In Vivo High-Content Evaluation of Three-Dimensional Scaffolds Biocompatibility

Abstract

While developing tissue engineering strategies, inflammatory response caused by biomaterials is an unavoidable aspect to be taken into consideration, as it may be an early limiting step of tissue regeneration approaches. We demonstrate the application of flat and flexible films exhibiting patterned high-contrast wettability regions as implantable platforms for the high-content in vivo study of inflammatory response caused by biomaterials. Screening biomaterials by using high-throughput platforms is a powerful method to detect hit spots with promising properties and to exclude uninteresting conditions for targeted applications. High-content analysis of biomaterials has been mostly restricted to in vitro tests where crucial information is lost, as in vivo environment is highly complex. Conventional biomaterials implantation requires the use of high numbers of animals, leading to ethical questions and costly experimentation. Inflammatory response of biomaterials has also been highly neglected in high-throughput studies. We designed an array of 36 combinations of biomaterials based on an initial library of four polysaccharides. Biomaterials were dispensed onto biomimetic superhydrophobic platforms with wettable regions and processed as freeze-dried three-dimensional scaffolds with a high control of the array configuration. These chips were afterward implanted subcutaneously in Wistar rats. Lymphocyte recruitment and activated macrophages were studied on-chip, by performing immunocytochemistry in the miniaturized biomaterials after 24 h and 7 days of implantation. Histological cuts of the surrounding tissue of the implants were also analyzed. Localized and independent inflammatory responses were detected. The integration of these data with control data proved that these chips are robust platforms for the rapid screening of early-stage in vivo biomaterials' response.

Natural polymers for the microencapsulation of cells

“…Alginates can also be combined with other biopolymers to improve the biological response of the host. Such studies were recently performed using high-throughput methodologies for the evaluation of the in vitro [95] and in vivo [96] response to different combinations of biomaterials. Furthermore, alginate does not provide cell adhesion motifs, but it can be conjugated with RGD peptides to improve cell adhesion [97].…”

Decellularized Bovine Articular Cartilage Matrix Reinforced by Carboxylated-SWCNT for Tissue Engineering Application

“…Bettinger et al (2009) proved that collagen-rich nanostructure bone and hydroxyapatite natural ECM take part in cell matrix signaling. Topographic signs in micro or Nano-dimension are among the preliminary mediators for surface absorption of proteins from the surrounding environment that mediate the process of cell attachment (Oliveira et al 2014). Controlling these properties can improve cell behavior.…”

High-throughput screening for integrative biomaterials design: exploring advances and new trends

“…Polystyrene chips based on wettability contrast containing miniaturized biomaterials were also implanted in Wistar rats for the assessment of localized early inflammatory response in a high-throughput context ( Figure 1) [10].…”

“…The dependence of automated equipment for the patterning of biomaterials/cells in the platforms used for high-throughput screening (HTS) will be compared with techniques that allow for bench-top dispensing of biomaterials [7][8][9]. A recent trend consisting of the implantation of biomaterial arrays in animal models will also be explored ( Figure 1) [10]. Single cell encapsulation in biomaterial microparticles will also be addressed, as it is fast becoming an easily up-scalable method for the study of biomaterials [11].…”