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

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

15.2.1.3 Bioactive Materials

When an artificial material is placed in the human body, tissue reacts to the implant in a variety of ways depending on the material type [241]. The mechanism of tissue attachment (if any) depends on the tissue response to the implant surface. Materials can generally be placed into three classes representing the type of tissue response they elicit: chemically inert, bioresorbable, or bioactive [238].

Chemically inert materials such as titanium [280-282], tantalum [282, 283], polyethylene [280, 284], and alumina (Al₂O₃) [285-289] exhibit minimal chemical interaction with adjacent tissue. However, even these substances are not entirely physically inert, as a “defensive” fibrous tissue capsule will normally form around chemically inert implants [238] in a reaction analogous to that of the body controlling tuberculosis by encapsulating the invading microorganisms. Tissue may also physically attach to these inert materials by tissue growth into surface irregularities, by bone cement, or by press-fitting into a defect. This morphological fixation is not ideal for the long-term stability of permanent implants and often becomes a problem with orthopedic and dental implant applications [238] in part due to a lack of strength. Nevertheless, many polymeric implant devices are generally regarded as safe and effective for periods of months to years. Biological attack occurs, but is compensated for in the design specifications [2538].

Bioresorbable materials such as tricalcium phosphate [289-292], polylactic-polyglycolic acid copolymers [292-294], and even some metals [4886, 4888], are designed to be slowly replaced by tissue (such as bone or skin). They are used in drug-delivery applications [246-248, 295, 296] or in biodegradable implantable structures such as sutures [4876-4880], suture anchors [4881-4883], meniscus arrows [4884], stents [4886-4891] and other devices [4885]. STAR Inc., a startup founded in the year 2000 by Benjamin Chu and others at the State University of New York, Stony Brook, manufactures an electrospun nanofiber polymer-mesh membrane designed to prevent body tissues from sticking together as they heal, and to break down in the body over time like biodegradable sutures. Anti-adhesion materials made of cellulose or hyaluronan are already available from Johnson & Johnson and Genzyme Corp., but doctors are unsatisfied with these materials because they tend to stick to a surgeon’s wet glove and don’t always work well inside a patient. Chu claims that STAR’s nanomesh, using ~150 nm-diameter nanofibers, is more flexible, easier to hold, and may also be able to deliver antibiotics, painkillers or other medicines directly, and in smaller quantities, to internal tissues [4874]. eSpin Technologies [4875] is also commercializing nanofibers made of organic and biological polymers [4874].

Bioactive materials include certain glasses [297], ceramics, glass-ceramics [297], and plasma-sprayed hydroxyapatites [288] that contain oxides of silicon, sodium, calcium, and phosphorus (SiO₂, Na₂O, CaO, and P₂O₅) and that constitute the only materials known to form a chemical bond with bone, resulting in a strong mechanical implant-bone bond [298]. These materials are referred to as bioactive [299-301] because they bond to bone (and in some cases to soft tissue) through a time-dependent, kinetic modification of the surface triggered by their implantation within living bone. In particular, an ion-exchange reaction takes place between the bioactive implant and surrounding body fluids during which chemical species from the ceramic diffuse into the fluid and vice versa, resulting, over time, in the formation of chemically graded layers that become a biologically active hydrocarbonate apatite (calcium phosphate) layer on the implant that is chemically and crystallographically equivalent to the mineral phase in bone, producing a relatively strong interfacial bonding [238]. Although bioactive materials would appear to be the answer to biomedical implant fixation problems, available bioactive glasses (i.e., Bioglass [302-304]) are not suitable for load-bearing applications, and so are not used in orthopedic implants. In fact, their use for other implants, even some dental applications, is limited because they have a low resistance to crack growth.

However, there are stronger ceramic materials, crystalline in structure, that are not as bioactive. Ion beam surface modification has been used to alter the atomic structure and chemistry at the surface of these crystalline ceramics to improve bioactivity, allowing ion-exchange in the modified material upon implantation [238]. For example, Richard France at the University of Sheffield has studied the effect of surface chemistry on the attachment of human skin cells (keratinocytes) from the epidermis. He uses a technique known as plasma polymerization to make surfaces containing specific concentrations of a particular functional group [897]. France finds that keratinocytes prefer a specific concentration (about 3%) of carboxylic acid functional groups. Such a surface promotes cell attachment as well as collagen deposition, and collagen is the keratinocytes’ natural substratum at the dermal-epidermal junction. The cells also prefer high concentrations of amine or alcohol groups, although on these surfaces the attachment rarely matches that obtained on collagen. These plasma polymers support cell growth over a number of days and in the year 2000 were being developed as a transfer dressing to allow cells to be cultured and subsequently applied to wound beds such as burns or ulcers, promoting healing [897].

Adam Curtis and colleagues at the University of Edinburgh have studied the effects of implant surface topography using various etched substrata. Cells align themselves to micron-scale features on a titanium surface, and the size and shape of features can control the behavior of different cells (Section 15.2.2.3). For instance, fibroblasts (responsible for new collagen fiber deposition during wound healing) migrate along the micron-sized grooves, while macrophages (white blood cells responsible for digesting foreign matter) can become trapped within these features [897]. Biomaterial scientists can exploit such topographical controls to provide new ways to guide regeneration and healing [897].

Note that in many nanomedical applications, tissue integration with the implant is desirable (Section 15.2.2.2), and may involve chemical interaction and host cell adhesion with a bioactive implant surface. For other applications such as hemodynamic systems, a nonadhesive inert nanodevice surface is desirable (Section 15.2.2.1) to prevent thrombus formation or nidus of infection [306]. In other words, appropriate biocompatibility is very application-specific.

Last updated on 30 April 2004