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

Abstract

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.

Human Embryonic Stem Cell-Derived Mesenchymal Stem Cell Seeding on Calcium Phosphate Cement-Chitosan-RGD Scaffold for Bone Repair

“…42 The previous studies did not report RGD incorporation into CPC. 39,42 In the present study, two types of chitosan were used: chitosan malate (Halosource, Redmond, WA) and RGD-modified chitosan malate.…”

“…Chitosan has been shown to strengthen CPC, 39 resist the washout of CPC paste in a physiological solution, and cause fast-setting to CPC. 42 Hence, the CPC liquid consisted of chitosan mixed with distilled water at a chitosan/(chitosan + water) mass fraction of 15%. 42 The previous studies did not report RGD incorporation into CPC.…”

“…42 Hence, the CPC liquid consisted of chitosan mixed with distilled water at a chitosan/(chitosan + water) mass fraction of 15%. 42 The previous studies did not report RGD incorporation into CPC. 39,42 In the present study, two types of chitosan were used: chitosan malate (Halosource, Redmond, WA) and RGD-modified chitosan malate.…”

“…Following a previous study, the specimen was scrubbed gently with fingers. 42 This was done at 1-min intervals until the powder component did not come off from the specimen. This indicates that the setting reaction had occurred sufficiently to hold the specimen together.…”

“…This indicates that the setting reaction had occurred sufficiently to hold the specimen together. 42 The time from the CPC powder-liquid mixing to this point was measured as the setting time.…”