Modification of tubular chitosan-based peripheral nerve implants: applications for simple or more complex approaches

Surgical treatment of peripheral nerve injuries is still a major challenge in human clinic.Up to now,none of the well-developed microsurgical treatment options is able to guarantee a complete restoration of nerve function.This restriction is also effective for novel clinically approved artificial nerve guides.In this review,we compare surgical repair techniques primarily for digital nerve injuries reported with relatively high prevalence to be valuable attempts in clinical digital nerve repair and point out their advantages and shortcomings.We furthermore discuss the use of artificial nerve grafts with a focus on chitosan-based nerve guides,for which our own studies contributed to their approval for clinical use.In the second part of this review,very recent future perspectives for the enhancement of tubular(commonly hollow)nerve guides are discussed in terms of their clinical translatability and ability to form three-dimensional constructs that biomimick the natural nerve structure.This includes materials that have already shown their beneficial potential in in vivo studies like fibrous intraluminal guidance structures,hydrogels,growth factors,and approaches of cell transplantation.Additionally,we highlight upcoming future perspectives comprising co-application of stem cell secretome.From our overview,we conclude that already simple attempts are highly effective to increase the regeneration supporting properties of nerve guides in experimental studies.But for bringing nerve repair with bioartificial nerve grafts to the next level,e.g.repair of defects>3 cm in human patients,more complex intraluminal guidance structures such as innovatively manufactured hydrogels and likely supplementation of stem cells or their secretome for therapeutic purposes may represent promising future perspectives.

Diabetes, its impact on peripheral nerve regeneration： lessons from pre-clinical rat models towards nerve repair and reconstruction

The global number of patients with type 1 and type 2 diabetes is about to increase substantially in the coming decades. The reasons for this are two-fold, at first there is actual increase in incidence of type 1 diabetes and at second there is global increase in living expectancy and a high prevalence of patients with type 2 diabetes among the elderly. The diabetic condition is affiliated with reduced peripheral nervous system maintenance, such as peripheral neuropathies （Juster-Switlyk and Smith, 2016） that may be more common in men.

Ex vivo limb perfusion for traumatic amputation in military medicine

Background:Limb loss has a drastic impact on a patient’s life.Severe trauma to the extremities is common in current military conflicts.Among other aspects,"life before limb"damage control surgery hinders immediate replantation within the short post-traumatic timeframe,which is limited in part by the ischemic time for successful replantation.Ex vivo limb perfusion is currently being researched in animal models and shows promising results for its application in human limb replantation and allotransplantation.Presentation of the hypothesis:The current lack of replantation possibilities in military operations with high rates of amputation can be addressed with the development of a portable ex vivo limb perfusion device,as there are several opportunities present with the introduction of this technique on the horizon.We hypothesize that ex vivo limb perfusion will enable overcoming the critical ischemic time,provide surgical opportunities such as preparation of the stump and limb,allow for spare-part surgery,enable rigorous antibiotic treatment of the limb,reduce ischemiareperfusion injuries,enable a tissue function assessment before replantation,and enable the development of large limb transplant programs.Testing the hypothesis:Data from in vivo studies in porcine models are limited by the relatively short perfusion time of 24 h.In the military setting,notably longer perfusion times need to be realized.Therefore,future animal studies must focus especially on long-term perfusion,since this represents the military setting,considering the time for stabilization of the patient until evacuation to a tertiary treatment center.Implications of the hypothesis:The development and clinical introduction of ex vivo limb perfusion in the military setting could lead to a drastic reduction in the number of limb amputations among service members.Ex vivo limb perfusion enables replantation surgery in Role 4 facilities and changes the clinical setting from a highly urgent,lifethreatening situation to a highly methodical,well-prepared starting point for optimal treatment of the wounded service member.With its introduction,the principle of"life before limb"will change to"life before limb before elective replantation/allotransplantation after ex vivo limb perfusion".