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RISS 인기검색어
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- 저자 : Roman A. Perez (검색결과 17 건)
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Biomaterials control of pluripotent stem cell fate for regenerative therapy
Perez, Roman A.,Choi, Seong-Jun,Han, Cheol-Min,Kim, Jung-Ju,Shim, Hosup,Leong, Kam W.,Kim, Hae-Won Elsevier 2016 Progress in materials science Vol.82 No.-
<P>Pluripotent stem cells (PSCs) derived from either the embryo or reprogramming processes have the capacity to self-renew and differentiate into various cells in the body, thereby offering a valuable cell source for regenerative therapy of intractable disease and serious tissue damage. Traditionally, methods to expand and differentiate PSCs have been confined to 2D culture through the use of biochemical signals; the use of biomaterials beyond the commercially available culture dish has not been widespread. Nevertheless, biomaterials with tailored physical, chemical, and geometrical cues can mimic the native stem cell niche to tune the microenvironmental conditions for PSCs to preserve their self-renewal capacity or to switch their phenotype, a status ultimately needed to gain regenerative functions ex vivo and in vivo. Recently efforts to explore biomaterials to regulate PSC behavior have accelerated. The biomaterials properties investigated include surface chemistry, immobilized ligand, nano-/micro-topography, matrix stiffness, geometrical complexity, 3D configuration, and combinations thereof. This review aims to cover the current advances of biomaterials-based control over PSCs, particularly for the preservation of self-renewal capacity as well as for their differentiation into target cells. Furthermore, it aims to suggest future research directions that would facilitate the eventual translation of these advances. (C) 2016 Elsevier Ltd. All rights reserved.</P>
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Perez, Roman A.,Kim, Tae‐,Hyun,Kim, Meeju,Jang, Jun‐,Hyeog,Ginebra, Maria‐,Pau,Kim, Hae‐,Won Wiley Subscription Services, Inc., A Wiley Company 2013 Journal of biomedical materials research. Part A Vol.101 No.4
<P><B>Abstract</B></P><P>Combining calcium phosphate cements (CPCs) with bioactive molecules improves their bone regeneration potential. Although CPCs are highly osteoconductive, sometimes they have limited biological responses, especially in terms of cell proliferation. Here, we used basic fibroblast growth factor (bFGF) in an α‐tricalcium phosphate cement with different initial powder sizes (coarse vs. fine; designated as CPC‐C and CPC‐F, respectively) and investigated the behavior of bFGF loading and release, as well as the effects on osteoblast responses. bFGF was loaded at 10 μg/ml or 25 μg/ml onto the set form of two types of CPCs, aiming to allow penetration into the pore structure and adsorption onto the cement crystallites. The CPC formulated with fine powder (CPC‐F) had higher specific surface area and smaller‐sized pores and retained slightly higher amounts of bFGF within the structure. The bFGF release study performed for 3 weeks showed a sustained‐release profile; after an initial rapid release over approximately 3 days, further release pattern was almost linear. Compared to CPC‐F, CPC‐C showed a much faster release pattern. The effects of the bFGF incorporation within CPCs on cellular responses were assessed in terms of cell proliferation using MC3T3‐E1 pre‐osteoblastic cells. Compared with bFGF‐free CPCs (both CPC‐C and CPC‐F), those containing bFGF stimulated cell proliferation for up to 7 days. An inhibition study of bFGF receptor demonstrated that the improvement of cell proliferation resulted from the role of bFGF released from the CPCs. This study provides beneficial information on improving the biological properties of CPCs by combining them with specific therapeutic molecules, and particularly with bFGF, showing that the cell proliferative ability was significantly stimulated, which may have potential applications for further use in stem cell‐based bone tissue engineering. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.</P>
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Kim Tae-Woo,Ahn Woo-Beom,Kim Joong-Min,Kim Joong-Hyun,Kim Tae-Hyun,Perez Roman A.,Jang Hyon-Seok 한국조직공학과 재생의학회 2020 조직공학과 재생의학 Vol.17 No.5
Background: The delivery of growth factors using a carrier system presents a promising and innovative tool in tissue engineering and dentistry today. Two of the foremost bioactive factors, bone morphogenetic protein-2 and vascular endothelial growth factor (VEGF), are widely applied using a ceramic scaffold. The aim of this study was to determine the use of hydroxyapatite microcarrier (MC) for dual delivery of osteogenic and angiogenic factors to accelerate hard tissue regeneration during the regenerative process. Methods: Two MCs of different sizes were fabricated by emulsification of gelatin and alpha-tricalcium phosphate (α-TCP). The experimental group was divided based on the combination of MC size and growth factors. For investigating the in vitro properties, rat mesenchymal stem cells (rMSCs) were harvested from bone marrow of the femur and tibia. For in vivo experiments, MC with/without growth factors was applied into the standardized, 5-mm diameter defects, which were made bilaterally on the parietal bone of the rat. The animals were allowed to heal for 8 weeks, and samples were harvested and analyzed by micro-computed tomography and histology. Results: Improved proliferation of rat mesenchymal stem cells was observed with VEGF loaded MC. For osteogenic differentiation, dual growth factors delivered by MC showed higher osteogenic gene expression, alkaline phosphatse production and calcium deposition. The in vivo results revealed statistically significant increase in new bone formation when dual growth factors were delivered by MC. Dual growth factors administered on a calcium phosphate matrix showed significantly enhanced osteogenic potential. Conclusion: We propose this system has potential clinical utility in providing solutions for craniofacial bone defects, with the added benefit of early availability.
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El-Fiqi, Ahmed,Kim, Joong-Hyun,Perez, Roman A.,Kim, Hae-Won Royal Society of Chemistry 2015 Journal of Materials Chemistry B Vol. No.
<P>Injectable calcium phosphate cements (CPCs) with strong mechanical properties and improved biological performance have the potential to be extensively used for bone regeneration. Although many additive materials have been incorporated into CPCs in order to achieve improvements in their mechanical and biological properties, somehow the results have not been fully satisfactory. Here we focus on using the nanoparticle form of mesoporous bioactive glasses (mBGn) as additive nano-components for alpha-tricalcium phosphate-based CPCs. The effects of mBGn incorporated up to 10 wt% into CPCs were examined in depth with respect to the setting time, morphology, injectability, wash-out properties, consistency, ionic release, pH change, and mechanical strength. The addition of mBGn significantly increased the surface area (for both the as-cemented and the hydrated compositions) and also significantly accelerated the setting reaction of CPCs. The injectability and the anti-washout property of CPCs were remarkably enhanced with the addition of mBGn. In striking contrast to the case of pure CPCs, the morphological changes observed in simulated body fluid (SBF) revealed a spherical development of apatite crystals, replicating the nanospherical morphology of the mBGn and consequently resulting in a nano-micro-roughened surface. The mechanical compressive strength substantially increased after SBF immersion and significantly higher values were recorded for mBGn/CPC as compared to pure CPCs. The ion release, including that of calcium, phosphate, and silicon, was recorded at substantial levels during the test period, and the addition of mBGn caused changes in the pH towards less acidic. The <I>in vivo</I> study of the mBGn/CPCs in rat subcutaneous tissue confirmed excellent tissue compatibility with little evidence of inflammatory reactions while exhibiting viable fibroblastic cells with a substantial presence of mature endothelial cells surrounding the cements. When implanted in a rat calvarium defect, a substantial degradation of the samples was noticed in the interfacial region. The proposed mBGn/CPC is a novel, promising cement formulation for the repair and regeneration of bone due to setting characteristics, physico-chemical and mechanical properties, and excellent <I>in vivo</I> tissue compatibility and bioactivity.</P>
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Mahapatra, Chinmaya,Singh, Rajendra K.,Kim, Jung-Ju,Patel, Kapil D.,Perez, Roman A.,Jang, Jun-Hyeog,Kim, Hae-Won American Chemical Society 2016 ACS APPLIED MATERIALS & INTERFACES Vol.8 No.41
<P>Providing an osteogenic stimulatory environment is a key strategy to construct stem cell-based bone-equivalent tissues. Here we design a stem cell delivering gel matrix made of collagen (Col) with bioactive glass nanocarriers (BGn) that incorporate osteogenic signaling molecule, fibroblast growth factor 18 (FGF18), a reservoir considered to cultivate and promote osteogenesis of mesenchymal stem cells (MSCs). The presence of BGn in the gel was shown to enhance the osteogenic differentiation of MSCs, possibly due to the therapeutic role of ions released. The mesoporous nature of BGn was effective in loading FGF18 at large quantity, and the FGF18 release from the BGn-Col gel matrix was highly sustainable with almost a zero-order kinetics, over 4 weeks as confirmed by the green fluorescence protein signal change. The released FGF18 was effective in accelerating osteogenesis (alkaline phosphatase activity and bone related gene expressions) and bone matrix formation (osteopontin, bone sialoprotein, and osteocalcin production) of MSCs. This was attributed to the bone morphogenetic protein (BMP) signaling pathway, where the FGF18 release stimulated the endogenous secretion of BMP2 and the downstream signal Smad1/5/8. Taken together, the FGF18-BGn/Col gel is considered an excellent osteopromoting depot to support and signal MSCs for bone tissue engineering.</P>
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Nanocements produced from mesoporous bioactive glass nanoparticles
Kang, Min Sil,Lee, Na-Hyun,Singh, Rajendra K.,Mandakhbayar, Nandin,Perez, Roman A.,Lee, Jung-Hwan,Kim, Hae-Won Elsevier 2018 Biomaterials Vol.162 No.-
<P><B>Abstract</B></P> <P>Biomedical cements are considered promising injectable materials for bone repair and regeneration. Calcium phosphate composition sized with tens of micrometers is currently one of the major powder forms. Here we report a unique cement form made from mesoporous bioactive glass nanoparticles (BGn). The nanopowder could harden in reaction with aqueous solution at powder-to-liquid ratios as low as 0.4–0.5 (<I>vs</I>. 2.0–3.0 for conventional calcium phosphate cement CPC). The cementation mechanism investigated from TEM, XRD, FT-IR, XPS, and NMR analyses was demonstrated to be the ionic (Si and Ca) dissolution and then reprecipitation to form Si-Ca-(P) based amorphous nano-islands that could network the particles. The nanopowder-derived nanocement exhibited high surface area (78.7 m<SUP>2</SUP>/g); approximately 9 times higher than conventional CPC. The immersion of nanocement in simulated body fluid produced apatite nanocrystallites with ultrafine size of 10 nm (<I>vs.</I> 55 nm in CPC). The ultrafine nanocement adsorbed protein molecules (particularly positive charged proteins) at substantial levels; approximately 160 times higher than CPC. The nanocement released Si and Ca ions continuously over the test period of 2 weeks; the Si release was unique in nanocement whereas the Ca release was in a similar range to that observed in CPC. The release of ions significantly stimulated the responses of cells studied (rMSCs and HUVECs). The viability and osteogenesis of rMSCs were significantly enhanced by the nanocement ionic extracts. Furthermore, the <I>in vitro</I> tubular networking of HUVECs was improved by the nanocement ionic extracts. The <I>in vivo</I> neo-blood vessel formation in CAM model was significantly higher by the nanocement implant when compared with the CPC counterpart, implying the Si ion release might play a significant role in pro-angiogenesis. Furthermore, the early bone forming response of the nanocement, based on the implantation in a rat calvarial bone defect, demonstrated a sign of osteoinductivity along with excellent osteocondution and bone matrix formation. Although more studies remain to confirm the potential of nanocement, some of the intriguing physico-chemical properties and the biological responses reported herein support the promise of the new ‘nanopowder-based nanocement’ for hard tissue repair and regeneration.</P>
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