Osteoconductive and Carrier-Filled 3D Scaffolds for Bone Repair and Replacement

Objective:

To study designed 3D printed (direct-write) bone replacement scaffolds of hydroxyapatite (HA) and mixtures of HA and btri-calcium phosphate (bTCP), for custom replacement of bone structure in vitro and in vivo. These scaffolds comprise microstructural/macrostructural lattices for bone ingrowth. We have also filled these scaffolds with soluble filler materials (calcium sulfate, CS; and chitosan, CH) that protect the integrity of the scaffolds, rate limit tissue ingrowth, and may be carriers for bioactive molecules.

Methods: 3D Printing was used to produce several types of scaffolds with struts 250µm in diameter and pores of 250 and 400µm. Some were impregnated with CS or CH to temporarily fill the internal porosity. They were evaluated with regular cell culture methods, perfusion cell culture, and in vivo analysis (critical-sized, 11mm diameter x 3mm, trephine defects in rabbit parietal bones for 8 and 16 weeks). Light and scanning electron microscopy, histology, and micro-computed tomography were used to evaluate cell response, and tissue response to the structures.

Results: Cell culture studies showed excellent cell attachment and proliferation characteristics suggesting that the scaffolds are biocompatible. In vivo, HA scaffolds conducted bone across critical defects by 8 weeks, and soft tissue barriers prevented subcutaneous soft tissue invasion. Bone ingrowth (as % of available volume) ranged from 63.5-95.5%, and single bone trabeculae were observed to attach to and be conducted along individual scaffold struts. The fillers dissolved/degraded at rates consistent with tissue ingrowth both in vitro and in vivo.

Conclusions: Designed 3D scaffolds can be custom fabricated to conduct extensive bone ingrowth, and for lifetimes. The use of strut sizes similar to healing bone trabeculae result in rapid bone growth. HA/bTCP scaffolds, and scaffolds with soluble fillers can enhance stability, limit soft tissue ingrowth, and can be used to release bioactive molecules.