title: Combining microCT-based characterization with empirical modelling as a robust screening approach for the design of optimized CaP-containing scaffolds for progenitor cell-mediated bone formation.
abstract: Biomaterials are a key ingredient to the success of bone tissue engineering (TE), which focuses on the healing of bone defects by combining scaffolds with cells and/or growth factors. Due to the widely variable material characteristics and patient-specificities, however, current bone TE strategies still suffer from low repeatability and lack of robustness, which hamper clinical translation. Hence, optimal TE construct (i.e. cells and scaffold) characteristics are still under debate. This study aimed to reduce the material-specific variability for cell-based construct design, avoiding trial-and-error, by combining microCT characterization and empirical modelling as an innovative and robust screening approach. Via microCT characterization we have built a quantitative construct library of morphological and compositional properties of six CE approved CaP-based scaffolds (CopiOs®, BioOss™, Integra Mozaik™, chronOS Vivify, MBCP™ and ReproBone™), and of their bone forming capacity and in vivo scaffold degradation when combined with human periosteal derived cells (hPDCs). The empirical model, based on the construct library, allowed identification of the construct characteristics driving optimized bone formation, i.e. (a) the percentage of β-TCP and dibasic calcium phosphate, (b) the concavity of the CaP structure, (c) the average CaP structure thickness and (d) the seeded cell amount (taking into account the seeding efficiency). Additionally, the model allowed to quantitatively predict the bone forming response of different hPDC-CaP scaffold combinations, thus providing input for a more robust design of optimized constructs and avoiding trial-and error. This could improve and facilitate clinical translation.
  
  
  CONCLUSIONS
  Biomaterials that support regenerative processes are a key ingredient for successful bone tissue engineering (TE). However, the optimal scaffold structure is still under debate. In this study, we have provided a useful innovative approach for robust screening of potential biomaterials or constructs (i.e. scaffolds seeded with cells and/or growth factors) by combining microCT characterization with empirical modelling. This novel approach leads to a better insight in the scaffold parameters influencing progenitor cell-mediated bone formation. Additionally, it serves as input for more controlled and robust design of optimized CaP-containing bone TE scaffolds. Hence, this novel approach could improve and facilitate clinical translation.
authors.affiliation: Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Onderwijs en Navorsing 1, Herestraat 49 - PB813, B-3000 Leuven, Belgium; Tissue Engineering Laboratory, Skeletal Biology and Engineering Research Center, KU Leuven, Onderwijs en Navorsing 1, Herestraat 49 - PB813, B-3000 Leuven, Belgium. Electronic address: greet.kerckhofs@med.kuleuven.be.
authors.forename: G
authors.initials: G
authors.lastname: Kerckhofs
authors.affiliation: Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Onderwijs en Navorsing 1, Herestraat 49 - PB813, B-3000 Leuven, Belgium; Tissue Engineering Laboratory, Skeletal Biology and Engineering Research Center, KU Leuven, Onderwijs en Navorsing 1, Herestraat 49 - PB813, B-3000 Leuven, Belgium. Electronic address: yoke.chin.chai@vub.ac.be.
authors.forename: Y C
authors.initials: YC
authors.lastname: Chai
authors.affiliation: Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Onderwijs en Navorsing 1, Herestraat 49 - PB813, B-3000 Leuven, Belgium; Tissue Engineering Laboratory, Skeletal Biology and Engineering Research Center, KU Leuven, Onderwijs en Navorsing 1, Herestraat 49 - PB813, B-3000 Leuven, Belgium. Electronic address: frank.luyten@uz.kuleuven.be.
authors.forename: F P
authors.initials: FP
authors.lastname: Luyten
authors.affiliation: Prometheus, Division of Skeletal Tissue Engineering, KU Leuven, Onderwijs en Navorsing 1, Herestraat 49 - PB813, B-3000 Leuven, Belgium; Biomechanics Research Unit, Université de Liège, Chemin des Chevreuils 1 - BAT 52/3, B-4000 Liège, Belgium; Division of Biomechanics and Engineering Design, KU Leuven, Celestijnenlaan 300C, B-3001 Heverlee, Belgium. Electronic address: liesbet.geris@ulg.ac.be.
authors.forename: L
authors.initials: L
authors.lastname: Geris
mesh_terms: D000293:Adolescent; D000818:Animals; D002130:Calcium Phosphates / Q000494:pharmacology*; D002452:Cell Count; D002648:Child; D003094:Collagen / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D008819:Mice, Nude; D010012:Osteogenesis / Q000187:drug effects*; D016062:Porosity; D013234:Stem Cells / Q000166:cytology*; D054457:Tissue Scaffolds / Q000737:chemistry*; D055114:X-Ray Microtomography / Q000379:methods*
chemical_list: D002130:Calcium Phosphates; D003094:Collagen; C020243:calcium phosphate
keywords: Empirical modelling; MicroCT characterization; Optimized calcium phosphate-based constructs; Robust screening