Repair of Complex Craniofacial Bone Defects Using 3D-Printed Tricalcium Phosphate Scaffolds
Repair of bone lost to trauma, disease, or birth defect requires regeneration of large volumes of structurally complex bone. Current bone repair methods, like bone grafts or particulate materials, are imperfect for repair of complex craniofacial defects which require formation of large amounts of natural, mechanically strong bone. 3D-printed, Direct Write (DW), scaffolds composed of tricalcium phosphate (TCP) with temporary calcium sulfate filler can serve as a better option to repair large complex bone defects. Such scaffolds are mechanically stable and can be custom printed to match the exact defect shape and size. Current literature debates scaffold pore sizes for optimal bone repair, stating scaffold pore size should be from 100-400µm. The objective of this study is to determine how pore size dictates the quality of ingrowing bone. This will allow the design of scaffolds that can regenerate the natural architecture and mechanical properties of bone in complex craniofacial defects.
Scaffold pores (spaces defined by struts) varied in all dimensions. Two 11mm diameter disk scaffold designs were DW printed of 15:85 HAP/β-TCP ink and filled with temporary calcium sulfate(CS) cement. These two designs allowed the study of pores from ~0-940 µm. The two scaffolds were placed symmetrically in bilateral trephine defects in the calvarias of 8 New Zealand white rabbits. Animals were sacrificed after 8 weeks (n=7) and 16 weeks (n=1). Bone ingrowth and remodeling rates of resected implants were quantified by microCT and hard tissue histology.
Contrary to previous literature findings, significant bone ingrowth occurred in pores ranging from 20µm to 940µm. Larger pore sizes allowed more bone ingrowth than smaller pore sizes. As pore size decreased, bone as a fraction of available space increased from 55%-85% and scaffold remodeling decreased from 32%-5%.
This study demonstrated precision scaffold production where variable porosity scaffolds were used to determine the relationship between pore size and the quality of bone repair and scaffold remodeling. The results showed that 3D printed tricalcium phosphate scaffolds can be used to grow bone across 11 mm voids in 8 weeks. Bone can grow into pores as large as 940 µm and as small as 20 µm. Each pore size allowed for a unique bone morphology and scaffold remodeling rate. Data on the effect of pore size on bone morphology and density can guide the selection of pore sizes for clinical scaffolds that can regenerate bone with organized cortical and trabecular-like anatomy. Data on how pore size dictates remodeling rates can allow design of scaffolds for patients requiring unique remodeling characteristics, e.g. children or osteoporotic patients. Future experiments will involve repair of a rabbit maxilla defect that closely resembles the bone loss in a child’s cleft palate or an edentulous adult’s atrophic alveolar ridge. Scaffolds designed to fit this defect will contain an architecture of pore sizes organized using the results from this study. The purpose will be to determine if the selection of pore sizes and their anatomical organization can regenerate and augment the natural architecture of alveolar bone in the functionally loaded maxilla. The findings from this study and its translation into oral and maxillofacial surgery will lay the groundwork for custom 3D-printing of scaffolds for the repair of the diverse craniofacial defects seen in humans.
Ricci JL, Clark EA, Murriky A, Smay JE. Three-dimensional printing of bone repair and replacement materials: Impact on craniofacial surgery. J Craniofacial Surg. 23:1, 2012
LeGeros, RZ . Properties of osteoconductive biomaterials: Calcium phosphates. Clin Orthop Relat Res 395:81-98, 2002