Quantitative evaluation of the in vivo biocompatibility and performance of freeze-cast tissue scaffolds

: Little used for the in vivo assessment of tissue scaffolds are quantitative methods for the evaluation of biocompatibility. To complement current histological techniques, we introduce a histomorphometric approach for the quantitative assessment of encapsulation thickness, cross-sectional area and shape of biomaterials and characteristics of their biomaterial-tissue interface in vivo as additional criteria for biocompatibility. Advantages of this new technique are that it enables a more complete and objective comparison of scaffold biocompatibility with differing compositions, architectures, and mechanical properties, on the one hand, and that it enables a more objective approach to their selection for a given application on the other. In this contribution, we focus on freeze-cast polymeric scaffolds for tissue regeneration and their subcutaneous implantation in mice for biocompatibility testing. Initially, seven different scaffold types are screened. Of these, three are selected for systematic biocompatibility studies based on histopathological criteria: EDC-NHS-crosslinked bovine collagen, EDC-NHS-crosslinked bovine collagen-nanocellulose, and chitin. Geometric models developed to quantify scaffold size, ovalization, and encapsulation thickness are evaluated as an objective metric to assess the in vivo performance of scaffolds and their biocompatibility.