- Email: [email protected]
Tissue-engineered ligaments
BIOMATERIALS FOCUS
RESEARCH NEWS
With the growth in the aged population and the need to extend average individual healthspan, biomaterials have an increasingly important role in the development of new generation medical devices, drug delivery systems, and medical diagnostic technologies. This column seeks to provide an insight into the latest developments in biomedical materials and related technologies through brief synopses and expert commentaries of recent presentations, publications, and patents. Andrew Lloyd, University of Brighton.
Tissue-engineered ligaments There is considerable interest in the development of tissue engineered approaches to address the increasing incidence of anterior cruciate ligament failures. Existing surgical procedures are reliant on the use of autographs, which often result in donor site pain and tendonitis, long recovery periods, and muscle atrophy. In the development of novel tissue-engineered anterior cruciate ligaments, structure-function optimization is essential if graft failure is to be avoided. A key challenge is the need to match the complex mechanical properties of the native human anterior cruciate ligament, which consists of individual fiber bundles arranged in a helical geometry. This arrangement distributes the load equally throughout the ligament during flexionextension, thereby stabilizing
the knee. In an attempt to mimic these properties, Gregory H. Altman at Tufts University and coworkers at University Hospital Basel and the New England Medical Center have used a novel silkfiber based matrix in combination with a wire rope design to match the anterior cruciate ligament in linear stiffness and ultimate tensile strength [Biomaterials (2002) 23, 4131-4141]. Silk has a number of particular advantages over other similar materials including the mechanical strength of the protein, biocompatibility of the processed material, and slow rate of in vivo degradation. Fatigue analysis of the material in saline indicates an expected matrix lifetime of about one year in vivo before failure. This is likely to provide adequate time for tissue remodeling and
Scanning electron micrograph showing adherence, proliferation, and cell sheet formation by human bone marrow stromal cells on the silk cord matrix (a)prior to seeding; (b) following seeding; (c) after one day; and (d) 14 days later. Scale bar is 100 µm. (Reproduced with permission from Elsevier Science Ltd.)
strengthening in vivo. The group have also demonstrated that the silkmatrix supports the attachment, growth, and differentiation of adult human progenitor bone marrow stromal cells using electron microscopy, DNA quantification, and the
expression of markers for biological remodeling. The optimization of the mechanical properties through the use of wire-rope geometry and the inherent biocompatibility of this silk-based material offers an important new scaffold for the development of replacement artificial ligaments.
applications because they could be readily administered by injection. To investigate the biocompatibility of these materials for biomedical application, Giuseppe Molinaro at the Université de Montréal and coworkers from the Université de Liége have investigated the inflammatory effects of a range of these gels on injection into the hindpaw of rats [Biomaterials (2002) 23, 2717-2722]. The study demonstrates that all four
systems tested trigger a nonspecific inflammatory response, with the systems prepared from more highly deacetylated chitosans producing less response. It appears that the inflammatory response may be linked to the degradation of the polymers as the more highly deacetylated polymer systems degrade more slowly, generating fewer fragments and a less pronounced inflammatory response.
An inflammatory response In recent years there has been increasing interest in the use of biomaterials derived from the biopolymer chitosan, which is obtained on alkaline deacetylation of chitin from the exoskeleton of shell fish – an industrial by-product. Previous studies of the biocompatibility of chitosanbased biomaterials have had different outcomes and suggest that the biological properties of the material may be highly dependent on the
degree of deacetylation. Recent studies have shown that solutions of chitosan and glycerol-2-phosphate undergo a temperature-controlled, pH-dependent solution--gel transition around normal body temperatures [Chenite, A., et al., Biomaterials (2000) 21, 2155-2161]. As such systems remain liquid at room temperature, but gel on heating to body temperature, these thermosetting gels may have useful drug delivery
September 2002
9
RESEARCH NEWS
With the growth in the aged population and the need to extend average individual healthspan, biomaterials have an increasingly important role in the development of new generation medical devices, drug delivery systems, and medical diagnostic technologies. This column seeks to provide an insight into the latest developments in biomedical materials and related technologies through brief synopses and expert commentaries of recent presentations, publications, and patents. Andrew Lloyd, University of Brighton.
Tissue-engineered ligaments There is considerable interest in the development of tissue engineered approaches to address the increasing incidence of anterior cruciate ligament failures. Existing surgical procedures are reliant on the use of autographs, which often result in donor site pain and tendonitis, long recovery periods, and muscle atrophy. In the development of novel tissue-engineered anterior cruciate ligaments, structure-function optimization is essential if graft failure is to be avoided. A key challenge is the need to match the complex mechanical properties of the native human anterior cruciate ligament, which consists of individual fiber bundles arranged in a helical geometry. This arrangement distributes the load equally throughout the ligament during flexionextension, thereby stabilizing
the knee. In an attempt to mimic these properties, Gregory H. Altman at Tufts University and coworkers at University Hospital Basel and the New England Medical Center have used a novel silkfiber based matrix in combination with a wire rope design to match the anterior cruciate ligament in linear stiffness and ultimate tensile strength [Biomaterials (2002) 23, 4131-4141]. Silk has a number of particular advantages over other similar materials including the mechanical strength of the protein, biocompatibility of the processed material, and slow rate of in vivo degradation. Fatigue analysis of the material in saline indicates an expected matrix lifetime of about one year in vivo before failure. This is likely to provide adequate time for tissue remodeling and
Scanning electron micrograph showing adherence, proliferation, and cell sheet formation by human bone marrow stromal cells on the silk cord matrix (a)prior to seeding; (b) following seeding; (c) after one day; and (d) 14 days later. Scale bar is 100 µm. (Reproduced with permission from Elsevier Science Ltd.)
strengthening in vivo. The group have also demonstrated that the silkmatrix supports the attachment, growth, and differentiation of adult human progenitor bone marrow stromal cells using electron microscopy, DNA quantification, and the
expression of markers for biological remodeling. The optimization of the mechanical properties through the use of wire-rope geometry and the inherent biocompatibility of this silk-based material offers an important new scaffold for the development of replacement artificial ligaments.
applications because they could be readily administered by injection. To investigate the biocompatibility of these materials for biomedical application, Giuseppe Molinaro at the Université de Montréal and coworkers from the Université de Liége have investigated the inflammatory effects of a range of these gels on injection into the hindpaw of rats [Biomaterials (2002) 23, 2717-2722]. The study demonstrates that all four
systems tested trigger a nonspecific inflammatory response, with the systems prepared from more highly deacetylated chitosans producing less response. It appears that the inflammatory response may be linked to the degradation of the polymers as the more highly deacetylated polymer systems degrade more slowly, generating fewer fragments and a less pronounced inflammatory response.
An inflammatory response In recent years there has been increasing interest in the use of biomaterials derived from the biopolymer chitosan, which is obtained on alkaline deacetylation of chitin from the exoskeleton of shell fish – an industrial by-product. Previous studies of the biocompatibility of chitosanbased biomaterials have had different outcomes and suggest that the biological properties of the material may be highly dependent on the
degree of deacetylation. Recent studies have shown that solutions of chitosan and glycerol-2-phosphate undergo a temperature-controlled, pH-dependent solution--gel transition around normal body temperatures [Chenite, A., et al., Biomaterials (2000) 21, 2155-2161]. As such systems remain liquid at room temperature, but gel on heating to body temperature, these thermosetting gels may have useful drug delivery
September 2002
9