Catálogo de publicaciones - libros

The most promising emergent medical technology of the early twenty-first century is stem-cell therapeutics. Traditionally, stem cells possess two important characteristics: the ability to undergo nearly unlimited self-renewal and the capability to differentiate into many (multipotent/pluripotent) or all (totipotent) mature cell phenotypes. The existence of stem cells and their ability to generate every tissue of the body during embryonic development has been known for many years. Transplant experiments performed in the 1970s, in which single stem cells were injected into early-stage blastulas, produced a chimera of donor and recipient cells in each organ of the resultant animal [, ].

Ontogenetic development is initiated at the time of fertilization and terminates with the differentiation, growth, and maturation of specialized tissues and organs. These developmental processes are characterized by molecular specialization that accompanies cellular differentiation and tissue morphogenesis. Most developmental processes terminate after birth or when animals reach sexual maturity, but some morphogenetic processes are reinitiated in response to injury in specific tissues. One such regenerative process is the repair of skeletal fractures and bone tissue after surgery, a process that recapitulates specific aspects of the initial developmental processes in the course of healing [, ]. Several aspects of the postnatal tissue environment of fracture healing, however, are unique and differ from what occurs in embryological and postnatal development.

Bone allograft transplantation is a common practice; in the United States 650,000 procedures were performed in 1999, a 186% increase from 1990 []. This increase can be attributed to morbidities associated with bone autografts [, , , , ], the increased availability of bone allografts, and the expansion of these applications [, , , , , , , ]. A variety of musculoskeletal allografts are available for different reconstructive applications. Bone allograft is an alternative to autograft because it has osteoconductive properties, acts as a scaffold for bone growth, and induces bone formation by providing osteogenic factors, in addition to mesenchymal precursor cells, osteoblasts, and osteocytes. Although these properties are advantageous, the potential for the transmission of infectious diseases remains a great concern [, , , , , , , , , , , ].

Over the past 30 years, there have been significant advances in the development of biodegradable materials []. In particular, these materials have received attention for use as implants to aid regeneration of orthopedic defects [, ]. Every year more than 3.1 million orthopedic surgeries are performed in the United States alone []. However, although current treatments using nondegradable fixation materials have proven efficacious, tissue-engineering approaches with biodegradable implants are being considered as promising future alternatives [, ]. One possible advantage of these systems is that biodegradable implants can be engineered to provide temporary support for bone fractures, and because they can degrade at a rate matching new tissue formation, their use can eliminate the need for a second surgery [].

The grafting of bone in skeletal reconstruction has become a common task of the orthopedic surgeon. The need for reconstruction or replacement is often the result of trauma, congenital malformations, or cancer. Reconstructive surgery is based upon the principle of replacing defective tissue with viable, functioning alternatives. Various materials have been used to treat the defects, including autogenous bone and alloplastic materials. Grafting materials are necessary to bridge defects or to increase the bone volume. At present, autologous bone is the gold standard, but it has important disadvantages, including donor-site morbidity, limited availability, and unpredictable resorption characteristics. These factors have stimulated the search for other materials that can replace autogenous bone.

Orthopedic injuries resulting from trauma or improper development often require surgical intervention to restore natural tissue function. Currently, over one million operations are performed annually for the surgical reconstruction of bone []. The well-known limitations associated with autografts, allografts, and bone cements have led to the investigation of synthetic polymers as support matrices for bone tissue engineering. Polymers are long-chain molecules that are formed by linking repetitive monomer units. They have been extensively studied for tissue-engineering applications. Constructs designed from these polymers can act as a support matrix to deliver cell populations or induce surrounding tissue ingrowth. The properties of scaffolds directly determine their success in tissue engineering and must be designed specifically for each application.

Every year hundreds of thousands people worldwide receive hip prostheses, implants for bone repair, and surgical repair of degraded cartilage. “Over 15 million people worldwide suffer from knee-joint failure each year due to the breakdown of surrounding cartilage in the joint and the inability of this cartilage to repair itself through the natural regenerative processes of healing in the body” []. Additionally, at least 10 percent of the population suffers from periodontal disease, and one-third of these individuals will require a tooth implant during their lifetime. The standard procedure for repair of orthopedic injuries by tissue grafting is to harvest tissue from the iliac crest or femur of a patient and surgically placing it at the injury site [].

Bone is a living material composed of cells and an extracellular matrix (ECM) that has a multi-component structure []. The ECM of bone is composed of three phases: an inorganic mineral phase, an organic phase, and an aqueous phase. The inorganic phase of bone is calcium hydroxyapatite, Ca(PO)(OH). The organic phase consists primarily of collagen fibers and associated noncollagenous ECM proteins. The molecular configuration of collagen provides binding sites for hydroxyapatite crystal nucleation and growth. The ECM is created and maintained by active bone cells: osteoblasts, osteoclasts, and osteocytes. Osteoblasts and osteocytes are involved in bone formation and maintenance, respectively, whereas osteoclasts promote resorption of bone [], []. Bone is, in general, dynamic and constantly being remodeled by the action of these cells, and thus can regenerate itself.

The teeth are implanted in depressions within alveolar bone and are surrounded by the periodontium which consists of bone, a suspensory ligament (the periodontal ligament), cementum on the root surface, and gingiva. In health, the bone tissue is located approximately 2 mm below the cementoenamel junction which separates the crown of the tooth and its root from the bone (Fig. 9.1). From a functional viewpoint, the periodontium is a unique, very dynamic and adaptable tissue. The periodontal ligament has one of the fastest turnover rates of connective tissue in the body and maintains its dimensions even if the teeth are moved or the ligament is regenerated. At the same time, the periodontium provides support for the tooth, resists biting forces, and, importantly, provides a seal around the tooth. It is important to recognize that the tooth is a solid structure that extends from inside the body to outside the body.

Computational models provide a platform that is equivalent to an in vivo, in vitro, and in situ or ex vivo model platform. Indeed, the National Institutes of Health have made the development of predictive computational models a high priority of the “Roadmap for the Future” (http://nihroadmap.nih.gov/overview.asp; see especially “New Pathways to Discovery”). The power of computational models lies in their usefulness to predict which variables are most likely to influence a given result, simulation of the system response to changes in that variable, and optimization of system variables to achieve a desired bio logical effect. Typically, these models are computer representations of the actual system, based on experimentally determined parameters and system variables; increasingly these computer models are referred to as in silico models (Fig. 10.1).