Acknowledgements
6.2 Recent Advances of Smart Biomaterials
6.2.1 Smart Biomaterials that Mimic the Native Microenvironment
advances in various fields of biology have demonstrated that cells are highly sensitive to their environment. the native microenvironment consists of cells and the extracellular matrix (eCM). the mechanical, chemical and physical properties of the native microenvironment could affect the behavior of encap- sulated cells directly or indirectly. Mimicking the native microenvironment Table 6.1 Key parameters could be optimized for cell encapsulation technology.1
reprinted from Life Sciences, 143, M. hashemi and F. Kalalinia, appli- cation of encapsulation technology in stem cell therapy, 139–146, Copy- right (2015) with permission from elsevier.
Field of challenges parameters Materials science -purity
-Mechanical properties -toxicity and immunogenicity
-interactions with the encapsulated cells encapsulation technology -Formation of uniform capsules with excellent
repeatability and reproducibility -Stability of the cell capsules
-Chemical and physical properties of polymer Cell biology -the quality of the cells
-nutrition of the encapsulated cells -transplantation site of the cell capsules -Control of expansion, cultivation and
differentiation of stem cells
Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00144
has been widely exploited as an effective approach in tissue engineering. a suitable microenvironment could control cell morphology, cellular attach- ment and even promote cell differentiation. the properties of the eCM, architectures of cells and signaling pathways in living cells are key factors to be considered when mimicking the native environment.33–35
electrospun fibers have been identified for their use in numerous appli- cations,36 because of their large surface-to-volume ratio, controllable prop- erties, comparatively low cost and relatively high production rate. hydrogels are polymer networks that are extensively swollen in water and are highly similar to natural tissue.37 Consequently, they have also received consider- able attention over the last few decades. however, there are still several formi- dable problems when applying hydrogel materials, such as in mimicking the native microenvironment. Some researchers have found that a combination of electrospun fibers and hydrogels could overcome their respective intrin- sic defects, and take advantage of their individual superiority; particularly, it has been found that the complex fiber/gel architecture is similar to a native microenvironment. in Xu's review,38 they summarized approaches (Figure 6.1) that could be used to form various scaffolds with electrospun fibers and hydrogels, which could be applied in tissue engineering, drug delivery, and other biomedical fields. in the fiber/gel composite, the hydrogels are support- ing materials for the formation of a 3d structure to encapsulate cells and the
Figure 6.1 numerous strategies to integrate electrospun fibers with hydrogels.38 reproduced with permission from S. Xu, L. deng, J. Zhang, L. Yin and a. dong, J Biomed Mater Res B Appl Biomater, 2015, 104, 640. Copyright 2015: Wiley.
Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00144
embedded aligned electrospun fibers could guide the growth of individual cells. hsieh39 seeded neural stem/progenitor cells (nSpCs) in the composite of a physical hydrogel blend of ha and methylcellulose (haMC) and electro- spun fiber segments of poly(ε-caprolactone-co-d,l-lactide) (p(CL:dLLa)) or collagen with different culture media. their work demonstrated that a 3d microenvironment is very important to shape cell behavior, which is one of the critical factors for cell delivery applications.
Supramolecular biomaterials (Figure 6.2)40 are assembled through revers- ible, non-covalent interactions, and offer unprecedented application possi- bilities as drug carriers, and tissue engineering scaffolds. Supramolecular biomaterials could also be applied to engineer cell microenvironments.
Matthew highlighted the properties of supramolecular biomaterials compared with traditional biomaterials in terms of modularity, tunability, responsive- ness and biomimicry.40 the reversibility of supramolecular interactions has been applied to the technologies of preparing bioactive matrices from peptides or engineered proteins to control cell behavior41–44 and support therapeutic cells.45,46 in addition, materials designed with supramolecular principles could direct cell differentiation and guide cell phenotype. gabriel reported self-assembled scaffolds consisting of supramolecular peptide nanofibers that direct the differentiation of neural progenitor cells into neurons.47 a monodomain gel composed of massively aligned bundles of nanofibers was used as a platform to facilitate the differentiation and aligned growth of neural cells.48
designing hydrogels with biomolecules present to promote specific cell–
substrate interactions is another way to mimic a cell's microenvironment.
Figure 6.2 Special properties of supramolecular biomaterials.40 reproduced with permission from Macmillan publishers Ltd: M. J. Webber, e. a. appel, e.
W. Meijer and r. Langer, Nature Materials, 2015, 15, 13. Copyright 2015:
nature publishing group.
Published on 03 May 2017 on http://pubs.rsc.org | doi:10.1039/9781788010542-00144
Chemical signals, mechanical cues, and physical cues play key roles in cell–
eCM interactions. Firstly, growth factors are key components present within the eCM that dictate cell fate. the site-targeted combination of growth factors and hydrogels has been applied to promote cell development in vitro.
Fibroblast growth factor 1 (FgF-1) and bone morphogenetic protein 4 (BMp-4) are two pro-adipogenic soluble factors present in eCM. Midori49 encapsu- lated these two factors in alginate microgels, with the dual-stage delivery of FgF-1 and BMp-4 to induce adipogenesis. the development of mature adipo- cytes was promoted in this 3d, dual-stage delivery system. Secondly, cell fate could be influenced by the mechanical properties of an effective biomimetic hydrogel. Sur showed that dissociated hippocampal cells cultured on a softer peptide amphiphile hydrogel could significantly increase their differenti- ation and maturation.50 thirdly, biomaterials' size and shape are physical cues that affect cell microenvironments. Certain research has demonstrated that the behaviors of many cells can be modified by fibers of sub-micron dimension.51