Materials science breakthroughs are making it possible
to precisely program the properties of biomaterials to make them
'bioactive.'
The use of foreign materials in the human body has an
impressively long history. In approximately 600 A.D, the Mayans
used mother of pearl to fashion dental implants that apparently
integrated with bone. An iron dental implant dating back to 200
A.D. has been found in Europe. The use of sutures has an even
longer history, stretching back some 32,000 years. Fastforwarding
through the centuries, elephant ivory was used to fashion the first
documented hip implant in 1891.
Most biomaterials used over the course of history were intended
to be biopassive-simply tolerated by the body. This is beginning to
change, however, as there is increasing demand to create
biomaterials that support the field of regenerative medicine. In
the meantime, inert biomaterials are also continuing to evolve.
Three Generations of Biomaterials
DSM
Biomedical (Berkeley, CA; www.dsm.com) classifes
inert biomaterials, which include everything from nitinol to
ceramics, as the first generation of biomaterials. Such materials
have traditionally been selected based on their physical
properties, which should closely approximate the tissue they are
meant to replace. They have also been selected for the degree to
which they are biopassive and nontoxic. "In orthopedics, this type
of first-generation-biomaterials thinking is best seen in total
artificial joints," says William Fuller, director of business
development at DSM Biomedical. "Knee and hip replacements stand out
as clinical successes, since there are over one million performed
annually, resulting in improved quality of life and a return to a
more active lifestyle for many patients."
There continues to be innovation among such first generation
biomaterials, Fuller says, pointing to DSM's Dyneema Purity fibers
as an example. Described by the company as the "world's strongest
medical fiber," Dyneema Purity is being applied to cardiovascular
applications such as reinforcing vascular balloon catheters. The
applications of the material in the orthopedic device market is
growing as well, where it appears in high-strength sutures used in
rotator cuff repairs, fixation devices for ACL repair, and spine
devices ranging from annulus repair to total disc replacement. The
company foresees expanded use of the material in ligament
fixations, in which the material's very low stretch results in a
rigid fixation that can improve the chance of rapidly readhering
torn ligaments to the bone.
"Ultra-high-molecular-weight polyethylene (UHMWPE) fibers are
helping to move implants beyond the limitations of more-traditional
orthopedic fibers and sutures," Fuller remarks. "Conventional
fibers such as polyesters, polypropylene, or nylon have moderate
strength and show a fairly large stretch (elongation) before they
ultimately break. The UHMWPE fibers are the opposite: Their
strength is much higher. On a weight basis, the fibers are more
than 10 times stronger than steel, and a braid or suture made from
these fibers has the potential to be twice as strong as a
comparable polyester product." Elongation is practically
imperceptible for this material, he adds. "When these fibers reach
breaking strength, elongation is approximately 3%. These
characteristics enable the design of novel, smaller medical
devices."
Innovation is also apparent in the use of materials that have a
long history of use as biomaterials, comments Robert Torgerson,
founder and president of RxFiber LLC(Windsor, CA ; www.rxfiber.com). Take
polyester, for example. "Companies developing next generation
devices using polyester yarns and other biomaterials are looking at
reducing the profiles of the devices," he explains. "Open surgical
procedures were the norm for endovascular and vascular procedures.
Now, heart valves, endovascular devices, stents, and so forth are
implanted via a catheter-based system. The diameters of these
delivery systems are large based on the device that needs to be
delivered. This system needs to pass through an orifice, such as a
femoral artery, iliac artery, or brachial artery." While this
demand puts stress on the orifice, various coatings have been
developed for the delivery systems to reduce this stress. "The
devices are limited to particular patients that can withstand the
diameter of the delivery system," Torgerson says. "A good portion
of patients have small-diameter anatomies, which require
smaller-diameter delivery systems. That, in turn, requires a
minimal amount of biomaterials going into the delivery system to be
delivered to the site."
Transcatheter endovascular devices are examples of such systems.
These products now use fairly large diameter yarns in the 40-denier
range requiring 20F or larger delivery systems, Torgerson notes.
"To reduce the profile and maintain the integrity of the device,
smaller, stronger yarns need to be developed to reduce the profile.
This has led to high-tenacity polyester yarns measuring 20 denier
or less with fewer filaments. This thickness maintains the
integrity of the device." RxFiber has developed small-denier, high
tenacity polyester yarns for such applications.
The Second Generation and Beyond
The second generation of biomaterials do more than simply aim to
go unnoticed in the body. They are formulated to incorporate
bioactive components, eliciting controlled actions and reactions in
a physiological environment. "Prominent examples of these
'bioactive' biomaterials in the orthopedic space include injectable
or implantable synthetic bone graft substitutes," Fuller
explains.
Third-generation biomaterials, which are designed based on an
expanded understanding of biology, aim to help achieve regeneration
as opposed to repair. "Third-generation biomaterials are being
designed to stimulate specific cellular responses at the molecular
level," Fuller explains. "In the orthopedics space, use of
bone-growth factors and platelet-rich plasma therapies signal the
beginning of a larger movement toward regenerative materials that
help the body heal itself. Related contemporary understanding of
the molecular and cell biology of tissue healing is incorporated
into materials design." Molecular modifications of polymer systems
elicit specific interactions with cell surface integrins and direct
cell proliferation, differentiation, and extracellular matrix
production and organization, Fuller adds. "These third generation
'bio-interactive' biomaterials stimulate regeneration of living
tissues. As for biocompatibility, these materials not only focus on
doing no harm but are also designed as elements of the treatment
itself."
Regeneration: Wave of the Future
Peter D. Gabriele, vice president, emerging technology at Secant Medical
Inc. (Perkasie, PA; secantmedical.com) has a similar view of
the future of biomaterials-stressing the importance of their use in
regenerative medicine. "For the future of biomaterials to move
forward, we must fully understand their consequence in the human
body," he says. "Materials are not inert, and we must be smarter in
making the connection between materials of construction and tissue
response." Gabriele explains that the potential for biomaterials in
regenerative medicine lies in developing an appropriate construct
that restores an organ system back to its natural function.
"Within this context, we are dealing with two immune systems at
the point of implant: the inflammatory system (the initial healing
process) and the adaptive immune system (the long-term system of
healing and function)," Gabriele notes. Thus, it is important to
know how a material affects the immune system, the healing process,
and the organ undergoing regeneration. "This intelligent design
movement involves finding the compliance match not only to the
material engineering properties but also to material biology,
bioactivity, and biocompatibility."
Related to this trend is an uptick in R&D efforts to develop
new biodegradable materials, such as polylactic acid. Capable of
dissolving into lactic acid, this material can be programmed to
provide structure to implants for a period of time ranging from six
months to two years.
"The next-generation biodegradable polymer offers several
advantages," Gabriele explains. "First, it distinguishes itself as
being designable (the compliance-matching criteria can be designed
in). Second, its breakdown products are metabolites, which means it
doesn't produce waste that must be flushed out of the body. And
finally, it is not antagonistic; it doesn't stimulate the immune
system to form scar tissue."
Existing materials have a narrow window of product development
capabilities, Gabriele notes. "However, the future biopolymer has a
much broader window, without diminishing such benefits as
compatibility and nonimmunogenic response," he adds. This single
material, depending on how it is processed, will have multiple
application areas. Within soft-tissue engineering, it holds the
potential for use in myocardial patches, engineered blood vessels,
scaffolds for cartilage restoration or retinal repair, and nerve
conduits. It could also be formulated into a composite for
orthopedic repair or a coating that creates a functional surface
for a material.
While regenerative medicine has an exciting future, the cost of
organ regeneration as the next generation of devices and
biomaterials is developed should not be overlooked, remarks
Torgerson from RxFiber. "This will be an extremely expensive
undertaking, and there is also the time involved with the
regeneration to recreate the organ of choice." However,
biomaterials will still be needed to create devices for emergency
situations, low-income cases, and other circumstances. "I am unsure
how an aorta may be regenerated and replaced without being an open
surgical procedure, he explains." But open procedures are
inherently risky and potentially fatal for some patients. A
transcatheter-based system using a device made of biomaterials
could save time and possibly even the patient's life. "We need to
continue our progress with developing next generation devices using
current and next-generation biomaterials," he concludes.
Source:
http://www.qmed.com/mpmn/article/biomaterials-step-21st-century?goback=%2Egmp_5097745%2Egde_5097745_member_256700631
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