis | Yu P. Sharkeev | Yu P. Sharkeev

© 2017 The Authors Bioactive calcium phosphate coatings were deposited by radio-frequency magnetron sputtering from biphasic targets of hydroxyapatite and tricalcium phosphate, sintered at different mass % ratios. According to Raman scattering and X-ray diffraction data, the deposited hydroxyapatite coatings have a disordered structure. High-temperature treatment of the coatings in air leads to a transformation of the quasi-amorphous structure into a crystalline one. A correlation has been observed between the increase in the Ca content in the coatings and a subsequent decrease in Ca in the biphasic targets after a series of deposition processes. It was proposed that the addition of tricalcium phosphate to the targets would led to a finer coating's surface topography with the average size of 78 nm for the structural elements.

Biomaterial property-controlled stem cell fates for cardiac regeneration

Volume 1, Issue 1, September 2016, Pages 18-28
Yanyi Xu | Jianjun Guan

© 2016 The Authors. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. Myocardial infarction (MI) affects more than 8 million people in the United States alone. Due to the insufficient regeneration capacity of the native myocardium, one widely studied approach is cardiac tissue engineering, in which cells are delivered with or without biomaterials and/or regulatory factors to fully regenerate the cardiac functions. Specifically, in vitro cardiac tissue engineering focuses on using biomaterials as a reservoir for cells to attach, as well as a carrier of various regulatory factors such as growth factors and peptides, providing high cell retention and a proper microenvironment for cells to migrate, grow and differentiate within the scaffolds before implantation. Many studies have shown that the full establishment of a functional cardiac tissue in vitro requires synergistic actions between the seeded cells, the tissue culture condition, and the biochemical and biophysical environment provided by the biomaterials-based scaffolds. Proper electrical stimulation and mechanical stretch during the in vitro culture can induce the ordered orientation and differentiation of the seeded cells. On the other hand, the various scaffolds biochemical and biophysical properties such as polymer composition, ligand concentration, biodegradability, scaffold topography and mechanical properties can also have a significant effect on the cellular processes.

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