Synergistic reinforcement of in situ hardening calcium phosphate composite scaffold for bone tissue engineering

Abstract

Calcium phosphate cement (CPC) hardens in situ to form solid hydroxyapatite, can conform to complex cavity shapes without machining, has excellent osteoconductivity, and is able to be resorbed and replaced by new bone. Therefore, CPC is promising for use in craniofacial and orthopaedic repairs. However, the low strength and lack of macroporosity of CPC limit its use. The aim of the present study was to increase the strength and toughness of CPC while creating macropores suitable for cell infiltration and bone ingrowth, and to investigate the effects of chitosan and mesh reinforcement on the composite properties. Specimens were self-hardened in 3 mm×4 mm×25 mm molds, immersed in a physiological solution for 1–84 d, and tested in three-point flexure. After 1 d, the unreinforced CPC control had a flexural strength (mean±s.d.; n=6) of (3.3±0.4) MPa. The incorporation of chitosan or mesh into CPC increased the strength to (11.9±0.8) and (21.3±2.7) MPa, respectively. The incorporation of both chitosan and mesh synergistically into CPC dramatically increased the strength to (43.2±4.1) MPa. The work-of-fracture (WOF) (toughness) was also increased by two orders of magnitude. After 84 d immersion in a simulated physiological solution, the meshes in CPC dissolved and formed interconnected cylindrical macropores. The novel CPC scaffold had a flexural strength 39% higher, and WOF 256% higher than the conventional CPC without macropores. The new composite had an elastic modulus within the range for cortical bone and cancellous bone, and a flexural strength higher than those for cancellous bone and sintered porous hydroxyapatite implants. In conclusion, combining two different reinforcing agents together in self-hardening CPC resulted in superior synergistic strengthening compared to the traditional use of a single reinforcing agent. The strong and macroprous CPC scaffold may be useful in stress-bearing craniofacial and orthopaedic repairs.