No abstract

Injury to nerve tissue in the peripheral nervous system (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss of sensation from the tissue innervated by the harvested nerve. The challenges that persist with nerve repair have resulted in development of nerve guides or conduits from non-neural biological tissues and various polymers to improve the prognosis for the repair of damaged nerves in the PNS. This study describes the design and fabrication of a multimodal controlled pore size nerve regeneration conduit using polylactic acid (PLA) and (PLA):poly(lactic-coglycolic) acid (PLGA) fibers within a neurotrophin-enriched alginate hydrogel. The nerve repair conduit design consists of two types of PLGA fibers selected specifically for promotion of axonal outgrowth and Schwann cell growth (75:25 for axons; 85:15 for Schwann cells). These aligned fibers are contained within the lumen of a knitted PLA sheath coated with electrospun PLA nanofibers to control pore size. The PLGA guidance fibers within the nerve repair conduit lumen are supported within an alginate hydrogel impregnated with neurotrophic factors (NT-3 or BDNF with LIF, SMDF and MGF-1) to provide neuroprotection, stimulation of axonal growth and Schwann cell migration. The conduit was used to promote repair of transected sciatic nerve in rats over a period of 4 weeks. Over this period, it was observed that over-grooming and self-mutilation (autotomy) of the limb implanted with the conduit was significantly reduced in rats implanted with the full-configuration conduit compared to rats implanted with conduits containing only an alginate hydrogel. This indicates return of some feeling to the limb via the fully-configured conduit. Immunohistochemical analysis of the implanted conduits removed from the rats after the four-week implantation period confirmed the presence of myelinated axons within the conduit and distal to the site of implantation, further supporting that the conduit promoted nerve repair over this period of time. This study describes the design considerations and fabrication of a novel multicomponent, multimodal bio-engineered synthetic conduit for peripheral nerve repair. AbstractInjury to nerve tissue in the Peripheral Nervous System (PNS) results in long-term impairment of limb function, dysaesthesia and pain, often with associated psychological effects. Whilst minor injuries can be left to regenerate without intervention and short gaps up to 2 cm can be sutured, larger or more severe injuries commonly require autogenous nerve grafts harvested from elsewhere in the body (usually sensory nerves). Functional recovery is often suboptimal and associated with loss ...

Antibodies to Rhesus (Rh) antigens are important indicators in screening for haemolytic disease of the new‐born (HDN) and autoimmune haemolytic anaemia (AIHA). Identification of the Rh antibodies formed by immune stimulation is also essential in order to maximize the in vivo survival time of transfused erythrocytes. Currently this is performed by agglutination based assays that are time consuming. A prototype of an immuno‐biosensor for detecting antibodies recognizing the Rhesus blood group antigen, Rh (D), was constructed. Human erythrocytes were incorporated into a conducting polypyrrole, polyelectrolyte matrix. The process was followed by using oximetry and light microscopy to demonstrate the integrity of the erythrocytes in the polymerization solution and in the polymer matrix; cyclic voltammetry and resistometry for electrochemical characterization of the polymer and then agglutination, ELISA techniques and cyclic resistometry for analysis of the immuno response from antigen/antibody binding. Antigen/antibody binding could be detected qualitatively by using resistometry while cycling the polymer between +0.35 V and –0.7 V (vs. Ag/AgCl). A characteristic cyclic change in resistance (a resistogram) was recorded. After addition of Anti‐Rh (D) antibody (250 µg/mL), the change in resistance during the resistogram decreased by 1.1 Ω (p<0.0008) in polymers containing Rh (D) positive erythrocytes, whereas polymers without erythrocytes showed no significant change.