Photothermal stress triggered by near infrared-irradiated carbon nanotubes promotes bone deposition in rat calvarial defects

Abstract

The bone regenerative healing process is often prolonged, with a high risk of infection particularly in elderly and diseased patients. A reduction in healing process time usually requires mechanical stress devices, chemical cues, or laser/thermal therapies. Although these approaches have been used extensively for the reduction of bone healing time, the exact mechanisms involved in thermal stress-induced bone regeneration remain unclear. In this study, we investigated the effect of optimal hyperthermia on rat calvarial defects in vivo and on osteogenesis in vitro. Photothermal stress stimulation was carried out using a new photothermal device, composed of an alginate gel including in carbon nanotubes and their irradiator with near-infrared light. Photothermal stress (15 min at 42℃, every day), trigged by near-infrared-induced carbon nanotube, promoted bone deposition in critical-sized calvarial defects compared with nonthermal stress controls. We recently reported that our novel DNA/protamine complex scaffold induces bone regeneration in calvarial defects. In this study, photothermal stress upregulated bone deposition in DNA/protamine-engrafted calvarial defects. Furthermore, photothermal stress significantly induced expression of osteogenic related genes in a time-dependent manner, including alkaline phosphatase, osterix, and osteocalcin. This was observed in DNA/protamine cells, which were expanded from regenerated tissue engrafted into the DNA/protamine scaffold, as well as in human MG63 preosteoblasts. In summary, this novel carbon nanotube-based photothermal stress approach upregulated expression of osteogenic-related genes in preosteoblasts, resulting in promotion of mineral deposition for enhanced bone repair.

Bioinspired extracellular vesicles embedded with black phosphorus for molecular recognition-guided biomineralization

“…20). NIR irradiation significantly up-regulated the expression of HSP 70 in Apt-bioinspired MVs cultured osteoblasts, which can be ascribed to the good photothermal performance of the BPQDs in Apt-bioinspired MVs 25–29 . Taken together, the above results confirm that the Apt-bioinspired MVs with photothermal effect can promote biomineralization and the expression of proteins, such as ALP, Runx2, and HSP 70 plays essential roles in the biomineralization process.…”

“…Furthermore, ultrasmall BP nanosheets with sizes of several nanometers (usually named as BP quantum dots, BPQDs) have high photothermal conversion efficiency and thus can be used as a promising photothermal agent 24 . Previous researches have indicated that hyperthermia promotes biomineralization by stimulating the up-regulated expression of proteins, including alkaline phosphatase (ALP) and heat shock proteins (HSP) 25–29 , thus increasing the generation of mineral crystals and realizing bone reconstruction 29–31 . These special properties render BPQDs promising biomaterials for stimulating biomineralization and further promoting mineralization-guided biological behavior regulation and medical engineering.…”

<p>Advanced Black Phosphorus Nanomaterials for Bone Regeneration</p>

“…Previous researches have demonstrated that mild localized heat can efficiently stimulate cell proliferation and induce rapid in situ bone regeneration in vivo. [102][103][104] BP nanomaterials have high photothermal conversion efficiency. This property of BP nanomaterials can be used for both antitumor and tissue regeneration applications.…”

Black phosphorus-based 2D materials for bone therapy

“…Compared with HA, the advantages of BP are as follows: 1) BP can be degraded into non-toxic phosphate after oxidation, then attract surrounding free calcium ions and combine into calcium phosphate mineralization and deposition to promote in-situ bone regeneration and repair [ 128 ]; 2) Due to the strong light absorption ability of BP in the NIR region, BP-based nanomaterials have a stable, damage-free light-controlled adjustment release mode, which makes the release of loaded drugs more stable and longer-lasting [ 49 ]; 3) In addition, there have been numerous studies showing that BP has good capability of photothermal conversion under NIR region and local hyperthermia treatment has also been confirmed to up-regulate alkaline phosphatase (ALP) [ 129 , 130 ], heat shock protein (HSP) [ 131 ], to increase the formation of mineralized crystal, and to achieve longitudinal and concentric growth of bone, thereby accelerating the process of bone repair [ 132 , 133 ]. ALP is the main marker that reflects bone metabolic capacity and its level is related to the differentiation of osteoblasts and greatly affects the process of osteoblast cell matrix mineralization [ 134 ].…”