Resorbable nanocomposites with bone-like strength and enhanced cellular activity

Abstract

Bone cements for treatment of fractures at weight-bearing sites are subjected to dynamic physiological loading from daily activities. An ideal bone cement rapidly sets after injection, exhibits bone-like strength, stimulates osteogenic differentiation of endogenous cells, and resorbs at a rate aligned with patient biology. However, currently available materials fall short of these targeted properties. Nanocrystalline hydroxyapatite (nHA) enhances osteogenic differentiation, new bone formation, and osteoclast differentiation activity compared to amorphous or micron-scale crystalline hydroxyapatite. However, the brittle mechanical properties of nHA precludes its use in treatment of weight-bearing bone defects. In this study, we report settable nHA-poly(ester urethane) (PEUR) nanocomposites synthesized from nHA, lysine triisocyanate (LTI), and poly(caprolactone) triol via a solvent-free process. The nanocomposites are easily mixed and injected using a double-barrel syringe, exhibit mechanical properties exceeding those of conventional bone cements, enhance mineralization of osteoprogenitor cells in vitro, and undergo osteoclast-mediated degradation in vitro. This combination of properties cannot be achieved using other technologies, which underscores the potential of nHA-PEUR nanocomposites as a new approach for promoting bone healing at weight-bearing sites.

Settable polymer/ceramic composite bone grafts stabilize weight-bearing tibial plateau slot defects and integrate with host bone in an ovine model

“…[27, 28] In a recent study, lysine triisocyanate (LTI) was grafted to nanocrystalline hydroxyapatite (nHA) particles and crosslinked with poly(ε-caprolactone) triol to create nHA-PEUR hybrid inorganic-organic polymers with bending and compressive strengths >90 MPa, which is sufficiently high to support structural repair of bone. [29] nHA-PEUR stimulated osteoid mineralization and exhibited osteoclast-mediated resorption in vitro [29] and in vivo . [30] These nHA-PEUR hybrid polymers are resistant to hydrolytic degradation (<2% mass loss after 4 months at 37¼C in vitro )[31, 32] but readily degrade in the presence of reactive oxygen species (ROS) secreted by infiltrating cells.…”

“…[29] nHA-PEUR stimulated osteoid mineralization and exhibited osteoclast-mediated resorption in vitro [29] and in vivo . [30] These nHA-PEUR hybrid polymers are resistant to hydrolytic degradation (<2% mass loss after 4 months at 37¼C in vitro )[31, 32] but readily degrade in the presence of reactive oxygen species (ROS) secreted by infiltrating cells. [32, 33] Thus, nHA-PEUR-derived bone cements are anticipated to provide mechanical stability as they remodel, since they undergo negligible degradation until cells infiltrate the cement.…”

“…[30] These nHA-PEUR hybrid polymers are resistant to hydrolytic degradation (<2% mass loss after 4 months at 37¼C in vitro )[31, 32] but readily degrade in the presence of reactive oxygen species (ROS) secreted by infiltrating cells. [32, 33] Thus, nHA-PEUR-derived bone cements are anticipated to provide mechanical stability as they remodel, since they undergo negligible degradation until cells infiltrate the cement. While these biomaterials meet the criteria of bone-like strength, stimulation of osteogenic differentiation, and resorption by osteoclasts, their ability to promote bone healing of weight-bearing fractures has not been previously investigated.…”

Polylactide Composite Pins Reinforced with Bioresorbable Continuous Glass Fibers Demonstrating Bone-like Apatite Formation and Spiral Delamination Degradation

“…Compared with pure HA of the same crystallinity, Mg-doped HA implant materials offer better adhesion and proliferation of osteoblast cells [36]. Therefore, a HA surface can layer presents superior osteoconductivity, can promote cellular function, and offers excellent biocompatibility [47,48]. The apatite layer deposited on the biocomposite pins investigated in this study had a lower Ca/P ratio than the stoichiometric HA (1.67) (Figure 5A,B), whereas the Ca/P ratio of the apatite layer deposited on the pure PLDLA was 1.82 (Figure 5C).…”

Fabrication of Trabecular Bone‐Templated Tissue‐Engineered Constructs by 3D Inkjet Printing

“…In this study, we used a templating approach in which 3D‐printed wax molds were filled with a reactive, flowable, and settable poly(ester urethane)‐nanocrystalline hydroxyapatite (PUR‐nHA) hybrid polymer with bone‐like strength. We have shown that this organic–inorganic hybrid polymer promotes osteoblast differentiation and mineralization, supports osteoclast‐mediated resorption, and remodels to form new bone in vivo …”