Effect of Nitroglycerin Hydrogel on Repairing Critical Bone Defects

Due to their osteoconductive, osteoinductive, and osteogenic qualities, autologous bone grafts are the gold standard for augmenting bone, (1). However, problems, insufficient bone quantity, and/ or quality at the donor location could prevent it from being used. Consequently, a variety of bone graft materials, such as allografts and/or xenografts, were developed to improve bone development and provide an osteoconductive matrix in the so-called hard tissue critical-size defect (CSD) (2).

"critically-sized" defect is regarded as one that would not heal spontaneously despite surgical stabilization and requires further surgical intervention (3). The management of critical-sized bone defects remains a major clinical orthopedic challenge. Critical-sized bone defects are technically defined as those that will not heal spontaneously during the patient's lifetime. Bone loss greater than 2 times the diameter of the long bone diaphysis is unlikely to result in union despite appropriate stabilization methods (4).

Nitroglycerin, also known as glyceryl trinitrate (GTN), is a medication commonly used to treat heart conditions like angina pectoris and chronic heart failure. It acts as a potent vasodilator, dilating the vascular system to improve blood flow. Nitroglycerin has been found to have a positive effect on bone formation. Studies indicate that Nitroglycerin when applied topically, can increase bone formation and reduce bone resorption. This effect is achieved through the stimulation of osteoblastic differentiation and proliferation (5).

The mechanism of action of Nitroglycerin in bone formation involves its conversion into nitric oxide (NO), which plays a crucial role in stimulating bone formation. Nitric oxide released from nitroglycerin acts as a signaling molecule that enhances osteoblastic differentiation and proliferation of bone marrow-derived mesenchymal stem cells. This process leads to increased bone mineral density, improved bone geometry, and enhanced bone strength (5).

Hydrogels are natural or synthetic biocompatible polymers that are widely used in periodontal tissue engineering as a delivery material for different biologics (6). Synthetic hydrogels have superiority in chemical and mechanical properties over natural hydrogels (7). Carbopol or polyacrylic acid (PAA) is one of the most widely used polymers as a hydrogel. It is an anionic polyelectrolyte that can be readily polymerized and crosslinked to form hydrogels with a swelling capacity greater than their dry weight (8).