The challenge
Peripheral nerve injuries (PNI) are commonly caused by trauma to upper and lower limbs; they deeply impact the quality of life of patients and may be responsible for significant socio-economic burdens.
Presently, these injuries are treated by transplanting nerves from a different part of the patient's body to the injury site (autografting), but this method causes donor site loss of sensitivity and morbidity; it continues to result in disappointing outcomes in regards to regeneration and suboptimal motor-sensory functionality.
The solution
Senior Clinical Lecturer at The University of Manchester and Consultant Plastic and Reconstructive Surgeon at University Hospital of South Manchester, Dr Adam Reid, and his team are developing completely bioengineered nerve grafts that exploit regenerative approaches.
The science
Regenerative approaches necessitate growing the cells involved in nerve repair in vitro prior to implantation into the patient. Schwann cells (SCs) are the key cells involved in nerve regeneration but obtaining enough SCS entails harvesting nerves belonging to healthy patients.
Another method is to harvest and expand human derived-adipose stem cells (hdASC) easily obtainable from fat tissues, and chemically differentiate them in vitro towards the Schwann-like phenotype. In order to achieve this, new, translatable biomaterials are needed. In this study, a comparison of synthetic PeptiGels® and animal-derived collagen 1 is made, in order to discover if hydrogel scaffolds such as these will enhance the outcome of hdASCs in this process.
We have demonstrated that PeptiGels® can be used as scaffolds for the culture and differentiation of hdASCs in vitro towards a Schwann cell-like phenotype. We are continuing to explore the potential of PeptiGels® to generate fully-synthetic bioengineered nerve grafts for the treatment of PNls.
Dr Adam Reid, Senior Clinical Lecturer in Plastic and Reconstructive Surgery, The University of Manchester
The results
PeptiGels®, Alpha1 and Alpha2, were successful in enabling culture of hdASCs with decent viability and proliferation over four days. Gene expression analysis of key differentiation markers showed that PeptiGeIs® aided the differentiation of hdACSs toward a Schwann-like phenotype which was preserved when the chemical simulation was removed. PeptiGel® Alpha2 was employed successfully for the long-term culture (20 days) of hdASCs displaying greater stability in comparison with collagen 1.
Image Credit: Manchester BIOGEL
Additionally, both Peptigels® Alpha1 and Alpha2 illustrated their value for the culture of rat dorsal root ganglia (DRG) neurons, displaying decent cell attachment and functional neurite sprouting, even where there is no laminin coating.
The future
PeptiGel® Alpha2 has shown itself proficient in delivering cells for the regeneration of peripheral nerves. Utilizing PeptiGel Alpha2 for the bioengineering of nerve grafts in small animal trials is the next step.
About Manchester BIOGEL
Over 15 years ago, Professors Aline Miller and Alberto Saiani at The University of Manchester synthesised a self-assembling oligo-peptide with interesting gelation properties. This work started with a small grant from the University.
Over subsequent years, the team meticulously crafted and studied self-assembling peptides to perfect their platform technology and produce a range of hydrogels ideal for 3D cell culture. In 2014, due to a demand for their materials, our company, Manchester BIOGEL was founded to enable these hydrogels to be readily available to researchers wishing to create new opportunities in the high-growth fields of 3D cell culture, 3D bioprinting and medical devices. Since opening our doors, we have supported scientists in the UK and beyond to create optimal environments for a wide variety of cell types.
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