Munira Shahbuddin
May
2017
May the force be with
you
Ubiquitous force – that
impact cellular functions and regeneration.
Understanding
the role of controlled degradation and mechanotransduction
(the minute force that capable of influencing cellular behaviour and functions)
examining the current thinking and directions of tissue engineering.
In this
premise, my writing will reflect i) the current understanding of development of
DRT designs and experimental rationale and techniques in vivo and in vitro, and
ii) recent efforts to consider incorporation of exogenous cues (cells, growth
factors) in the DRT for complete) organ regeneration (with adnexa).
The ultimate
goal of the treatment of cutaneous burns and wounds is to restore, repair and
regenerate damaged skin structurally and functionally into its original state.
Yannas et al. works over the past 40 years have shown great potential and
success of collagen based Dermal and Nerve Regenerative Template in improving
the rate and quality of the injured site with regeneration of skin, nerve and
their appendages.
The work
proposed that controlled degradation rate and porosity of the hydrogel
scaffolds between 40 and 120 um are the key to scarless wound healing. The
basis that optimized pore size can regulate tissue remodelling and development
of skin and nerve came from larger surface area enable the cells to adhere and
spread onto the surface, while at the same time reducing the contraction
between each cell. Controlled degradation give enough time for the cells to
mature, differentiate and produce fibrous, collagenous tissues for skin
remodelling and regeneration.
It is
essential to note that DRT promotes skin regeneration without the implantation
of exogenous cells – but recruitment of cells from the surroundings. In case
for 3rd degree burn where most part of the skin are damaged and lack
of biochemical cues for renewal and restoration – is stem cells implantation be
the ultimate approach compared to skin grafting from auto, allo and xeno
sources.
One of the
most interesting topics in the book lingers on the subject of spontaneous and
induced regeneration in adult organs. Like other mammals, human has the ability
to heal but often the newly synthesized materials (or organ) (or adnexa) are
often overlapped with the existing architecture, creating dent and un-uniform
structure – called scar.
It is
important to address the capabilities and limitations of DRT (in the present)
to design/improve new materials for organ regeneration.
Intelligent Biomaterials
Should the
new so called biomimetic materials be complex and incorporate
multi-functionality for tissue engineering applications?
Addressing Material-ECM interactions
– mechanotransduction.
Mechanical
properties of scaffolds are critical to the regulation of cellular functions and
behaviour in organ regeneration.
Cells derive
a vast wealth of information from their environment. The native extra-cellular
matrix (ECM) surrounded, and produced, by cells is instructive, providing a
dynamic and spatially heterogeneous constellation of microstructural,
compositional and mechanical cues that can influence cell behavior.
Harnessing
the mechanosensitive capacity of cells, in particular, provides immense
opportunities. The mechanical properties of tissues, biomaterials, cells, and
biomolecules have profound biological consequences in terms of implant
bioactivity versus failure, transmission of mechanical stimuli, and for a wide
range of processes at the tissue, cell and subcellular levels. The key roles in
molecular signaling pathways are played by cell adhesion complexes and
cytoskeleton, whose contractile forces are transmitted through intra and trans
cellular domains.
Scaffolds for tissue engineering: current
thinking and future directions
The ultimate
goal of tissue engineering is to replicate the exact nature of organs,
pathophysiologically. There are many state of the art research in progress to
engineer in vitro, in vivo and ex vivo every tissue and organ in the body including the use of 3D
printer, decellularization of animal organs, construction of organs from
natural and synthetic polymeric materials and genetic editing: removal of
animals’ protein allelles and genetic loci.
Lack of
vascularity in scaffolds and tissue engineered constructs is a major challenge,
and improving vascularization strategies is considered one of the areas
requiring the most extensive research in the field of tissue engineering.
One way to
improve vascularization might to be engineer microvasculature by cells in the
scaffolds prior to implantation.
However, the efficacy of in vitro and in vivo tissue engineering using patients' own cell will require least two procedures of harvesting and cell culture in
laboratory is an issue as the procedure will take at least three to four weeks before transplantation. Therefore we need new techniques and scientific knowledge for the future design on materials for organ restoration and regeneration. Although I am very skeptical on the use of animal organs for transplantation due to the danger of disease and viral transmissions, new procedures and research are welcome. My fear to this technology should not halt the progress of scientific exploration but rather promoting ethical and responsible value in research.
