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The importance of biomechanics for the new millennium
J Orthop Sci (2000) 5:89–91
Editorial The importance of biomechanics for the new millennium Savio Lau-Yuen Woo Director, Musculoskeletal Research Center, Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
Key words: biomechanics, ligaments, knee, injury
“Biomechanics is the middle name of biological structure and function” When Professor Y.C. Fung made this statement in 1998, he indicated that biomechanics research constitutes the investigation of structures at all levels, ranging from molecules, to cell membranes, to tissues, to organs, to the body. At the beginning of the new millennium, it is indeed an exciting time to reflect on the potential of biomechanics. In this editorial, I have chosen to write about my particular area of interest — ligaments. Nevertheless, I do believe the concepts presented are applicable to other areas of orthopedic research. The medial collateral ligament (MCL) of the knee is known to heal spontaneously after injury. However, one problem is that the morphology, biochemistry, and mechanical properties of the healed MCL have failed to return to their uninjured condition, even after long periods of time.4 The cruciate ligaments of the knee have limited healing capability, and surgical reconstruction with tissue grafts is needed. Although outcomes have been reasonably successful for the anterior cruciate ligament (ACL), the same cannot be said for the posterior cruciate ligament (PCL). Significant research efforts are being made to improve the outcome of such knee ligament injuries, and future directions point towards the integration of biological and biomechanical approaches. “Functional tissue engineering” is a concept which offers the potential to improve the quality of ligaments during the healing process. This concept is based on the manipulation of cellular and biochemical mediators to affect protein synthesis. Novel techniques — such as the application of growth factors, gene transfer technology for growth factor delivery, mesen-
chymal stem cell (MSC) therapy, biomatrix scaffolding coupled with seeding of cells, and the mechanical loading of cells — have shown some promise. Among these applications are growth factors such as plateletderived growth factor (PDGF)-BB, epithelial growth factor (EGF), and transforming growth factor (TGF) β1, TGF β2, insulin-like growth factor (IGF), and bone morphogenic proteins (BMPs). Investigators have successfully introduced marker and therapeutic genes into ligaments, using retroviral and adenoviral techniques. Adeno-associated virus is also being explored, as it infects both dividing and nondividing cells, with almost no immune response. Other investigators have taken advantage of non-viral and non-toxic gene transfer techniques, such as hemagglutinating virus of Japan (HVJ)-conjugated liposomes, with which there are few constraints on the size of gene to be delivered. Frank et al.2 hypothesized that decorin, a small leucinerich protein, may play a role in fibrillogenesis. Antisense decorin oligodeoxynucleotides were introduced, using an in-vivo liposome method, to decrease decorin RNA expression and protein synthesis. As a result, large collagen fibrils were formed, and the mechanical properties of the healing ligament were enhanced. Another current area of research uses silicon microgroove surfaces to align fibroblasts in a parallel fashion, aiming to generate a new matrix that resembles the uninjured ligament. It should be noted that the above avenues are all in the early stages of development. By combining appropriate engineering mechanics with other basic science, we believe that the process of ligament healing can be functionally engineered to produce better outcomes. It is hoped that the knowledge gained can be extended to enhance the healing of: (1) the ACL, PCL, and all ligaments, (2) soft tissues in the bone tunnel, and (3) ligament attachment at the insertion sites. From a bioengineering perspective, the robotics/ universal force moment sensor testing system has been
90
S.L.-Y. Woo: Biomechanics, structure and function
a unique development; with it, measurement of the in-situ forces in ligaments can be done with greater accuracy.3 In the coming years, the focus will be to obtain kinematics data in vivo. These data can be used experimentally to determine the in-situ forces of knee ligaments during the same in-vivo activities. Also, the data are needed to validate mathematical models (Fig. 1). These models, in turn, can be used to calculate stresses and strains in ligaments and to
examine the mechanical effects on cellular responses. This combined experimental and mathematical modeling approach offers the opportunity to establish a database on intact ligaments and ligament replacement grafts, based on factors such as sex, age, and size. Hence, database optimization of the variations that occur during ligament reconstruction (ie, graft tension, placement, and position) can be performed on an individual basis. Further, surgical preplanning and postoperative rehabilitation protocols can be customized. Ultimately, the outcome for patients should be improved. Bioengineers and biologists have a reasonably good history of collaboration with orthopedic surgeons. However, in the future, even more integration of disciplines, including biology, biochemistry, biomechanics, and surgery, is necessary. Investigators need to work together in the same laboratory.1 To do this, one must learn to truly respect disciplines other than one’s own, and major efforts are needed to learn the languages of the other fields. I have long believed that it is uncommon for a good biomechanician to also be a good biologist, and vice versa. Finding willing collaborators and developing methods of communication are efficient ways of accomplishing our common goals (see Fig. 2).
Fig. 1. Flow chart detailing the general approach to gain data on the in situ forces, as well as stresses and strains, in the ligaments of the knee and shoulder under loading conditions that involve in-vivo activities. UFS, Universal force moment sensor
References 1. Andriacchi TP, Alexander EJ, Toney MK, et al. A point cluster method for in vivo motion analysis: applied to a study of knee kinematics. J Biomech Eng 1998;120:743–49.
Fig. 2. Collaboration among scientists is an efficient and ideal way to accomplish common goals
S.L.-Y. Woo: Biomechanics, structure and function 2. Frank C, Shrive N, Hiraoka H, et al. Optimization of the biology of soft tissue repair. J Sci Med Sport 1999;2:190–210. 3. Rudy TW, Livesay GA, Woo SL-Y, Fu FH. A combined robotic/ universal force sensor approach to determine in situ forces of knee ligaments. J Biomech 1996;29:1357–60.
91 4. Woo SL-Y, Smith DW, Hildebrand KA, et al. Engineering the healing of the rabbit medial collateral ligament. Med Biol Eng Comput 1998;36:359–64.
Editorial The importance of biomechanics for the new millennium Savio Lau-Yuen Woo Director, Musculoskeletal Research Center, Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
Key words: biomechanics, ligaments, knee, injury
“Biomechanics is the middle name of biological structure and function” When Professor Y.C. Fung made this statement in 1998, he indicated that biomechanics research constitutes the investigation of structures at all levels, ranging from molecules, to cell membranes, to tissues, to organs, to the body. At the beginning of the new millennium, it is indeed an exciting time to reflect on the potential of biomechanics. In this editorial, I have chosen to write about my particular area of interest — ligaments. Nevertheless, I do believe the concepts presented are applicable to other areas of orthopedic research. The medial collateral ligament (MCL) of the knee is known to heal spontaneously after injury. However, one problem is that the morphology, biochemistry, and mechanical properties of the healed MCL have failed to return to their uninjured condition, even after long periods of time.4 The cruciate ligaments of the knee have limited healing capability, and surgical reconstruction with tissue grafts is needed. Although outcomes have been reasonably successful for the anterior cruciate ligament (ACL), the same cannot be said for the posterior cruciate ligament (PCL). Significant research efforts are being made to improve the outcome of such knee ligament injuries, and future directions point towards the integration of biological and biomechanical approaches. “Functional tissue engineering” is a concept which offers the potential to improve the quality of ligaments during the healing process. This concept is based on the manipulation of cellular and biochemical mediators to affect protein synthesis. Novel techniques — such as the application of growth factors, gene transfer technology for growth factor delivery, mesen-
chymal stem cell (MSC) therapy, biomatrix scaffolding coupled with seeding of cells, and the mechanical loading of cells — have shown some promise. Among these applications are growth factors such as plateletderived growth factor (PDGF)-BB, epithelial growth factor (EGF), and transforming growth factor (TGF) β1, TGF β2, insulin-like growth factor (IGF), and bone morphogenic proteins (BMPs). Investigators have successfully introduced marker and therapeutic genes into ligaments, using retroviral and adenoviral techniques. Adeno-associated virus is also being explored, as it infects both dividing and nondividing cells, with almost no immune response. Other investigators have taken advantage of non-viral and non-toxic gene transfer techniques, such as hemagglutinating virus of Japan (HVJ)-conjugated liposomes, with which there are few constraints on the size of gene to be delivered. Frank et al.2 hypothesized that decorin, a small leucinerich protein, may play a role in fibrillogenesis. Antisense decorin oligodeoxynucleotides were introduced, using an in-vivo liposome method, to decrease decorin RNA expression and protein synthesis. As a result, large collagen fibrils were formed, and the mechanical properties of the healing ligament were enhanced. Another current area of research uses silicon microgroove surfaces to align fibroblasts in a parallel fashion, aiming to generate a new matrix that resembles the uninjured ligament. It should be noted that the above avenues are all in the early stages of development. By combining appropriate engineering mechanics with other basic science, we believe that the process of ligament healing can be functionally engineered to produce better outcomes. It is hoped that the knowledge gained can be extended to enhance the healing of: (1) the ACL, PCL, and all ligaments, (2) soft tissues in the bone tunnel, and (3) ligament attachment at the insertion sites. From a bioengineering perspective, the robotics/ universal force moment sensor testing system has been
90
S.L.-Y. Woo: Biomechanics, structure and function
a unique development; with it, measurement of the in-situ forces in ligaments can be done with greater accuracy.3 In the coming years, the focus will be to obtain kinematics data in vivo. These data can be used experimentally to determine the in-situ forces of knee ligaments during the same in-vivo activities. Also, the data are needed to validate mathematical models (Fig. 1). These models, in turn, can be used to calculate stresses and strains in ligaments and to
examine the mechanical effects on cellular responses. This combined experimental and mathematical modeling approach offers the opportunity to establish a database on intact ligaments and ligament replacement grafts, based on factors such as sex, age, and size. Hence, database optimization of the variations that occur during ligament reconstruction (ie, graft tension, placement, and position) can be performed on an individual basis. Further, surgical preplanning and postoperative rehabilitation protocols can be customized. Ultimately, the outcome for patients should be improved. Bioengineers and biologists have a reasonably good history of collaboration with orthopedic surgeons. However, in the future, even more integration of disciplines, including biology, biochemistry, biomechanics, and surgery, is necessary. Investigators need to work together in the same laboratory.1 To do this, one must learn to truly respect disciplines other than one’s own, and major efforts are needed to learn the languages of the other fields. I have long believed that it is uncommon for a good biomechanician to also be a good biologist, and vice versa. Finding willing collaborators and developing methods of communication are efficient ways of accomplishing our common goals (see Fig. 2).
Fig. 1. Flow chart detailing the general approach to gain data on the in situ forces, as well as stresses and strains, in the ligaments of the knee and shoulder under loading conditions that involve in-vivo activities. UFS, Universal force moment sensor
References 1. Andriacchi TP, Alexander EJ, Toney MK, et al. A point cluster method for in vivo motion analysis: applied to a study of knee kinematics. J Biomech Eng 1998;120:743–49.
Fig. 2. Collaboration among scientists is an efficient and ideal way to accomplish common goals
S.L.-Y. Woo: Biomechanics, structure and function 2. Frank C, Shrive N, Hiraoka H, et al. Optimization of the biology of soft tissue repair. J Sci Med Sport 1999;2:190–210. 3. Rudy TW, Livesay GA, Woo SL-Y, Fu FH. A combined robotic/ universal force sensor approach to determine in situ forces of knee ligaments. J Biomech 1996;29:1357–60.
91 4. Woo SL-Y, Smith DW, Hildebrand KA, et al. Engineering the healing of the rabbit medial collateral ligament. Med Biol Eng Comput 1998;36:359–64.