Fast-setting calcium phosphate scaffolds with tailored macropore formation rates for bone regeneration

Calcium phosphate cement (CPC) is highly promising for craniofacial and orthopedic repair because of its ability to self-harden in situ to form hydroxyapatite with excellent osteoconductivity. However, its low strength, long hardening time, and lack of macroporosity limit its use. This study aimed to develop fast-setting and antiwashout CPC scaffolds with high strength and tailored macropore formation rates. Chitosan, sodium phosphate, and hydroxypropyl methylcellulose (HPMC) were used to render CPC fast-setting and resistant to washout. Absorbable fibers and mannitol porogen were incorporated into CPC for strength and macropores for bone ingrowth. Flexural strength, work-of-fracture, and elastic modulus were measured vs. immersion time in a physiological solution. Hardening time (mean +/- SD; n = 6) was 69.5 +/- 2.1 min for CPC-control, 9.3 +/- 2.8 min for CPC-HPMC-mannitol, 8.2 +/- 1.5 min for CPC-chitosan-mannitol, and 6.7 +/- 1.6 min for CPC-chitosan-mannitol-fiber. The latter three compositions were resistant to washout, whereas the CPC-control paste showed washout in a physiological solution. Immersion for 1 day dissolved mannitol and created macropores in CPC. CPC-chitosan-mannitol-fiber scaffold had a strength of 4.6 +/- 1.4 MPa, significantly higher than 1.2 +/- 0.1 MPa of CPC-chitosan-mannitol scaffold and 0.3 +/- 0.2 MPa of CPC-HPMC-mannitol scaffold (Tukey's). The strength of CPC-chitosan-mannitol-fiber scaffold was maintained up to 42 days and then decreased because of fiber degradation. Work-of-fracture and elastic modulus showed similar trends. Long cylindrical macropore channels were formed in CPC after fiber dissolution. The resorbable, fast-setting, anti-washout and strong CPC scaffold should be useful in craniofacial and orthopedic repairs. The novel method of combining fast- and slow-dissolution porogens/fibers to produce scaffolds with high strength and tailored macropore formation rates to match bone healing rates may have wide applicability to other biomaterials.