22Onchocerciasis also known as river blindness is a neglected tropical disease and the 23 world's second-leading infectious cause of blindness in humans; it is caused by 42 a valuable source of O. volvulus worms at various developmental stages, which may 43 accelerate innovative unsolved biomedical inquiries into the parasite's biology. 3 44 Author summary 45 The filarial nematode Onchocerca volvulus is an obligatory human parasite and the 46 causative agent of onchocerciasis, better known as river blindness. In 2017, more than 47 20 million infections with O. volvulus were estimated worldwide, 99 % of the patients live 48 in Africa. Current international control programs focus on the reduction of microfilaridermia 49 by mass drug administration of ivermectin. However, to meet the elimination goals, 50 additional therapy strategies are needed that also target the adult worms. As this parasite 51 is obliged to humans, there are no small animal models that sustain the full life cycle of 52 the parasite, thus greatly impeding the research on this filarial nematode. To overcome 53 these drawbacks, we developed co-culture systems based on engineered human skin and 54 adipose tissue that represent the in vivo niche of O. volvulus in which we were able to 55 establish improved conditions of culturing to the pre-adult stages of the parasite. 56 Furthermore, our new culture approach could significantly reduce the use of animal 57 models currently used for drug testing of surrogate larvae. 58 59 60 4 61 73 microfilariae reach ocular tissues, e.g. the cornea and the conjunctiva, they induce an 74 immunopathologic reaction, which can result in blindness after many years of chronic 75 infection [6]. 76 77 Current international control programs focus on the reduction of microfilaridermia by mass 78 drug administration of ivermectin annually or biannually for more than 10 -15 years. 79 However, adult O. volvulus worms can live in infected humans within the nodules for over 80 15 years, and this entails a prolonged treatment course of ivermectin. The goal is to 81 interrupt transmission of the parasite from human to human. Even the success achieved 82 thus far [7-9], it must now be weighed against the fact that since 1995 only a 31 % 83 reduction in the incidence of onchocerciasis has been achieved in Africa [10]. Optimists 5 84 call for additional 1.15 billion treatments to achieve elimination by 2045 [1]. Mathematical 85 modelling and expert opinions are more pessimistic, indicating that onchocerciasis in 86 Africa cannot be eliminated solely through mass drug administration with ivermectin alone 87 [11], especially as this strategy cannot be applied in 11 Central African countries that are 88 co-endemic with Loa loa infections; application of ivermectin may entail the risk of severe 89 adverse events [12,13]. In 2014, the African Programme for Onchocerciasis Control called 90 for the development and testing of new intervention technologies [14]. An alternative to 91 the reduction of the microfilariae load is to target its sou...