Wound care
“The underlying reason why chronic wounds are difficult to treat is that they tend to be stuck in a prolonged state of inflammation, which can affect the ability of the skin cells to respond to signals that instruct tissue repair,” explains Alan Smith, professor of biopolymer science at the University of Huddersfield. “Skin grafts are the current gold standard for chronic wound repair. However, excessive pain and morbidity of the donor site are significant side effects when using skin grafts.” He adds that the donor site is often not thick enough to be used in some wounds, as there can be significant areas of tissue damage. On top of that, donor tissue is limited, and it can be difficult to harvest more if the graft does not take, leaving the patient with few options.
New skin technology's potential The good news is that these problems may soon be overcome. Thanks to a growing wave of advanced therapies, involving bioengineered artificial skin substitutes, it may one day be possible to generate new skin for patients while sidestepping the limitations associated with skin grafts. Together with researchers from the University of Huddersfield and Birmingham, Smith has been working on precisely such a technology. His team have designed a 3D-printed substitute that simulates the different cell types found in actual skin. “Although a number of skin replacements exist, so far it has not been possible to replicate the compositional, mechanical and cellular structure of human skin,” says Smith. “Our research uses a specialised 3D printing technique to produce a cell containing tri-layered structure. It has biological and mechanical properties that are similar to native skin across the three layers – epidermis, dermis and hypodermis.” To date, most skin substitutes have been designed using a biological or materials science approach. Biological approaches use cells to build skin-like constructs, but these constructs often are not thick enough and fail to replicate the complexity of true skin structure.
The approach of materials science, by contrast, can achieve the desired mechanical behaviours. However, because it uses materials like hydrogels and polymers, it generally lacks the biological stimulus required to help regenerate the tissue. Smith’s team have bridged the gap between these two approaches by using a low-viscosity bioink containing cells suspended in a scaffold material. They have also developed a technique called suspended layer additive manufacture (SLAM) to ensure the material solidifies properly. “Using the suspending medium allows the liquid bioink to be deposited and remain in the liquid state until the printing is complete without changing
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shape,” says Smith. “The printed liquid can then be solidified accordingly once printing is complete. We can create regional variations in physical, chemical and biological properties within a single construct that are more akin to native skin.” The technique in question could feasibly be carried out in the clinic – especially as 3D bioprinting technologies progress and more personalised treatments become the norm.
An example of a skin substitute for partial thickness wounds (model by Mallinckrodt). Though effective, these types of subsitutes are not as useful for treating full thickness wounds.
“Our research uses a specialised 3D printing technique to produce a cell containing tri-layered structure.” Professor Alan Smith
“As no two wounds are the same, being able to fabricate an exact match using a patient’s own cells to enhance the regeneration of the skin, in a manner that cannot currently be achieved using a one-size-fits-all approach to wound care, is an exciting proposition,” says Smith.
Of course, that ambition is some way afield for
now. While the technique achieved impressive results on excised pig skin, the researchers have not yet tested the model on chronic wounds. They hope to show that it is effective on an animal chronic wound model before moving the technology forward towards human clinical trials. Across the Atlantic, at McGill University in Quebec, researchers have been working on a new injectable hydrogel for wound repair. This material might one day be used not only for treating chronic wounds, but also for repairing organs such as the heart, muscles and vocal chords.
“Many injectable biomaterials, mostly hydrogels, have been developed for tissue repair over the last
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Mallinckrodt
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