Micro and Nanotechnology and the Aging Spine

Lisa A. Ferrara

INTRODUCTION

In the United States by the year 2000, approximately 20% of all Americans were older than 65. Twelve percent were older than 85. With an aging population, a higher proportion of the elderly seek orthopedic treatment, due to the prevalence of musculoskeletal complaints. Currently, 25% of orthopedic patients are 65 and older. The Census Bureau projects that the 65 and older population will double from 33 million to 65 million by 2030, while the younger age groups will remain the same. Physicians will be faced with a greater number of individuals who are experiencing intellectual failure, immobility, instability, incontinence, insomnia, degenerative musculo-skeletal disorders, and iatrogenic problems.

The aging process presents a cascade of events that affect the health of the musculoskeletal system, in particular, the human spine. The maximum bone mineral density of an individual is reached between the ages of 18 to 20 years of age. As aging progresses, muscle size and strength begin to decrease, by as early as age 25. Accompanying these changes are reductions in hormone levels for both men and women, contributing to a decline in bone density and muscular strength. As we age, the musculoskeletal system experiences degenerative changes resulting in fibrosis, stiffening, and shrinkage of the soft tissue; bone loss; joint changes; and tissue desiccation due to a reduction in proteoglycans and a change in collagen type (i.e., intervertebral disc).10 With respect to the aging spine, this fibrosis and stiffening reduces the osmotic properties of the disc and the ability of the disc to obtain and/ or maintain vital nutrients while eliminating noxious wastes. Disc desiccation initiates a cascade of progressive degenerative events leading to loss of disc height, degenerative facets, and compression of the neural structures resulting in pain. The degenerative process continues as the discs of the spine undergo these arthritic bony changes, resulting in altered loading patterns on the spine, further enhancing the patient's pain and neurological deficits.

As a result, the elder population suffers from a variety of degenerative disorders afflicting the spine, such as osteoporosis, degenerative disc disease, compromised facet joints, spondylotic myelopathies, and stenosis, all resulting in pain and loss of motion. However, the longer life expectancies and increased levels of activity at a much later stage in life place greater demands on the spine and musculoskeletal system. Over the last decade, there has been a surge in orthopedic implant development and spinal arthroplasty devices to preserve or restore long-term joint motion.

As the overall life expectancy continues to increase worldwide, the need for improved medical care increases and is expected to continue as the baby boom generation crosses into the senior phase of their lives. With continued development of novel medical technologies and a changing health care environment, microinvasive technological advancements in medicine continue to progress, especially within the orthopedic and neurosurgical arena, where a new generation of medicine is evolving.

Smart technology or "smart systems" are terms used to define systems that are capable of imitating human intelligence. A smart system with respect to medical devices is a system that can automatically sense and respond to a changing environment once implanted into the human body. Smart technologies employ smart microsensors that can sense minuscule changes in pH, chemistry, stress, strain, pressures, and temperatures; smart materials that change their properties in response to a particular stimulus; microelec-tromechanical technologies that can sense and respond at the cellular level; and nanoelectromechanical technologies that behave at the molecular level.

With respect to the aging spine, the ability to sense adverse changes in vivo and manipulate cells and molecules presents the possibility of promising treatments for debilitating diseases and musculoskeletal disorders. Smart materials that have the ability to repair and reorganize human tissue and eventually allow for an engineered material and scaffold to be substituted by newly regenerated tissue provide an attractive solution for implant and tissue longevity. Such novel materials should be capable of nonlinear responses to imitate the mechanics of living tissue. Smart biosensors and tooling can lend to improved surgical techniques and patient outcomes. The incorporation of micro- or nanotechnology into spinal implants and surgical tooling can enhance surgical accuracy; provide precision cutting techniques for microsurgery with minuscule tissue damage; manipulate cellular and subcellular structures; develop genetic engineering clinical strategies; monitor and respond to tissue-targeting feedback; and create biosensors that can provide the surgeon with real-time, continuous biofeedback with respect to implant performance during the lifespan of the applied treatment. Smart materials with preprogrammed porosities can function as biological sieves for implantable drug delivery systems, controlled differentiated tissue growth, and disease barriers. Finally, ultra-small tweezers that are of nanosize allow for manipulation of molecules to change the course of a disease.

The areas in which such interventions may become clinically applicable in the aging spine include nuclear regeneration and replacement technologies, neural regeneration, localized delivery of pharmaceuticals such as bone morphogenetic proteins for localized and controlled bone growth, delivery of antibiotics and pain medications for long-term steady-state delivery, and monitoring of implant lifespan. Nucleus regeneration may involve the employment of semipermeable membranes that allow specific cells or humoral agents to pass into a disc space that spur and nurture the regeneration process. Neural regeneration techniques must not only overcome the humoral stimulation barriers required to induce regeneration, they must overcome physical barriers and the complexity of the nervous system involving complex synaptic connections that are poorly understood. MEMS/ NEMS and polymer technologies can be utilized to create textured surfaces that facilitate neural growth, while grids and tubes that can be electrically stimulated can be used for orienting neuronal growth.

SPINAL ETIOLOGIES121321

Degenerative Disc and Congenital Disorders

The normal aging process results in degenerative disorders due to normal wear and tear of the joints and soft tissues. Although the process of aging results in disc desiccation, facet degeneration, osteophyte formation, and a cascade of mechanical and chemical events that lead to degenerative conditions that cause pain and neurological changes, the ability of the body to heal the tissues still occurs, although at a slower rate with progressive agmg.

Arthritis affects approximately 80% of people over the age of 55 in the United States.1,12 It is often triggered by injury, a weakened immune system, and/or hereditary factors. Symptoms include inflammation, joint pain, and progressive deterioration of joint surfaces over time which may result in anatomical changes of the joint surface, and edema inside the joint accompanied by tissue debris. This condition demonstrates mechanical instability in the joint related to the wearing away of the cartilage that is responsible for friction-free motion of the joint. The debris causes an inflammatory response that can induce bone overgrowth and osteophyte formation that eventually interferes with joint mobility. Rheumatoid arthritis is a progressive form of arthritis that can be painfully destructive and may cause the interior joint tissues to swell and thicken, resulting in joint disintegration and eventual significant deformity.

Osteophytes or bone spurs are visible indications of a changing mechanical environment and are often found in areas affected by arthritis such as the disc or joint spaces where cartilage has deteriorated. The formation of osteophytes is the body's attempt to halt the motion of the arthritic joint and deal with the degenerative process, but often causes impingement on the surrounding nerve roots.

Ankylosing spondylitis is a chronic hereitable disease characterized by progressive inflammation of the spine with early sacroiliac joint involvement, followed by hardening of the anulus fibrosus and surrounding connective tissue and arthritic changes in the facet joints.5;6 The disease eventually results in a loss of segmental mobility and "stiffening" of the spinal tissues.

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