Tunable layer-by-layer films containing hyaluronic acid and their interactions with CD44

Layer by layer (LbL) assembly is the hierarchical and controlled
association of oppositely charged polyelectrolytes (PEs). It is
usually applied to generate coatings or self-standing membranes
relevant for different technological fields.1,2 In the biomedical
area, biodegradable and biocompatible PEs have been used to
generate LbL-based drug delivery systems;3 substrates that induce
stem cell differentiation;4 surfaces promoting cell adhesion and
proliferation;2,5 and mimics of the extracellular matrix (ECM)6 and
the cancer microenvironment.5,7
One of the most studied LbL systems is built by the sequential
deposition of hyaluronic acid (HA) and poly-L-lysine (PLL)
(Fig. 1a).8–10 PLL is a common polycation used in LbL assembly
because of its biocompatibility and the fact that it is usually used
as a coating that promotes cell attachment.11,12 On the other hand,
HA is a negatively-charged, non-sulphated glycosaminoglycan that
is one of the main components of mammalian connective
tissue.13,14 HA is also an important multi-signalling molecule that
interacts with specific cell surface receptors/proteins (e.g. CD44)
and regulates different cellular functions.15,16 As an example, HA is
a key player in cancer cell biology and the acquisition of malignant
phenotypes.17 In fact, the tumour microenvironment is characterized
by excessive deposition of HA.18 Its molecular weight
(Mw) is also altered mostly due to the overexpression of hyaluronidases.
These changes affect the mechanical properties (usually
leading to a higher stiffness) and the biofunctionality of the matrix
of the cancerous tissues.19

Publication year: 2020
Authors: Amorim S.abc, Pashkuleva I. ab, Reis C. defg, Reis R.abc, Pires R. abc

a – 3B’s Research Group, I3Bs – Research Institute on Biomaterials, Biodegradables
and Biomimetics, University of Minho, Headquarters of the European Institute of
Excellence on Tissue Engineering and Regenerative Medicine, AvePark, Parque de
Ciencia e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Portugal.
b – ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimara˜es, Portugal
c – The Discoveries Centre for Regenerative and Precision Medicine, Headquarters at
University of Minho, Avepark, 4805-017 Barco, Guimara˜es, Portugal
d – i3S, University of Porto, Portugal
e – IPATIMUP, Porto, Portugal
f – Department of Pathology and Oncology, Faculty of Medicine, Porto University,
g – Institute of Biomedical Sciences Abel Salazar, University of Porto, Portugal

Published in: Journal of Materilals Chemistry, 2020, issue 17
DOI: 10.1039/d0tb00407c


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