Angiogenesis is considered an important issue in the development of biomaterials for the successful regeneration of tissues including bone. While growth factors are commonly used with biomaterials to promote angiogenesis, some ions released from biomaterials can also contribute to angiogenic events. Many silica-based biomaterials have been widely used for the repair and regeneration of tissues, mainly hard tissues such as bone and tooth structure. They have shown excellent performance in bone formation by stimulating angiogenesis. The release of silicate and others (Co and Cu ions) has therefore been implicated to play critical roles in the angiogenesis process. In this short review, we highlight the in vitro and in vivo findings of angiogenesis (and the related bone formation) stimulated by the various types of silicon-containing biomaterials where silicate ions released might play essential roles. We discuss further the possible molecular mechanisms underlying in the ion-induced angiogenic events.
Inorganic bioactive nanomaterials are attractive for hard tissue regeneration, including nanocomponents for bone replacement composites and nanovehicles for delivering therapeutics. Bioactive glass nanoparticles (BGn) have recently gained potential usefulness as bone and tooth regeneratives. Here we demonstrate the capacity of the BGn with mesopores to load and deliver therapeutic molecules (drugs and particularly genes). Spherical BGn with sizes of 80–90 nm were produced to obtain 3–5 nm sized mesopores through a sono-reacted sol–gel process. A simulated body fluid test of the mesoporous BGn confirmed their excellent apatite forming ability and the cellular toxicity study demonstrated their good cell viability up to 100 μg ml−1. Small molecules like chemical drug (Na-ampicillin) and gene (small interfering RNA; siRNA) were introduced as model drugs considering the mesopore size of the nanoparticles. Moreover, amine-functionalization allowed switchable surface charge property of the BGn (from −20–30 mV to +20–30 mV). Loading of ampicillin or siRNA saturated within a few hours (∼2 h) and reflected the mesopore structure. While the ampicillin released relatively rapidly (∼12 h), the siRNA continued to release up to 3 days with almost zero-order kinetics. The siRNA–nanoparticles were easily taken up by the cells, with a transfection efficiency as high as ∼80%. The silencing effect of siRNA delivered from the BGn, as examined by using bcl-2 model gene, showed dramatic down-regulation (∼15% of control), suggesting the potential use of BGn as a new class of nanovehicles for genes. This, in conjunction with other attractive properties, including size- and mesopore-related high surface area and pore volume, tunable surface chemistry, apatite-forming ability, good cell viability and the possible ion-related stimulatory effects, will potentiate the usefulness of the BGn in hard tissue regeneration.
22 December 2014 in ACS Applied Materials & Interfaces