Specific Biomimetic Hydroxyapatite Nanotopographies Enhance Osteoblastic Differentiation and Bone Graft Osteointegration

Abstract

Impaired healing of cortical bone grafts represents a significant clinical problem. Cadaveric bone grafts undergo extensive chemical processing to decrease the risk of disease transmission; however, these processing techniques alter the bone surface and decrease the osteogenic potential of cells at the healing site. Extensive work has been done to optimize the surface of bone grafts, and hydroxyapatite (HAP) and nanotopography both increase osteoblastic differentiation. HAP is the main mineral component of bone and can enhance osteoblastic differentiation and bone implant healing in vivo, while nanotopography can enhance osteoblastic differentiation, adhesion, and proliferation. This is the first study to test the combined effects of HAP and nanotopographies on bone graft healing. With the goal of identifying the optimized surface features to improve bone graft healing, we tested the hypothesis that HAP-based nanotopographic resurfacing of bone grafts improves integration of cortical bone grafts by enhancing osteoblastic differentiation. Here we show that osteoblastic cells cultured on processed bones coated with specific-scale (50-60 nm) HAP nanotopographies display increased osteoblastic differentiation compared to cells on uncoated bone, bones coated with poly-l-lactic acid nanotopographies, or other HAP nanotopographies. Further, bone grafts coated with 50-60-nm HAP exhibited increased formation of new bone and improved healing, with mechanical properties equivalent to live autografts. These data indicate the potential for specific HAP nanotopographies to not only increase osteoblastic differentiation but also improve bone graft incorporation, which could significantly increase patient quality of life after traumatic bone injuries or resection of an osteosarcoma.

3D Printing of Personalized Artificial Bone Scaffolds

“…The 25 -30 nm coating had primary islands (900 nm in diameter), and the 50 -60 nm coatings had secondary islands (200 nm in diameter) in addition to primary islands, while the 100 -120 nm coating displayed tertiary islands (40 nm in diameter). 46 However, the trough -to -crest heights of these different nanotopographies were not significantly different. These studies suggest that these specific fractal patterns, and not the trough -to -crest heights, of the nanotopographies enhance osteoblastic differentiation and osteogenic potential.…”

“…44,45 Similar features were associated with improved healing of a critical -sized defect in vivo. 46 Therefore, it may be advantageous to replicate in scaffolds the nanotopographical features of bone ' s native surface. However, scaffolds with nanotopographical features require higher spatial resolution than current 3DP can generally provide.…”

“…This approach is based on previous work showing that specific nanotopographies (60 -80 nm but not 15 -25 or over 100 nm), fabricated from HA, increase adhesion, proliferation, and osteoblastic differentiation of mesenchymal stem cells. 46 These nanotopographies refer to a mixed and variable topography, containing bumps, islands, and fractal patterns, as shown in Figure 2. The 25 -30 nm coating had primary islands (900 nm in diameter), and the 50 -60 nm coatings had secondary islands (200 nm in diameter) in addition to primary islands, while the 100 -120 nm coating displayed tertiary islands (40 nm in diameter).…”

In vivo bone tunnel evaluation of nanoparticle‐grafts using an ACL reconstruction rabbit model

“…In a study by Loiselle et al . bone grafts coated with 50–60 nm nano‐HAp exhibited increased bone formation, healing, osteoblast differentiation, and osseointegration …”

“…33,34 In a study by Loiselle et al bone grafts coated with 50-60 nm nano-HAp exhibited increased bone formation, healing, osteoblast differentiation, and osseointegration. 35 The aim of the study is to investigate the remodeling outcomes of grafts derived from acellular human gracilis tendon grafts conjugated with AuNP and nano-HAp. The ACL was reconstructed in 11 New Zealand rabbits using grafts conjugated without nanoparticles, with 20 nm AuNP, and with 20 nm 1 nano-HAp.…”