Scaffold technologies for controlling cell behavior in tissue engineering

Abstract

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 restoreand maintain normal function in diseased and injured tissues/organs [1–3]. Tissue-engineeredscaffolds should (i) facilitate the localization and delivery of tissue-specific cells to precisesites in the body, (ii) maintain a three-dimensional architecture that permits the formation ofnew tissues, and (iii) guide the development of new tissues with appropriate function.Moreover, it has been demonstrated that tissue morphogenesis is heavily influenced by theinteractions between cells and the extracellular matrix (ECM) during normal tissuedevelopment. While simple polymeric scaffolds that have been used in the past providearchitectural support for neo-tissue development, they do not adequately mimic the complexinteractions between tissue-specific cells and the tissue-specific ECMs that promotefunctional tissue regeneration. Thus, future advances in tissue engineering will depend on thedevelopment of novel scaffolding systems that actively modulate cell behaviors forfunctional tissue regeneration. In this regard, the present special issue describes the currentstatus of scaffold technologies in tissue engineering and regenerative medicine applications.This special issue includes a range of review and original articles related to variousscaffolding technologies in tissue engineering. Oh and Lee review hydrophilization ofsynthetic biodegradable polymeric scaffolds for improving cell/tissue compatibility [4]. Thistechnique has been considered as a simple and effective approach to achieve desirablein 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 nanofiberswith a diameter range of several micrometers to 100 nm or less for various tissueapplications. Although many other scaffold fabrication technologies are used in tissueengineering applications, few provide scaffolds with the critical similarities to natural ECM,which electrospinning of nanofibers can provide. Electrospinning has become a popularalternative fabrication method during the previous two decades, as it can be applied to manydisciplines and is a relatively simple and inexpensive scaffold fabrication process. Shin andcolleagues review the current approaches to the development of electrospun nanofibers as ascaffold for tissue engineering application [5]. These electrospun scaffolds can also befunctionalized by adding biochemical and mechanical cues to enhance cellular interactionsfor tissue engineering applications. Levorson et al describe their work with fabrication andcharacterization of multi-scale electrospun scaffolds for cartilage regeneration [6]. Thesescaffolds were able to maintain scaffold cellularity in serum-free conditions as well as aid thedeposition of glycosaminoglycans. Xu et al present a novel controllable dual protein deliverysystem 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 withminimally invasive injection procedures. However, the hydrogel-based biomaterials used inthese studies have been limited by low-dimensional stability and limited nutrient and oxygensupply. To overcome these problems, Lee and colleagues developed injectable alginateparticle-embedded fibrin hydrogels for soft tissue reconstruction [8]. They demonstrate thatfibrin may enhance cell proliferation and accelerate the formation of ECM proteins in thealginate–fibrin system, while the alginate particles could contribute to volume retention. Thisinjectable hybrid system composed of degradable and non-degradable hydrogels may be apreferred approach to repair soft tissue defects.In the absence of methods for de novo construction of a true ECM mimic from purifiedcomponents, 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 afterdecellularization. Yoo and colleagues review decellularization techniques and possiblemethods for using these decellularized matrices for whole organ engineering [9]. Kim et aldeveloped a composite scaffold which is composed of collagen matrix derived fromdecellularized porcine bladder submucosal matrix and synthetic poly(lactide-co-glycolide)polymer [10]. This composite scaffold provides a microenvironment that can facilitateosteogenic differentiation of amniotic fluid-derived stem cells. Also, Choi et al investigatedthe interactions between the ECM environment and human corneal endothelial cells toimprove cell proliferation and function [11].Lastly, biomedical imaging supports the development of enabling technologies includingreal-time, non-invasive tools for assessing the function of engineered tissues and real-timeassays that monitor the interaction of cells and their environment at the molecular andorganelle level. For instance, implanted scaffolds eventually degrade and are replaced bycells generating an essentially normal tissue over time. Thus, the rate of scaffold degradationand ECM production by cells must be equivalent for successful outcomes. In order to avoidthese pitfalls, non-invasive optical imaging is currently being investigated for real-timemonitoring 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 developedhighly charged cyanine fluorophores for trafficking scaffold degradation [12], and theycontinually 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 cellsin 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 andorgan transplantation: past, present, and future Transplantation 91 1310–7[4] Oh S H and Lee J H 2013 Hydrophilization of synthetic biodegradable polymer scaffolds forimproved cell/tissue compatibility Biomed. Mater. 8 014101[5] Rim N G, Shin C S and Shin H 2013 Current approaches to electrospun nanofibers for tissueengineering Biomed. Mater. 8 014102[6] Levorson E J, Sreerekha P R, Chennazhi K P, Kasper F K, Nair S V and Mikos A G 2013Fabrication 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 electrospunfibrous 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 2013Assessments of injectable alginate particle-embedded fibrin hydrogels for soft tissuereconstruction Biomed. Mater. 8 014105[9] Arenas-Herrera J E, Ko I K, Atala A and Yoo J J 2013 Decellularization for whole organbioengineering 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 vitroosteogenic differentiation of human amniotic fluid-derived stem cells on a poly(lactideco-glycolide) (PLGA)–bladder submucosa matrix (BSM) composite scaffold for bone tissueengineering 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 vitroevaluation of the interactions between human corneal endothelial cells and extracellular matrixproteins 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 Mand Choi H S 2013 Near-infrared lipophilic fluorophores for tracing tissue growth Biomed. Mater. 8 014110