Silk fibroin/collagen protein hybrid cell-encapsulating hydrogels with tunable gelation and improved physical and biological properties

Buitrago, Jennifer O.,Patel, Kapil D.,El-Fiqi, Ahmed,Lee, Jung-Hwan,Kundu, Banani,Lee, Hae-Hyoung,Kim, Hae-Won Elsevier 2018 ACTA BIOMATERIALIA Vol.69 No.-

<P><B>Abstract</B></P> <P>Cell encapsulating hydrogels with tunable mechanical and biological properties are of special importance for cell delivery and tissue engineering. Silk fibroin and collagen, two typical important biological proteins, are considered potential as cell culture hydrogels. However, both have been used individually, with limited properties (<I>e.g.,</I> collagen has poor mechanical properties and cell-mediated shrinkage, and silk fibroin from <I>Bombyx mori (mulberry)</I> lacks cell adhesion motifs). Therefore, the combination of them is considered to achieve improved mechanical and biological properties with respect to individual hydrogels. Here, we show that the cell-encapsulating hydrogels of mulberry silk fibroin / collagen are implementable over a wide range of compositions, enabled simply by combining the different gelation mechanisms. Not only the gelation reaction but also the structural characteristics, consequently, the mechanical properties and cellular behaviors are accelerated significantly by the silk fibroin / collagen hybrid hydrogel approach. Of note, the mechanical and biological properties are tunable to represent the combined merits of individual proteins. The shear storage modulus is tailored to range from 0.1 to 20 kPa along the iso-compositional line, which is considered to cover the matrix stiffness of soft-to-hard tissues. In particular, the silk fibroin / collagen hydrogels are highly elastic, exhibiting excellent resistance to permanent deformation under different modes of stress; without being collapsed or water-squeezed out (<I>vs.</I> not possible in individual proteins) – which results from the mechanical synergism of interpenetrating networks of both proteins. Furthermore, the role of collagen protein component in the hybrid hydrogels provides adhesive sites to cells, stimulating anchorage and spreading significantly with respect to mulberry silk fibroin gel, which lacks cell adhesion motifs. The silk fibroin / collagen hydrogels can encapsulate cells while preserving the viability and growth over a long 3D culture period. Our findings demonstrate that the silk / collagen hydrogels possess physical and biological properties tunable and significantly improved (<I>vs.</I> the individual protein gels), implying their potential uses for cell delivery and tissue engineering.</P> <P><B>Statement of Significance</B></P> <P>Development of cell encapsulating hydrogels with excellent physical and biological properties is important for the cell delivery and cell-based tissue engineering. Here we communicate for the first time the novel protein composite hydrogels comprised of ‘Silk’ and ‘Collagen’ and report their outstanding physical, mechanical and biological properties that are not readily achievable with individual protein hydrogels. The properties include i) gelation accelerated over a wide range of compositions, ii) stiffness levels covering 0.1 kPa to 20 kPa that mimic those of soft-to-hard tissues, iii) excellent elastic behaviors under various stress modes (bending, twisting, stretching, and compression), iv) high resistance to cell-mediated gel contraction, v) rapid anchorage and spreading of cells, and vi) cell encapsulation ability with a long-term survivability. These results come from the synergism of individual proteins of alpha-helix and beta-sheet structured networks. We consider the current elastic cell-encapsulating hydrogels of silk-collagen can be potentially useful for the cell delivery and tissue engineering in a wide spectrum of soft-to-hard tissues.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Soft Power in emerging economies: A partial least squares – structural equation modeling exploratory analysis of the effects on outward foreign direct investment

Buitrago R. Ricardo E.,Rajasekar James,Alcaraz Jorge 한국외국어대학교 국제지역연구센터 2023 International Area Studies Review Vol.26 No.3

This article discusses the linkage between Soft Power institutional conditions and their effects on inward foreign direct investment (IFDI) as a mediator of outward foreign direct investment (OFDI). We measured Soft Power through the use of selected indicators between 2016 and 2019. To evaluate the proposed Soft Power constructs and their relationship with IFDI – OFDI, we applied partial least squares – structural equation modeling (PLS-SEM) analysis. The model outcomes suggest that Government, Business, Culture, and Diplomacy conditions have a significant and positive effect on IFDI and OFDI. The findings are context-moderated due to the heterogeneity of the emerging economies evaluated.

Core-shell fibrous stem cell carriers incorporating osteogenic nanoparticulate cues for bone tissue engineering

Olmos Buitrago, J.,Perez, R.A.,El-Fiqi, A.,Singh, R.K.,Kim, J.H.,Kim, H.W. Elsevier BV 2015 ACTA BIOMATERIALIA Vol.28 No.-

Moldable hydrogels that incorporate stem cells hold great promise for tissue engineering. They secure the encapsulated cells for required periods while allowing a permeable exchange of nutrients and gas with the surroundings. Core-shell fibrous structured hydrogel system represents these properties relevant to stem cell delivery and defect-adjustable tissue engineering. A designed dual concentric nozzle is used to simultaneously deposit collagen and alginate with a core-shell structured continuous fiber form in the ionic calcium bath. We aimed to impart extrinsic osteogenic cues in the nanoparticulate form, i.e., bioactive glass nanoparticles (BGn), inside the alginate shell, while encapsulating rat mesenchymal stem cells in the collagen core. Ionic measurement in aqueous solution indicated a continuous release of calcium ions from the BGn-added and -free scaffolds, whereas silicon was only released from the BGn-containing scaffolds. The presence of BGn allowed higher number of cells to migrate into the scaffolds when implanted in subcutaneous tissues of rat. Cell viability was preserved in the presence of the BGn, with no significant differences noticed from the control. The presence of BGn enhanced the osteogenic differentiation of the encapsulated rat mesenchymal stem cells, presenting higher levels of alkaline phosphatase activity as well as bone related genes, including collagen type I, bone sialoprotein and osteocalcin. Taken together, the incorporated BGn potentiated the capacity of the core-shell fibrous hydrogel system to deliver stem cells targeting bone tissue engineering.

Short- and long-term deflections of RC building structures influenced by construction processes

Yezid A. Alvarado,Manuel Buitrago,Isabel Gasch,María N. Domínguez,Miguel A. Cipagauta 국제구조공학회 2017 Structural Engineering and Mechanics, An Int'l Jou Vol.64 No.2

This paper analyzes the influence of the construction process on short- and long-term deflections on a reinforced concrete structure poured on-site by a portable industrialized system. A parametric analysis was carried out by the Finite Elements Method (FEM) that considered: a) type of construction process with reshoring or clearing (partial striking); b) the number of successively shored floors and c) the number of shores used on each floor. All three factors were especially important for the values of short- and long-term deflections, which were highest in the reshoring processes with the lowest number of successively shored floors and the lowest number of shores per floor. Deflections obtained were compared with the limits laid down by ACI 318-14 and as calculated by this code’s simplified method. The long-term deflections were seen to be almost double than those obtained by applying the ACI 318-14 code’s simplified method and in some cases these deflections were above the established limits. It can thus be concluded that the load history of a building under construction should be taken into account in order to satisfy a structure’s in-service conditions and durability.

Biomimetically grown apatite spheres from aggregated bioglass nanoparticles with ultrahigh porosity and surface area imply potential drug delivery and cell engineering applications

El-Fiqi, Ahmed,Buitrago, Jennifer O.,Yang, Sung Hee,Kim, Hae-Won Elsevier 2017 Acta Biomaterialia: structure-property-function re Vol.60 No.-

<P><B>Abstract</B></P> <P>Here we communicate the generation of biomimetically grown apatite spheres from aggregated bioglass nanoparticles and the potential properties applicable for drug delivery and cell/tissue engineering. Ion releasing nanoparticulates of bioglass (85%SiO<SUB>2</SUB>-15%CaO) in a mineralizing medium show an intriguing dynamic phenomenon – aggregation, mineralization to apatite, integration and growth into micron-sized (1.5–3μm) spheres. During the progressive ionic dissolution/precipitation reactions, nano-to-micro-morphology, glass-to-crystal composition, and the physico-chemical properties (porosity, surface area, and charge) change dynamically. With increasing reaction period, the apatite becomes more crystallized with increased crystallinity and crystal size, and gets a composition closer to the stoichiometry. The developed microspheres exhibit hierarchical surface nanostructure, negative charge (ς-potential of −20mV), and ultrahigh mesoporosity (mesopore size of 6.1nm, and the resultant surface area of 63.7m<SUP>2</SUP>/g and pore volume of 0.153cm<SUP>3</SUP>/g) at 14days of mineralization, which are even higher than those of its precursor bioglass nanoparticles. Thanks to these properties, the biomimetic mineral microspheres take up biological molecules effectively, <I>i.e.</I>, loading capacity of positive-charged protein is over 10%. Of note, the release is highly sustainable at a constant rate, <I>i.e.</I>, profiling almost ‘zero-order’ kinetics for 4weeks, suggesting the potential usefulness as protein delivery systems. The biomimetic mineral microspheres hold some remnant Si in the core region, and release calcium, phosphate, and silicate ions over the test period, implying the long-term ionic-related therapeutic functions. The mesenchymal stem cells favour the biomimetic spheres with an excellent viability. Due to the merit of sizes (a few micrometers), the spheres can be intercalated into cells, mediating cellular interactions in 3D cell-spheroid engineering, and also can stimulate osteogenic differentiation of cells when incorporated into cell-laden gels. The intriguing properties observed in this study, including biomimetic composition, high mesoporosity, release of therapeutic ions, effective loading and long-term release of proteins, and diverse yet favorable 3D cellular interactions, suggest great potential of the newly developed biomimetic microspheres in biomedical applications, such as drug delivery and cell/tissue engineering.</P> <P><B>Statement of Significance</B></P> <P>This work reports the generation of apatite spheres with a few micrometers in size biomimetically grown from bioactive glass nanoparticles, through a series of intriguing yet unprecedented phenomenon involving aggregation of nanoparticles, mineralization and sphere growth. The mineral microspheres possess some unique physico-chemical properties including mesoporosity, ultrahigh surface area, and therapeutic ionic release. Furthermore, the spheres show excellent loading and delivery capacity of protein molecules, and mediate favorable cellular interactions in 2D and 3D culture conditions, demonstrating a future multifunctional microcarrier platform for the therapeutics delivery and cell/tissue engineering.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Silk based hydrogel for tunable physical and biological properties

Ji-Young Yoon,Sungmin Park,Jennifer O. Buitrago,Kapil D. Patel,Ahmed El-Fiqi,Jung-Hwan Lee,Banani Kundu,Hae-Hyoung Lee,Hae-Won Kim 대한치과재료학회 2018 대한치과기재학회 학술대회 Vol.2018 No.4

Novel therapeutic core-shell hydrogel scaffolds with sequential delivery of cobalt and bone morphogenetic protein-2 for synergistic bone regeneration

Perez, R.A.,Kim, J.H.,Buitrago, J.O.,Wall, I.B.,Kim, H.W. Elsevier BV 2015 ACTA BIOMATERIALIA Vol.23 No.-

Enabling early angiogenesis is a crucial issue in the success of bone tissue engineering. Designing scaffolds with therapeutic potential to stimulate angiogenesis as well as osteogenesis is thus considered a promising strategy. Here, we propose a novel scaffold designed to deliver angiogenic and osteogenic factors in a sequential manner to synergize the bone regeneration event. Hydrogel fibrous scaffolds comprised of a collagen-based core and an alginate-based shell were constructed. Bone morphogenetic protein 2 (BMP2) was loaded in the core, while the shell incorporated Co ions, enabled by the alginate crosslinking in CoCl<SUB>2</SUB>/CaCl<SUB>2</SUB> solution. The incorporation of Co ions was tunable by altering the concentration of Co ions in the crosslinking solution. The incorporated Co ions, that are known to play a role in angiogenesis, were released rapidly within a week, while the BMP2, acting as an osteogenic factor, was released in a highly sustainable manner over several weeks to months. The release of Co ions significantly up-regulated the in vitro angiogenic properties of cells, including the expression of angiogenic genes (CD31, VEGF, and HIF-1α), secretion of VEGF, and the formation of tubule-like networks. However, BMP2 did not activate the angiogenic processes. Osteogenesis was also significantly enhanced by the release of Co ions as well as BMP2, characterized by higher expression of osteogenic genes (OPN, ALP, BSP, and OCN), and OCN protein secretion. An in vivo study on the designed scaffolds implanted in rat calvarium defect demonstrated significantly enhanced bone formation, evidenced by new bone volume and bone density, due to the release of BMP2 and Co ions. This is the first study using Co ions as an angiogenic element together with the osteogenic factor BMP2 within scaffolds, and the results demonstrated the possible synergistic role of Co ions with BMP2 in the bone regeneration process, suggesting a novel potential therapeutic scaffold system. Statement of Significance: This is the first report that utilizes Co ion as a pro-angiogenic factor in concert with osteogenic factor BMP-2 in the fine-tuned core-shell hydrogel fiber scaffolds, and ultimately achieves osteo/angiogenesis of MSCs and bone regeneration through the sequential delivery of both biofactors. This novel approach facilitates a new class of therapeutic scaffolds, aiming at successful bone regeneration with the help of angiogenesis.

Angiogenesis-promoted vessel formation with silicate shelled hydrogel fiber scaffolds

Oyunchimeg Bayaraa,Khandmaa Dashnyam,Jennifer O. Buitrago,Nandin Mandakhbayar,Jonathan C. Knowles,Jung-Hwan Lee,Hae-Won Kim 대한치과재료학회 2019 대한치과기재학회 학술대회 Vol.2019 No.11

Silk fibroin/collagen hybrid hydrogel for cell encapsulating hydrogels with tunable gelation and improved physical and biological properties

Ji-Won Jung,Jennifer O. Buitrago,Jung-Hwan Lee,Hae-Hyoung Lee,Hae-Won Kim 대한치과재료학회 2019 대한치과기재학회 학술대회 Vol.2019 No.11

Dynamic punching shear tests of flat slab-column joints with 5D steel fibers

Yezid A. Alvarado,Benjamín Torres,Manuel Buitrago,Daniel M. Ruiz,Sergio Y. Torres,Ramón A. Álvarez 국제구조공학회 2022 Structural Engineering and Mechanics, An Int'l Jou Vol.81 No.3

This study aimed to analyze the dynamic punching shear performance of slab-column joints under cyclic loads with the use of double-hooked end (5D) steel fibers. Structural systems such as slab-column joints are widely found in infrastructures. The susceptibility to collapse of such structures when submitted to seismic loads is highly dependent on the structural performance of the slab-column connections. For this reason, the punching capacity of reinforced concrete (RC) structures has been the subject of a great number of studies. Steel fibers are used to achieve a certain degree of ductility under seismic loads. In this context, 5D steel hooked fibers provide high levels of fiber anchoring, tensile strength and ductility. However, only limited research has been carried out on the performance under cyclic loads of concrete structural members containing steel fibers. This study covers this gap with experimental testing of five different full-scale subassemblies of RC slab-column joints: one without punching reinforcement, one with conventional punching reinforcement and three with 5D steel fibers. The subassemblies were tested under cyclic loading, which consisted of applying increasing lateral displacement cycles, such as in seismic situations, with a constant axial load on the column. This set of cycles was repeated for increasing axial loads on the column until failure. The results showed that 5D steel fiber subassemblies: i) had a greater capacity to dissipate energy, ii) improved punching shear strength and stiffness degradation under cyclic loads; and iii) increased cyclic loading capacity.