Abstract
Background: Severe peripheral nerve injury, especially the long-distance peripheral nerve defect, causes severe functional disability in patients. There is always a lack of effective repair methods for clinic, and those in practice are associated with side effects. A case study was performed to observe the regenerative outcomes of the surgical repair of long-distance peripheral nerve defects in the upper arm with chitosan-poly(glycolide-co-lactide) (PGLA) nerve grafts combined with bone marrow mononuclear cells (BMMCs).
Methods: The right upper arm of a 29-year-old woman was injured, leaving a 50-mm-long median nerve defect, an 80-mm-long ulnar nerve defect, and muscle and blood vessel disruptions. The nerve defects were repaired by implanting BMMC-containing chitosan-PGLA nerve grafts on the 40th day after injury. A series of functional assessments were carried out from 2 weeks to 66 months after surgical repair. Sensory function was assessed by the pinprick test, two-point discrimination test and Semmes-Weinstein monofilament test. Motor function was evaluated by the range of motion of the wrist joint and muscle power. Autonomic function was monitored by laser-Doppler perfusion imaging (LDPI). Tissue morphology was observed through ultrasonic investigations.
Results: No adverse events, such as infection, allergy, or rejection, caused by the treatment were detected during the follow-up period. Sensory and pinprick nociception in the affected thumb, index, and middle fingers gradually restored at 6th month after surgery. The monofilament tactile sensation was 0.4 g in the terminal finger pulp of the thumb and index finger, 2.0 g in the middle finger, and greater than 300 g in the ring finger and little finger at the 66th month. Motor function recovery was detected at the 5th month after surgery, when the muscle strength of the affected forearm flexors began to recover. At the 66th month after surgery, the patient's forearm flexor strength was grade 4, with 80° of palmar flexion, 85° of dorsal extension, 8° of radial deviation, 40° of ulnar deviation, 40° of anterior rotation, and 85° of posterior rotation of the affected wrist. The patient could perform holding, picking up, and some other daily activities with the affected hand. The patient's sweating function of the affected hand was close to the level of the healthy hand. LDPI showed that the skin blood flow perfusion was significantly increased, with perfusion similar to on the normal side in some areas. Neuromusculoskeletal ultrasonography showed the presence of nerve structures.
Conclusion: These results suggest that chitosan-PGLA nerve grafts combined with BMMCs could effectively repair long-distance nerve defects and achieve good clinical results.
Keywords: Long-distance nerve defect, chitosan-PGLA, bone marrow mononuclear cells, tissue engineering, nerve regeneration, neuromusculoskeletal.
Graphical Abstract
[http://dx.doi.org/10.1016/j.biomaterials.2014.04.064] [PMID: 24818883]
[http://dx.doi.org/10.1016/j.pneurobio.2010.10.002] [PMID: 20950667]
[http://dx.doi.org/10.1126/science.338.6109.900] [PMID: 23161989]
[http://dx.doi.org/10.1016/j.pneurobio.2010.11.002] [PMID: 21130136]
[http://dx.doi.org/10.1016/j.biomaterials.2003.11.029] [PMID: 15046917]
[http://dx.doi.org/10.1016/j.ymeth.2008.10.014] [PMID: 18952175]
[http://dx.doi.org/10.1093/brain/awh517] [PMID: 15872018]
[http://dx.doi.org/10.1016/j.biomaterials.2012.09.020] [PMID: 23063298]
[http://dx.doi.org/10.1007/s10529-008-9795-1] [PMID: 18612593]
[http://dx.doi.org/10.1002/term.407] [PMID: 21370489]
[http://dx.doi.org/10.1016/j.biomaterials.2017.01.044] [PMID: 28188997]
[http://dx.doi.org/10.1016/S0140-6736(04)16633-6] [PMID: 15246733]
[http://dx.doi.org/10.1016/j.cell.2018.09.010] [PMID: 30340033]
[http://dx.doi.org/10.1016/j.expneurol.2018.05.016] [PMID: 29772248]
[http://dx.doi.org/10.3727/096368916X690494] [PMID: 26777485]
[http://dx.doi.org/10.1177/1753193408090401] [PMID: 18687837]
[http://dx.doi.org/10.1038/nature06619] [PMID: 18322531]
[http://dx.doi.org/10.1089/107632703764664765] [PMID: 12740092]
[http://dx.doi.org/10.1016/S0140-6736(06)68438-9] [PMID: 16631879]
[http://dx.doi.org/10.1016/j.biomaterials.2018.07.017] [PMID: 30036727]
[http://dx.doi.org/10.1161/CIRCRESAHA.116.310277] [PMID: 28069694]
[http://dx.doi.org/10.1126/science.aab3388] [PMID: 26785478]
[http://dx.doi.org/10.1016/j.stem.2019.05.005] [PMID: 31173716]
[http://dx.doi.org/10.1016/j.stem.2015.12.005] [PMID: 26748754]
[http://dx.doi.org/10.1089/ten.tea.2010.0299] [PMID: 20666610]
[http://dx.doi.org/10.1177/1545968311420444] [PMID: 21947688]
[http://dx.doi.org/10.1016/j.jhsa.2005.03.017] [PMID: 16182055]
[http://dx.doi.org/10.1097/PRS.0000000000006485] [PMID: 31985643]
[http://dx.doi.org/10.1016/j.brainres.2015.10.045] [PMID: 26529641]