Biomedical Engineering Reference
In-Depth Information
Keywords Hydrogels · Stem cells · Drug delivery · Tissue regeneration ·
Biomedical
1 Introduction
Stem cells represent an ideal cell source for applications in tissue engineering and
regenerative medicine due to their ability to proliferate and differentiate to a wide
variety of lineages for use in cellular therapies [ 1 , 2 ]. Over the last decade, several
advances have been made in isolation, expansion and differentiation of a variety
of stem cell types. Immense efforts are ongoing to decipher the components of
the 'stem cell niche' and the molecular mechanisms that regulate the self-renewal,
proliferation, differentiation and migration of stem cells to become committed
somatic cell types [ 3 ]. Undoubtedly, determining the specific niche components
and deciphering the underlying mechanisms will allow researchers to better under-
stand stem cell behavior and to unravel the full therapeutic potential of stem cells.
When applying stem cells for tissue regeneration, it is becoming increasingly
important to also consider the dynamic complexity of the tissue environment,
either in healthy or diseased state, and how these may affect the stem cell fate and
functions. The level of oxygenation, oxidative stress, inflammation, complexity of
cell populations and signaling events present in the site of tissue injury are likely
to influence the stem cell engraftment and survival.
Recent advances in the field of biomaterials have provided synthetic three-
dimensional (3-D) extracellular matrices (ECM) with appropriate biophysical and
biochemical signalling cues to probe changes in stem cell behaviours and func-
tions. For instance, it is now becoming possible to study the changes in stem cell
behaviour in a well-controlled microenvironment. Specific ECM components and
morphogenetic factors may be introduced into the microenvironment to influ-
ence the stem cell fate and functions. Additional tissue elements such as hypoxia,
oxidative stress and even inflammation may also be added to the microenviron-
ment to interrogate the stem cell responses to these elements when they are being
introduced into the tissue site of injury. Understanding the complex interactions of
stem cells and the extracellular microenvironment would therefore provide impor-
tant information for the design and engineering of the next-generation biomaterials
for delivery of stem cells to the tissue site of injury.
Among the biomaterials, hydrogels are most commonly used as scaffolds and
substrates for stem cell culture and as carrier systems for delivery of stem cells
because of their tunable tissue-like properties, controllability of degradation and
release behavior, and adaptability in a clinical setting for minimally invasive sur-
gical procedures. Hydrogels may be made from natural and synthetic polymers.
These highly-hydrated networks can be held together via physical or chemical
crosslinks, can be made biodegradable, and responsive to specific stimuli such as
pH and temperature, and can be engineered to deliver therapeutic stem cells and
soluble factors in a sustained and controlled fashion.
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