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Development and Characterization of Heparin-Containing Hydrogel/3D-Printed Scaffold Composites for Craniofacial Reconstruction

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Abstract

Regeneration of cartilage and bone tissues remains challenging in tissue engineering due to their complex structures, and the need for both mechanical support and delivery of biological repair stimuli. Therefore, the goal of this study was to develop a composite scaffold platform for anatomic chondral and osteochondral repair using heparin-based hydrogels to deliver small molecules within 3D-printed porous scaffolds that provide structure, stiffness, and controlled biologic delivery. We designed a mold-injection system to combine hydrolytically degradable hydrogels and 3D-printed scaffolds that could be employed rapidly (< 30 min) in operating room settings (~23 °C). Micro-CT analysis demonstrated the effectiveness of our injection system through homogeneously distributed hydrogel within the pores of the scaffolds. Hydrogels and composite scaffolds exhibited efficient loading (~94%) of a small positively charged heparin-binding molecule (crystal violet) with sustained release over 14 days and showed high viability of encapsulated porcine chondrocytes over 7 days. Compression testing demonstrated nonlinear viscoelastic behavior where tangent stiffness decreased with scaffold porosity (porous scaffold tangent stiffness: 70%: 4.9 MPa, 80%: 1.5 MPa, and 90%: 0.20 MPa) but relaxation was not affected. Lower-porosity scaffolds (70%) showed stiffness similar to lower ranges of trabecular bone (4–8 MPa) while higher-porosity scaffolds (80% and 90%) showed stiffness similar to auricular cartilage (0.16–2 MPa). Ultimately, this rapid composite scaffold fabrication method may be employed in the operating room and utilized to control biologic delivery within load-bearing scaffolds.

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Acknowledgments

The authors would like to thank Sarah Jo Tucker for her assistance in printing and cleaning the 3D-printed scaffolds and Dr. Laxminarayanan Krishnan for his guidance in performing µCT scans and analysis. This work was supported by the Carol Ann and David D. Flanagan Professorship and Patsy and Alan Dorris Chair in Pediatric Technology.

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  1. Wallace H. Coulter Department of Biomedical Engineering, Georgia Tech and Emory University, 313 Ferst Dr, Atlanta, GA, 30332, USA

    Nettie E. Brown, Lela R. Ellerbe, Scott J. Hollister & Johnna S. Temenoff

  2. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr, Atlanta, GA, 30332, USA

    Johnna S. Temenoff

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Correspondence to Scott J. Hollister or Johnna S. Temenoff.

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This work was supported by the Carol Ann and David D. Flanagan Professorship and Patsy and Alan Dorris Chair in Pediatric Technology. The authors have no competing interests to declare that are relevant to the content of this article.

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Brown, N.E., Ellerbe, L.R., Hollister, S.J. et al. Development and Characterization of Heparin-Containing Hydrogel/3D-Printed Scaffold Composites for Craniofacial Reconstruction. Ann Biomed Eng (2024). https://doi.org/10.1007/s10439-024-03530-z

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