Repair of craniofacial bone restores form and function and enhances quality of life. Tissue response to bone-replacement scaffolds depends on a complex set of interactions between scaffold features and materials. Changes in any one can affect the tissue response - sometimes dramatically. Objective: to compare bone response to scaffold architecture features and materials. Methods: Scaffolds 8 mm-diameter x 3 mm thick were fabricated using 3D printing from high molecular weight (200 KDa) (polylactic-co-glycolic acid (PLGA) with lactic/glycolic ratio of 50:50 and 20% tricalcium phosphate (TCP) and from poly(desamino-tryosyl tyrosine ethyl ester carbonate) (PDTEC). Micro- and meso-architectures (feature sizes from tens to hundreds of mm) were controlled to produce 4 groups: (G1) microporous PLGA/TCP scaffolds with graded porosity from 80% at the calvarial surface to 87.5% at the dural surface, with 1 mm square x 2 mm deep axial channels (from the dural surface) and 1.6 mm x 1 mm radial channels, (G2) PDTE with G1 configuration, (G3) PDTE with interlayer pores of 500 mm with supporting struts of 500 mm and layer heights of 500 mm, and (G4) G3 meso-architecture but with 80% wall porosity. Scaffolds were implanted in trephine defects in skeletally mature NZW rabbits; bone response was evaluated radiographically and hiostomorphometrically at 8 and 16 weeks (n=6). Results: At 16 weeks, inductive index (total linear amount of bone/total scaffold width) was 0.23 (G3), 0.19 (G4), 0.12 (G2), 0.06 (G1) (p=0.01 for G3 vs. G1; p=0.055 for G4 vs. G1; others NS). Patterns of bone ingrowth mimicked scaffold meso-geometry. Rate of bone ingrowth was the same for all architectures. Conclusion: Amount and pattern of tissue filling a bone-replacement scaffold can be modified by material and scaffold meso-geometry.

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