Reconstruction of damaged nerves remains a significant unmet challenge in clinical medicine. Topographical and mechanical stimulations play important roles to repair peripheral nerve injury. The synergistic effects of topography and mechanical rigidity may significantly accelerate nerve regeneration. In this work, a nerve-guiding collagen/polylactic acid (PLA) electrospun scaffold is developed to facilitate peripheral nerve repair. The obtained anisotropic PLA electrospun scaffolds simulate the directional arranged structure of nerve realistically and promote axonal regeneration after sciatic nerve injury when compared with the isotropic PLA electrospun scaffolds. Moreover, the collagen-modified PLA electrospun scaffolds further provide sufficient mechanical support and favorable microenvironment for axon regeneration. In addition, it is observed that collagen-modified PLA electrospun scaffolds facilitate the axon regeneration by regulating Yes-associated protein (YAP) molecular pathway. Taken together, the engineered collagen-modified anisotropic PLA electrospun scaffolds may be a potential candidate to combine topography and mechanical rigidity for peripheral nerve regeneration is engineered.

To assess clinical efficacy and cost-effectiveness of human recombinant interferon-␣2b in neonates with intrauterine infections in neonatal intensive care unit (NICU). METHODS: We observed 151 neonates (gestational age (GA) 25-40 weeks) with severe intrauterine infections in NICU. Group 1 included 94 neonates with severe intrauterine infections treated with interferon-␣2b, 150 000 IU per suppositorium twice a day per rectum during 7 days in addition to combined antibacterial and supportive therapy; group 2 consisted of 57 neonates under standard treatment without additional immunotherapy. Initially neonates of both groups were comparable. Effectiveness data were used to populate a decision model to estimate the cost-effectiveness of interferon-␣2b and standard therapy. Direct and indirect costs were measured. Published cost data were applied to assess differences in treatment costs. RESULTS: Low mitogen-induced interferon-␣ production (Ͻ12 pg/ml) was detected in 25% [18%; 33%] of neonates with severe intrauterine infections, its association with significantly higher incidence of pneumonia ( Ͻ0.001), necrotizing enterocolitis ( Ͻ0.001) and urinary tract infections ( ϭ0.026) was proved. Administration of human recombinant interferon-␣2b to neonates, suffering from severe infections, provides improvement of mitogen-induced production of interferon-␣, reduces hospital length of stay and mortality rates ( ϭ0.009, OR ϭ 0.21 [0.05; 0.67], RR ϭ 0.26 [0.07; 0.69], NNTϭ8 [4; 29]). Interferon-␣2b administration for severe early-onset neonatal infections decreases direct costs per patient by 20% (direct costs per patient € 6,802 and € 8,549 for interferon-␣2b and control groups, respectively). Interferon-␣2b administration for intrauterine infections leads to substantial cost savings (up to € 69,247 per patient). CONCLUSIONS: Immunotherapy with interferon-␣2b is a cost-effective intervention improves the clinical course and outcome in case of severe intrauterine infections.