Scaffold technologies for controlling cell behavior in tissue engineering

Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
Biomedical Materials (Impact Factor: 3.7). 01/2013; 8(1):010201. DOI: 10.1088/1748-6041/8/1/010201
Source: PubMed


Scientists in the field of tissue engineering are now applying the principles of cell biology, material science and biomedical engineering to create biological substitutes that will restore and maintain normal function in diseased and injured tissues/organs [1-3]. Tissue-engineered scaffolds should (i) facilitate the localization and delivery of tissue-specific cells to precise sites in the body, (ii) maintain a three-dimensional architecture that permits the formation of new tissues, and (iii) guide the development of new tissues with appropriate function. Moreover, it has been demonstrated that tissue morphogenesis is heavily influenced by the interactions between cells and the extracellular matrix (ECM) during normal tissue development. While simple polymeric scaffolds that have been used in the past provide architectural support for neo-tissue development, they do not adequately mimic the complex interactions between tissue-specific cells and the tissue-specific ECMs that promote functional tissue regeneration. Thus, future advances in tissue engineering will depend on the development of novel scaffolding systems that actively modulate cell behaviors for functional tissue regeneration. In this regard, the present special issue describes the current status of scaffold technologies in tissue engineering and regenerative medicine applications. This special issue includes a range of review and original articles related to various scaffolding technologies in tissue engineering. Oh and Lee review hydrophilization of synthetic biodegradable polymeric scaffolds for improving cell/tissue compatibility [4]. This technique has been considered as a simple and effective approach to achieve desirable in vitro cell culture and in vivo tissue regeneration within the synthetic polymeric scaffolds. Today, electrospinning has been widely used as a fabrication method to generate nanofibers with a diameter range of several micrometers to 100 nm or less for various tissue applications. Although many other scaffold fabrication technologies are used in tissue engineering applications, few provide scaffolds with the critical similarities to natural ECM, which electrospinning of nanofibers can provide. Electrospinning has become a popular alternative fabrication method during the previous two decades, as it can be applied to many disciplines and is a relatively simple and inexpensive scaffold fabrication process. Shin and colleagues review the current approaches to the development of electrospun nanofibers as a scaffold for tissue engineering application [5]. These electrospun scaffolds can also be functionalized by adding biochemical and mechanical cues to enhance cellular interactions for tissue engineering applications. Levorson et al describe their work with fabrication and characterization of multi-scale electrospun scaffolds for cartilage regeneration [6]. These scaffolds were able to maintain scaffold cellularity in serum-free conditions as well as aid the deposition of glycosaminoglycans. Xu et al present a novel controllable dual protein delivery system through electrospun fibrous scaffolds with different hydrophilicities [7]. Hydrogels can be used in injectable approaches to cell therapy and tissue engineering, which offers several advantages. This approach can replace multiple surgeries with minimally invasive injection procedures. However, the hydrogel-based biomaterials used in these studies have been limited by low-dimensional stability and limited nutrient and oxygen supply. To overcome these problems, Lee and colleagues developed injectable alginate particle-embedded fibrin hydrogels for soft tissue reconstruction [8]. They demonstrate that fibrin may enhance cell proliferation and accelerate the formation of ECM proteins in the alginate-fibrin system, while the alginate particles could contribute to volume retention. This injectable hybrid system composed of degradable and non-degradable hydrogels may be a preferred approach to repair soft tissue defects. In the absence of methods for de novo construction of a true ECM mimic from purified components, such as collagen and elastin, decellularized tissue matrices are currently considered an ideal scaffolding system due to their structural and mechanical similarity to native tissues and because they contain tissue-specific ECM proteins which remain after decellularization. Yoo and colleagues review decellularization techniques and possible methods for using these decellularized matrices for whole organ engineering [9]. Kim et al developed a composite scaffold which is composed of collagen matrix derived from decellularized porcine bladder submucosal matrix and synthetic poly(lactide-co-glycolide) polymer [10]. This composite scaffold provides a microenvironment that can facilitate osteogenic differentiation of amniotic fluid-derived stem cells. Also, Choi et al investigated the interactions between the ECM environment and human corneal endothelial cells to improve cell proliferation and function [11]. Lastly, biomedical imaging supports the development of enabling technologies including real-time, non-invasive tools for assessing the function of engineered tissues and real-time assays that monitor the interaction of cells and their environment at the molecular and organelle level. For instance, implanted scaffolds eventually degrade and are replaced by cells generating an essentially normal tissue over time. Thus, the rate of scaffold degradation and ECM production by cells must be equivalent for successful outcomes. In order to avoid these pitfalls, non-invasive optical imaging is currently being investigated for real-time monitoring of in situ degradation of implanted scaffolds, as well as that of cellular behaviors, using a combination of nanoparticles and tissue-engineered scaffolds. Owens et al developed highly charged cyanine fluorophores for trafficking scaffold degradation [12], and they continually developed near-infrared lipophilic fluorophores for tracing tissue growth [13]. These approaches will play a key role in monitoring the fate of implanted scaffolds and cells in the body, which will be helpful in translating tissue engineering strategies to the clinic. Reference [1] Atala A 2006 Recent developments in tissue engineering and regenerative medicine Curr. Opin. Pediatr. 18 167-71 [2] Atala A 2009 Engineering organs Curr. Opin. Biotechnol. 20 575-92 [3] Orlando G, Wood K J, Stratta R J, Yoo J J, Atala A and Soker S 2011 Regenerative medicine and organ transplantation: past, present, and future Transplantation 91 1310-7 [4] Oh S H and Lee J H 2013 Hydrophilization of synthetic biodegradable polymer scaffolds for improved cell/tissue compatibility Biomed. Mater. 8 014101 [5] Rim N G, Shin C S and Shin H 2013 Current approaches to electrospun nanofibers for tissue engineering Biomed. Mater. 8 014102 [6] Levorson E J, Sreerekha P R, Chennazhi K P, Kasper F K, Nair S V and Mikos A G 2013 Fabrication and characterization of multiscale electrospun scaffolds for cartilage regeneration Biomed. Mater. 8 014103 [7] Xu W, Atala A, Yoo J J and Lee S J 2013 Controllable dual protein delivery through electrospun fibrous scaffolds with different hydrophilicities Biomed. Mater. 8 014104 [8] Hwang C M, Ay B, Kaplan D L, Rubin J P, Marra K G, Atala A, Yoo J J and Lee S J 2013 Assessments of injectable alginate particle-embedded fibrin hydrogels for soft tissue reconstruction Biomed. Mater. 8 014105 [9] Arenas-Herrera J E, Ko I K, Atala A and Yoo J J 2013 Decellularization for whole organ bioengineering Biomed. Mater. 8 014106 [10] Kim J, Jeong S Y, Ju Y M, Yoo J J, Smith T L, Khang G, Lee S J and Atala A 2013 In vitro osteogenic differentiation of human amniotic fluid-derived stem cells on a poly(lactideco- glycolide) (PLGA)-bladder submucosa matrix (BSM) composite scaffold for bone tissue engineering Biomed. Mater. 8 014107 [11] Choi J S, Kim E Y, Kim M J, Giegengack M, Khang F A, Khang G and Shay S 2013 In vitro evaluation of the interactions between human corneal endothelial cells and extracellular matrix proteins Biomed. Mater. 8 014108 [12] Owens E A et al 2013 Highly charged cyanine fluorophores for trafficking scaffold degradation Biomed. Mater. 8 014109 [13] Kim S H, Park G, Hyun H, Lee J H, Ashitate Y, Choi J, Hong G H, Owens E A, Henary M and Choi H S 2013 Near-infrared lipophilic fluorophores for tracing tissue growth Biomed. Mater. 8 014110.

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    • "To achieve functional tissue regeneration, novel scaffold systems that combine the structural function of the scaffold and ECM components to regulate cell behaviour are being developed (Lee and Atala, 2013). Further approaches concentrate on the introduction of reactive groups that may support cell adhesion or the direct immobilization of growth factors, with a sustained release in vitro and in vivo (Lee et al., 2012; Reyes et al., 2012). "
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    ABSTRACT: Surface modification of materials designed for regenerative medicine may improve biocompatibility and functionality. The application of glycosaminoglycans (GAGs) and chemically sulphated GAG derivatives is a promising approach for designing functional biomaterials, since GAGs interact with cell-derived growth factors and have been shown to support fibroblast growth in two-dimensional (2D) cultures. Here, coatings with artificial extracellular matrix (aECM), consisting of the structural protein collagen I and the GAG hyaluronan (HA) or sulphated HA derivatives, were investigated for their applicability in a three-dimensional (3D) system. As a model, macroporous poly(lactic-co-glycolic acid) (PLGA) scaffolds were homogeneously coated with aECM. The resulting scaffolds were characterized by compressive moduli of 0.9-1.2 MPa and pore sizes of 40-420 µm. Human dermal fibroblasts (dFbs) colonized these aECM-coated PLGA scaffolds to a depth of 400 µm within 14 days. In aECM-coated scaffolds, collagen I(α1) and collagen III(α1) mRNA expression was reduced, while matrix metalloproteinase-1 (MMP-1) mRNA expression was increased within 7 days, suggesting matrix-degradation processes. Stimulation with TGFβ1 generally increased cell density and collagen synthesis, demonstrating the efficiency of bioactive molecules in this 3D model. Thus, aECM with sulphated HA may modulate the effectivity of TGFβ1-induced collagen I(α1) expression, as demonstrated previously in 2D systems. Overall, the tested aECM with modified HA is also a suitable material for fibroblast growth under 3D conditions. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
    No preview · Article · May 2015 · Journal of Tissue Engineering and Regenerative Medicine
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    • "Biologically-derived materials, such as alginate and agarose have been traditionally used for scaffolds construction but they may induce inflammation or fibrotic overgrowth which can impede nutrient and oxygen transport. According to Lee et al. 2013 (57) tissue-engineered scaffolds should (I) facilitate the delivery of tissuespecific cells to precise sites in the body, (II) maintain a 3D architecture that permits the formation of new tissues, (III) guide the development of new tissues with appropriate function and (IV) be reabsorbed by the cells (57). Hydrogels are a highly attractive material used as syn- Ferro F et al. 5 Razavi Int J Med. 2014;(2):e17803 thetic ECM substitutes due to their ability to mimic the hydrophilic nature of most tissues, investigate cell physiology , and fabricate tissues outside the organism. "
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    ABSTRACT: Context: Early development of many organs shows many morphological and molecular similarities (teeth, lung, hair, kidney and etc.). Fundamental questions in organogenesis are related to the identification of a simplified model which is able to mimic the molecular mechanisms involved in pattern organization and cell fate determination as well. Evidence Acquisition: It is widely accepted that cells behave more natively if cultured in three-dimensional conditions. Advances in 3D non-destructive, non-invasive analysis methods and improvements in the multi-scale techniques and bioreactors to obtain test and culture 3D cell aggregates have been made. On the other hand, even if 3D aggregate culture methods are able to recapitulate in vitro the cell-extracellular matrix interactions properly observed in vivo, and the synthetic/natural matrix and scaffolds have biochemical and mechanical properties, in order to mimic the native extracellular matrix, both of these systems possesses some limitations and some methodological improvements are needed. Results: The processes by which re-aggregated adult single cell types or adult and embryonic explanted tissues are able to recapitulate embryogenesis in vitro, when cultured in adhesion or embedded in 3D gels, is not surprising and is clearly under the control of a reminiscent cellular memory which recapitulates early developmental stages. Conclusions: Our underlying hypothesis is that recapitulating the three-dimensional early embryonic structure, in order to reproduce
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