Strategies to Improve Bone Healing: Innovative Surgical Implants Meet Nano-/Micro-Topography of Bone Scaffolds

Abstract

Successful fracture healing is dependent on an optimal mechanical and biological environment at the fracture site. Disturbances in fracture healing (non-union) or even critical size bone defects, where void volume is larger than the self-healing capacity of bone tissue, are great challenges for orthopedic surgeons. To address these challenges, new surgical implant concepts have been recently developed to optimize mechanical conditions. First, this review article discusses the mechanical environment on bone and fracture healing. In this context, a new implant concept, variable fixation technology, is introduced. This implant has the unique ability to change its mechanical properties from “rigid” to “dynamic” over the time of fracture healing. This leads to increased callus formation, a more homogeneous callus distribution and thus improved fracture healing. Second, recent advances in the nano- and micro-topography of bone scaffolds for guiding osteoinduction will be reviewed, particularly emphasizing the mimicry of natural bone. We summarize that an optimal scaffold should comprise micropores of 50–150 µm diameter allowing vascularization and migration of stem cells as well as nanotopographical osteoinductive cues, preferably pores of 30 nm diameter. Next to osteoinduction, such nano- and micro-topographical cues may also reduce inflammation and possess an antibacterial activity to further promote bone regeneration.

Promoting bone callus formation by taking advantage of the time-dependent fracture gap strain modulation

“…The fracture of the bone disrupts the local vascularity and triggers the inflammatory cascade. During this first, inflammatory phase, the secretion of mediators into the fracture hematoma regulates the differentiation of mesenchymal stem cells into osteoblasts, fibroblasts and chondrocytes as well as cell infiltration and angiogenesis ( 45 ). In the subsequent fibrovascular phase, the non-perfused bone fragments are resorbed.…”

Tuning foreign body response with tailor-engineered nanoscale surface modifications: fundamentals to clinical applications

“…Human MSCs were induced to differentiate into osteoblast-like cells by the outermost titanium oxide nanopit layers ranging from 70 to 100 nm, whereas narrower 30 nm nanopits promoted cell attachment without differentiation. 99 During bone remodeling and absorption, osteoclasts form 40 m-diameter pits in the seal zone while breaking down older bone tissue, demonstrating that nanopit topographical characteristics are essential in determining osteogenesis. Changing the parameters of nanopit topographies (pit diameter and depth) drastically altered the behaviors of bone-forming cells, with osteogenic differentiation improved under appropriate nanopit topologies.…”

Effects of rmBMP-7 on Osteoblastic Cells Grown on a Nanostructured Titanium Surface

“…Over the past two decades, the development of osseointegrated implant surfaces has established their structuring at the micron scale as a fundamental modification for stimulating bone deposition in direct contact with the implant. Furthermore, nanoscale surface modifications have also been applied due to their known beneficial effects on bone cells and tissue repair [ 14 , 15 ]. For example, the surface nanotopography of titanium (Nano-Ti), created by a chemical treatment based on sulfuric acid (H 2 SO 4 ) and hydrogen peroxide (H 2 O 2 ), stimulates the initial secretion of bone sialoprotein (BSP) and osteopontin (OPN)—two important osteoblast markers—and promotes increased mineralized matrix formation in vitro and in vivo [ 16 , 17 , 18 ], an effect that involves the activation of the BMP-2 and α1β1 integrin signaling pathways [ 12 , 19 , 20 ].…”