Porous ceramics of hydroxyapatite was fabricated utilizing the crystal growth of thin ice columns parallel to one another in gelatin gel containing hydroxyapatite nanoparticles. The obtained ceramics possessed unidirectional pore channels with a porosity of around 75% and showed compressive strength of up to 13.1 MPa. As control materials, porous hydroxyapatite ceramics with a directionless pore structure were also fabricated by isotropic freezing and compared with the unidirectional samples regarding compressive strength and tissue reaction in vivo. Although the porosity and pore size distribution were similar, the compressive strength and new bone formation ability of the unidirectional samples were significantly greater than those of the random structured porous ceramics.

The organic acid-based crosslinkers trisuccinimidyl citrate (TSC), disuccinimidyl malate (DSM), and disuccinimidyl tartarate (DST) were combined with human serum albumin (HSA) to produce biodegradable solid— liquid-type adhesives, TSC-A, DSM-A, and DST-A. The bonding time of TSC-A, DSM-A, and DST-A was 15, 10, and 5 min, respectively, when the content of organic acid-based crosslinkers was 0.5 mmol and the HSA concentration was 44 w/v%. Five minutes after application of the adhesives, the DST-A adhesive had the greatest bonding strength (489.14 ± 93.06 kPa) compared with TSC-A (120.86 ± 73.83 kPa) and DSM-A (224.44 ± 79.53 kPa). The bonding strength of DSM-A and DST-A increased with increasing DSM or DST content up to 0.5 mmol, after that the bonding strength decreased. While, the bonding strength of the TSC-A adhesive was relatively low at any TSC content compared with the other adhesives. The bonding strength of DST-A with 0.3 mmol of DST increased with increasing HSA concentration up to 44 w/v%, and then decreased. The bonding strength of the DST-A adhesive was 3.2-fold greater than that of a commercial aldehyde-based adhesive and 6-fold greater than that of a fibrin-based adhesive. DST-A has excellent biocompatibility, bioabsorbability, and only mild tissue reaction in rat subcutaneous tissues.

A novel glue consisting of human serum albumin (HSA) and citric acid derivative (CAD) was developed where the glue is named as CAD-A glue. In this adhesive, CAD works as a crosslinking reagent of HSA. For preparing crosslinking reagent CAD, using citric acid as a starting material, three carboxyl groups of a citric acid were modified with N-hydroxysuccinimide in the presence of 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride. From 1H-NMR spectrum, CAD with three active ester groups in a molecule was successfully synthesized with a high yield (more than 80%). The boding time of CAD-A glue to collagen-based casing was saturated within 15 minutes. The bonding strength of this glue to collagen-based casings increased with increasing of HSA concentration. The maximum bonding strength of CAD-A glue was a slightly low level compared to the bonding strength of cyanoacrylate adhesive and was 9 times higher than that of fibrin glue. The CAD-A glue showed excellent biocompatibility and high ability of wound closure similar to that of cyanoacrylate-based adhesive when glues were applied to the mouse skin. These results suggested that this developed adhesive had both tissue compatibility and bonding strength for use in clinical field.

Unidirectional porous hydroxyapatite (UDPHAp) is an artificial bone substitute with a unique microstructure consisting of 100–300-µm oval pores that present the material unidirectionally. UDPHAp has a compression strength of 14 MPa and a porosity of 75%, which promotes cell migration and capillary formation within the material. Despite these advantageous properties, bone remodeling and bone formation with UDPHAp remain unclear. To examine long-term remodeling and differences in bone formation based on the defect site, trapezoidal prism-shaped UDPHAp blocks were implanted into rectangular-shaped cortical bone defects in the proximal tibia of Japanese white rabbits. Histological analysis performed at 52 and 104 weeks after implantation revealed that bone and capillaries had formed within the implanted UDPHAp material. Bone formed within the UDPHAp implanted in the cortical defect of rabbit tibia and remodel up to two years. The percentage of new bone area within UDPHAp was larger in cortical lesions than that in medullary lesions. These findings suggest that UDPHAp is a promising material for the repair of non-critical-sized cortical bone defects.