Biomaterial can serve as a regeneration promoting matrix


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Biomaterials constitute a remarkable option for “transplantation medicine”-approaches with regards to chronic spinal cord injury (SCI), after a defect (“cyst”) has been formed caused by tissue loss at the lesion site. Early concepts of rigid prosthesis, which remain at the SCI lesion, are limited due to the need of surgical implantation and the associated, additional damage of precious, healthy tissue. Furthermore, a persistent prosthesis will cause an encapsulating (gliotic) tissue response impairing its integration. Lastly, given that the spinal cord is versatile and flexible depending on the position of the spine, a rigid neuroprosthesis implanted in “softer” spinal cord will cause additional harm with each movement of the spinal cord – squeezing and damaging adjacent healthy tissue.

Funded by the Wings for Life foundation, the group led by Prof. Michael Sofroniew (UCLA) took up the challenge to overcome the caveats mentioned above and developed an injectable (very limited additional injury) and absorbable (no permanent “foreign body” in the spinal cord) neuroprosthetic approach, which offers a transient matrix to facilitate nerve regeneration. Prof. Sofroniew tested the new type of biomaterial in-vivo by injections into the brain. The results from this proof of principle experiments pave the way for the application in the spinal cord after chronic SCI.

The injury of the spinal cord has multiple impacts on the tissue as it mechanically breaks the long axons that support movement and sensation but also destroys the tissue “matrix” resulting in a liquid filled cavity (cyst), empty of any cell type and surrounded by a so-called glial scar. This cyst is both a physical and chemical barrier to the axonal regeneration and the subsequent remyelination needed to restore proper functions after the injury. The development of biomaterials that can bridge this barrier is one of the challenges in the therapeutic approaches for chronic spinal cord injury.

Another challenge comes from the fact that some molecules that proved to have any kind of beneficial effect are not able to cross the blood-brain barrier, which normally protects the brain from external pathogens. Biomaterials that can provide sustained and site specific delivery of such compounds in the CNS have a great potential for therapeutic applications.

The work of Prof. Sofroniew led to the development of a new type of biomaterial called DCH that can bridge the injury site while delivering any additional therapeutical molecule of interest.  This biomaterial has the advantage of being liquid when it is injected in the injury site allowing an optimal integration within the cavity without causing additional mechanical damage. The liquid then polymerizes into a semi-solid gel that can bridge the injury site and sustain cellular regrowth. Another advantage of this innovative compound is that additional molecules can be added in the liquid which will result in sustained delivery (behind the blood-brain barrier) of any kind of treatment aiming at restoring the functional deficit (neuroprotection, axonal regrowth, remyelination, etc). Prof. Sofroniew describes the proof of principle that DHC can be safely injected in the CNS and form a depot for bioactive proteins that can be released over a distance of several millimeters and over a time of about 4 weeks.

Reference:
Sustained local delivery of bioactive nerve growth factor in the central nervous system via tunable diblock copolypeptide hydrogel depots. Song B, Song J, Zhang S, Anderson MA, Ao Y, Yang CY, Deming TJ, Sofroniew MV. Biomaterials. 2012 Dec; 33(35): 9105-16. Epub 2012 Sep 15.