Nanomedicine, Volume IIA: Biocompatibility

© 2003 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume IIA: Biocompatibility, Landes Bioscience, Georgetown, TX, 2003 Biocompatibility of Shape Memory Materials

Another interesting material of possible nanomedical relevance is Nitinol (an equiatomic alloy of nickel and titanium) and other shape memory effect (SME) alloys [1408, 1409] and polymers [5671] that are capable of temperature-driven reversible phase transformations. Some may allow thermal cycling between 30-50 oC [1419] at frequencies up to ~100 Hz [1419] and applied loads of ~3-6 x 108 N/m2 [1408, 1419]. TiNi alloys can be deformed below a martensite finish temperature but recover their initial shape when heated above a temperature corresponding to the austenite temperature [1409]. Grain phases are often a few microns in size [1409]. Grain sizes smaller than 100-200 nm inhibit SME in experiments on bulk materials [1410], and bulk-deposited TiNi films thinner than 100 nm apparently cannot readily transform to martensite [1411, 1412]. However, ~40 nm reaction layers have been studied [1413, 1414], and TiNi transitions are known to occur between a cubic austenite phase with lattice size c = 0.3015 nm [1415] and a monoclinic martensite phase with lattice sizes c = 0.4622 nm [1415] or c = 0.4646 nm [1416]. So it is not inconceivable that nanomanufactured Nitinol crystal having molecular-size grain structures placed with atomic precision could demonstrate SME near the nanometer scale. TiNi has already found uses in microrobotics [1417-1419]. Thin-film actuated TiNi microvalves have been successfully operated for up to 2 million cycles [1420] at 1% strain [1421] although long-term SME stability remains a concern [1408].

Nitinol has good biocompatibility [1422] and is as nontoxic as titanium [1423]. This good biocompatibility is believed to be due to the tendency of TiNi to develop a compact thin film of titanium dioxide upon exposure to air [1422, 1424], which largely [1425, 1426, 6165] prevents the cytotoxic Ni component from leaching out. One in vitro experiment [1424] tested TiNi particles < 5 microns in diameter on BHK-21 cells cultured in 10% infant calf serum. Naked metal particles induced obvious morphological transformation clones whereas TiO2-coated particles produced results not significantly different from negative controls. (Less than 1% internal oxygen impurity poisons the SME, however [1427].) TiNi is found in many medical applications including orthodontic tasks [1428], bone clamps [1429], bronchial prostheses [1430], and even eyeglass frames [1431]. The material has been investigated for intravascular therapy as a microgripper [1419] and as a means for controlled snakelike motion of small active catheters [1432] with expandable TiNi components that can be fed through the catheters to break up blood clots and prevent embolisms [1431]. Interestingly, one recently-discovered polymorph of titanium dioxide is the hardest known oxide [4744], and the biocompatibility of TiO2 particles has been investigated [4745-4747].

Porous Nitinol shows no adverse effects and shows good bone attachment and tissue ingrowth when implanted in rabbit tibias and back muscle for 3-12 weeks. TiNi demonstrates good healing of bone tissue and bone remodeling with osteoclastic and osteoblastic activity in the bone cortex [1433]. Porous TiNi implanted in rabbit cranial bone made bone contact with cranial hard tissue. This contacted bone has the same properties as surrounding cranial bone, suggesting that Nitinol is suitable for craniofacial applications [1434]. TiNi has good in vitro biocompatibility with human osteoblasts and fibroblasts [1426]. The material induces no toxic effects, no decrease in cell proliferation, and no inhibition of growth of cells in contact with the metal surface. Nitinol does not induce inhibition of mitosis in cultured human fibroblasts [1423]. Fibroblasts seeded on porous TiNi sheets grow into the holes, showing good cytocompatible behavior [1433]. TiNi implanted perineurally or in muscle is nontoxic and nonirritating in rat soft tissues over 2-26 weeks [1435], with low immune cell response and a modest inflammatory response similar to stainless steel and Ti-6Al-4V alloy [1435]. No necroses, granulomas, or signs of dystrophic soft tissue calcification were found. Only a few foreign-body giant cells were present with an encapsulating membrane about the same thickness as for stainless steel after 26 weeks [1435]. In vivo studies of Nitinol implanted for 3-17 months in beagles also showed no adverse tissue reactions from the implants [1425].


Last updated on 30 April 2004