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The large number of animal models used in spinal cord injury (SCI) research complicates the objective selection of the most appropriate model to investigate the efficacy of biomaterial-based therapies. This systematic review aims to identify a list of relevant animal models of SCI by evaluating the confirmation of SCI and animal survival in all published SCI models used in biomaterials research up until April 2021. A search in PubMed and Embase based on "spinal cord injury," "animal models," and "biomaterials" yielded 4606 papers, 393 of which were further evaluated. A total of 404 individual animal experiments were identified based on type of SCI, level of SCI, and the sex, species, and strain of the animals used. Finally, a total of 149 unique animal models were comparatively evaluated, which led to the generation of an evidence-based list of well-documented mid-thoracic rat models of SCI. These models were used most often, clearly confirmed SCI, and had relatively high survival rates, and therefore could serve as a future starting point for studying novel biomaterial-based therapies for SCI. Furthermore, the review discusses (1) the possible risk of bias in SCI animal models, (2) the difficulty in replication of such experiments due to frequent poor reporting of the methods and results, and (3) the clinical relevance of the currently utilized models. Systematic review registration : The study was prospectively registered in PROSPERO, registration number CRD42019141162. Impact statement Studies on biomaterial-based therapies within the field of spinal cord injury (SCI) research show a large inconsistency concerning the selection of animal models. This review goes beyond summarizing the existing gaps between experimental and clinical SCI by systematically evaluating all animal models used within this field. The models identified by this work were used most often, clearly confirmed SCI, and had a relatively high survival rate. This evidence-based list of well-documented animal models will serve as a practical guideline in future research on innovative biomaterial-based therapies for SCI.

Micro- and nanotextured biomaterial surfaces have been widely studied for their capacity to drive the regeneration of organized tissues. Nanotopographical features in the shape of groove-ridge patterns aim at mimicking the extracellular matrix organization. However, to date, a wide array of groove and ridge sizes has been described. In this work, we therefore tested a device composed of a multipatterned array consisting of six patterns of radially arranged parallel nanogrooves, with a pitch ranging from 0 to 1000 nm and a depth ranging from 0 to 170 nm, to be used as a tool for the expeditious and simultaneous screening of surface topographies aiming the regeneration of anisotropically organized tissues such as ligament. The topographies were reproduced in (1) epoxy resin or (2) membranes produced by the crosslinking of platelet lysate (PL) with genipin (gPL). Both materials were seeded with periodontal ligament cells (PDLCs) and the proliferation, migration, as well as cell alignment were assessed. The effect of topography in PDLCs was only evident in terms of cell organization, resulting in a highly anisotropic organization of the cells for the 1000 and 600 nm patterns, and in an increased isotropic organization for shallower topographies. Overall, our results suggest that this multipatterned system can be a valuable diagnostic tool for biomaterials aiming at the regeneration of anisotropically organized tissues, such as periodontal ligament.

This study investigated whether cells have an intrinsic ability to recognize nanopatterns, which could lead to their accumulation or diminution on a biomaterial. A multi-patterned "biochip" was made, containing 36 differently designed surfaces, including squares and grooves varying in feature sizes between 10 and 1000 nm. The grooved patterns could additionally be subdivided into three groups having ridge to groove ratios of 1:1, 1:3 and 3:1. These substrates were used for culture of rat bone marrow derived mesenchymal cells. In time cells should accumulate on patterns of preference, while migrating away from patterns of disfavor. A regression analysis model was designed for the analysis of the obtained data. Results showed that strong differences existed between the tested patterns regarding the cellular affinity. All sizes of squares showed strong cell-repelling capacity, with the biggest sized squares displaying up to 40% less cells compared to the smooth surface. Among the nano-grooved patterns cell repelling was seen for the grooves with the ridge to groove ratio of 1:3, while grooves with the ridge to groove ratio of 3:1 partially showed cell attraction. Such effects were shown to be based on selective migration rather than proliferation. In conclusion, the use of a multi-patterned biochip setup allows for enhanced evaluation of cell behavior, as compared to uniformly patterned setups. Cells exhibit the ability to actively avoid or migrate to surfaces featuring certain topographies on nanometric scale. Such phenomena may be utilized for the development of biomaterials in regenerative medicine., (Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The search for alternative therapies to improve bone regeneration continues to be a major challenge for the medical community. Here we report on the enhanced mineralization, osteogenesis, and in vivo bone regeneration properties of a bioactive elastin-like recombinamer (ELR) membrane. Three bioactive ELRs exhibiting epitopes designed to promote mesenchymal stem cell adhesion (RGDS), mineralization (DDDEEKFLRRIGRFG), and both cell adhesion and mineralization were synthesized using standard recombinant protein techniques. The ELR materials were then used to fabricate membranes comprising either a smooth surface (Smooth) or channel microtopographies (Channels). Mineralization and osteoblastic differentiation of primary rat mesenchymal stem cells (rMSCs) were analyzed in both static and dynamic (uniaxial strain of 8% at 1 Hz frequency) conditions. Smooth mineralization membranes in static condition exhibited the highest quantity of calcium phosphate (Ca/P of 1.78) deposition with and without the presence of cells, the highest Young's modulus, and the highest production of alkaline phosphatase on day 10 in the presence of cells growing in non-osteogenic differentiation medium. These membranes were tested in a 5 mm-diameter critical-size rat calvarial defect model and analyzed for bone formation on day 36 after implantation. Animals treated with the mineralization membranes exhibited the highest bone volume within the defect as measured by micro-computed tomography and histology with no significant increase in inflammation. This study demonstrates the possibility of using bioactive ELR membranes for bone regeneration applications., (Copyright © 2014 Elsevier Ltd. All rights reserved.)