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Item type:Publication, Access status: with files , Low-pressure micro-mechanical re-adaptation device sustainably and effectively improves locomotor recovery from complete spinal cord injury(Springer, 2018-11-26); ; ; ; Traumatic spinal cord injuries result in impairment or even complete loss of motor, sensory and autonomic functions. Recovery after complete spinal cord injury is very limited even in animal models receiving elaborate combinatorial treatments. Recently, we described an implantable microsystem (microconnector) for low-pressure re-adaption of severed spinal stumps in rat. Here we investigate the long-term structural and functional outcome following microconnector implantation after complete spinal cord transection. Re-adaptation of spinal stumps supports formation of a tissue bridge, glial and vascular cell invasion, motor axon regeneration and myelination, resulting in partial recovery of motor-evoked potentials and a thus far unmet improvement of locomotor behaviour. The recovery lasts for at least 5 months. Despite a late partial decline, motor recovery remains significantly superior to controls. Our findings demonstrate that microsystem technology can foster long-lasting functional improvement after complete spinal injury, providing a new and effective tool for combinatorial therapies.Publicationtype: Journal ArticleScopus© Citations 3 314 317 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Experimental strategies to bridge large tissue gaps in the injured spinal cord after acute and chronic lesion(2016-04-05); ; ; ; After a spinal cord injury (SCI) a scar forms in the lesion core which hinders axonal regeneration. Bridging the site of injury after an insult to the spinal cord, tumor resections, or tissue defects resulting from traumatic accidents can aid in facilitating general tissue repair as well as regenerative growth of nerve fibers into and beyond the affected area. Two experimental treatment strategies are presented: (1) implantation of a novel microconnector device into an acutely and completely transected thoracic rat spinal cord to readapt severed spinal cord tissue stumps, and (2) polyethylene glycol filling of the SCI site in chronically lesioned rats after scar resection. The chronic spinal cord lesion in this model is a complete spinal cord transection which was inflicted 5 weeks before treatment. Both methods have recently achieved very promising outcomes and promoted axonal regrowth, beneficial cellular invasion and functional improvements in rodent models of spinal cord injury. The mechanical microconnector system (mMS) is a multi-channel system composed of polymethylmethacrylate (PMMA) with an outlet tubing system to apply negative pressure to the mMS lumen thus pulling the spinal cord stumps into the honeycomb-structured holes. After its implantation into the 1 mm tissue gap the tissue is sucked into the device. Furthermore, the inner walls of the mMS are microstructured for better tissue adhesion. In the case of the chronic spinal cord injury approach, spinal cord tissue - including the scar-filled lesion area - is resected over an area of 4 mm in length. After the microsurgical scar resection the resulting cavity is filled with polyethylene glycol (PEG 600) which was found to provide an excellent substratum for cellular invasion, revascularization, axonal regeneration and even compact remyelination in vivo.Publicationtype: Journal Article88 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , A mechanical microconnector system for restoration of tissue continuity and long-term drug application into the injured spinal cord(Elsevier, 2013-10-03); ; ; ; Complete transection of the spinal cord leaves a gap of several mm which fills with fibrous scar tissue. Several approaches in rodent models have used tubes, foams, matrices or tissue implants to bridge this gap. Here, we describe a mechanical microconnector system (mMS) to re-adjust the retracted spinal cord stumps. The mMS is a multi-channel system of polymethylmethacrylate (PMMA), designed to fit into the spinal cord tissue gap after transection, with an outlet tubing system to apply negative pressure to the mMS thus sucking the spinal cord stumps into the honeycomb-structured holes. The stumps adhere to the microstructure of the mMS walls and remain in the mMS after removal of the vacuum. We show that the mMS preserves tissue integrity and allows axonal regrowth at 2, 5 and 19 weeks post lesion with no adverse tissue effects like in-bleeding or cyst formation. Preliminary assessment of locomotor function in the open field suggested beneficial effects of the mMS. Additional inner micro-channels enable local substance delivery into the lesion center via an attached osmotic minipump. We suggest that the mMS is a suitable device to adapt and stabilize the injured spinal cord after surgical resection of scar tissue (e.g., for chronic patients) or traumatic injuries with large tissue and bone damages.Publicationtype: Journal Article89 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Access status: without files , Rückenmarkadaptation : bioresorbierbares Mikrosystem, Medikamentenapplikation, Stammzellen(Springer, 2013-09-05); ; ; ; Background. The idea behind the research project on neuroregeneration after spinal cord injury currently funded by the Deutsche Gesetzliche Unfallversicherung (DGUV) is to combine known drug and cell therapeutic approaches with a surgical procedure. Technique. Damaged spinal cord tissue is resected followed by a tension-free adaptation of the uninjured tissue. For this purpose, a connector element (mMS, mechanical micro-connector system) was developed based on microsystem technologies. The mMS additionally allows the administration of drugs via microchannels Animal trials. In a key experiment in rats, the fixation of the spinal cord tissue, regenerative axon growth through the mMS, and improvement of locomotor function was shown. Currently, further therapeutic combination strategies include the use of substances to reduce fibrotic scar formation, to digest proteoglycans that inhibit axonal growth, stem cells to stimulate axonal growth as well as the chemokine SDF1. Discussion. In order to enable a tension-free adaptation of healthy tissue, depending on the extent of the damage, a shortening of the corresponding spine segment may be necessary. This can be achieved by total vertebral resection. It is known from the literature that total removal of spine segments is technically possible. However, shortening the spine in the course of the treatment of spinal cord damage is new. By combining cellular pharmaceutical treatments with surgical mechanical procedures the neuroregenerative therapy of spinal cord injury seems possible.Publicationtype: Journal Article86