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Osteoarthritis, Exercise, and Tissue Engineering: A Stimulating Triad for Health Professionals

Osteoarthritis, Exercise, and Tissue Engineering: A Stimulating Triad for Health Professionals Hindawi Journal of Aging Research Volume 2019, Article ID 1935806, 6 pages https://doi.org/10.1155/2019/1935806 Review Article Osteoarthritis, Exercise, and Tissue Engineering: A Stimulating Triad for Health Professionals 1,2 3 2,4 Pedro Morouço , Cristiana Fernandes, and Rita Santos-Rocha Polytechnic Institute of Leiria, School of Education and Social Sciences (ESECS), Leiria, Portugal Universidade de Lisboa, Faculdade de Motricidade Humana, Laboratory of Biomechanics and Functional Morphology, Interdisciplinary Centre for the Study of Human Performance (CIPER), Cruz Quebrada, Portugal Polytechnic Institute of Leiria, Centre for Rapid and Sustainable Product Development (CDRsp), Marinha Grande, Portugal Polytechnic Institute of Santarem, Sport Sciences School of Rio Maior (ESDRM), Rio Maior, Portugal Correspondence should be addressed to Pedro Morouço; pedro.morouco@ipleiria.pt Received 5 December 2018; Revised 13 March 2019; Accepted 27 March 2019; Published 2 May 2019 Academic Editor: Jean-Francois Grosset Copyright © 2019 Pedro Morouço et al. -is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Osteoarthritis (OA) is a degenerative disease, promoted by abnormal chronic mechanical loading over the joint, for instance, due to excessive body mass. Patients frequently report pain, fatigue, and limitations in specific functional daily activities. Regarding the treatment of OA, two nonpharmacological options are available. However, it is not clear which type and intensity of exercise have better outcomes in treatment and how tissue engineering can be a promising field due to the mechanical load implants will suffer. -e aims of this work were to investigate (1) the main characteristics, prevalence, and consequences of OA; (2) the exercise prescription guidelines and whether exercise interventions have a positive effect on OA treatment; and (3) the novel im- provements on tissue engineering for OA treatment. Both patients and practitioners should be aware that benefits may come from prescribed and supervised exercise. Recent studies have highlighted that an optimal balance between exercise and nutritional income should be widely recommended. Regarding tissue engineering, significant steps towards the development of implants that mimic the native tissue have been taken. -us, further studies should focus on the impact that exercise (repetitive loading) might have on cartilage regeneration. Finally, suggestions for future research were proposed. responding to abnormal (e.g., resistance training) me- 1. Introduction chanical loading over time. It may be questioned if a patient Osteoarthritis (OA) is a degenerative disease, promoted by treated with one of the mentioned matrices abnormal chronic mechanical loading over the joint, for (e.g., MaioRegen ) should be enrolled in exercise to de- instance, due to excessive body mass [1]. Patients frequently crease his/her body mass; if yes, with which type of exercise. report pain, fatigue, and limitations in specific functional Several issues demonstrate the stimulating triad that re- activities. -us, exercise should be a clear recommendation searchers should look up to for promising treatments of for OA prevention, but it is not clear which type and in- osteochondral defects. tensity [2]. It will increase the load over the joints, and if We do believe that the scientific communities around there is joint malalignment, it will be worse than better [3]. rheumatic disorders should work together and, more im- On the other hand, recent improvements in tissue engi- portantly, know what other disciplines are advancing. neering have demonstrated the suitability of novel bilayer Physical exercise specialists will soon have clients treated scaffolds [4]. However, it is unclear how these scaffolds will with bioengineered implants, and bioengineers should pay behave responding to the normal mechanical loading over attention to the repetitive load that a scaffold must stand for, time. Moreover, it is demonstrated that mechanical loading even after implanted. Our aim is to foster the potential is an adequate stimulus for cartilage regeneration [5, 6]. multidiscipline approach regarding this health issue -erefore, it is unclear how these scaffolds will behave (Figure 1). 2 Journal of Aging Research Osteoarthritis Prevention Tissue engineering Cells + scaffolds + growth factors Body weight reduction Mechanical loading � Type Bioreactor � Hypoxia � Mechanical loading � Volume � Intensity Treatment Physical exercise Figure 1: Illustrative diagram of the relationships between osteoarthritis, physical exercise, and tissue engineering. -e focus of this manuscript was on the close re- Table 1: Top facts related to OA. lationship between OA, exercise, and tissue engineering. -e (i) Disability due to musculoskeletal disorders increased by 45% aims were to investigate (1) the main characteristics, prev- from 1990 to 2010 [31] alence, and consequences of OA; (2) the exercise pre- (ii) OA is the fastest increasing health condition, affecting over 250 million people worldwide [32] scription guidelines, and whether exercise interventions (iii) It is not exclusive for the elderly: more than 50% of adults with have a positive effect on OA treatment; and (3) the novel knee OA are under 65 [30] improvements on tissue engineering in the treatment of OA. (iv) Two out of three people with obesity are at risk for developing knee OA in their lifetime [33] 2. Main Characteristics, Prevalence, and (v) Knee OA is the 11th leading cause of disability and shows a growing trend [34] Consequences of Osteoarthritis (vi) People with OA have a 16% increased risk of developing Cartilage is a tissue with enormous complexity that is found cardiovascular disease compared to those without [35] in the human body in three types: hyaline cartilage, fibro- cartilage, and elastic cartilage. -e articular cartilage is a flexible connective tissue that aligns the surface of the bones such as found in certain occupations [18]. Either way, the in the synovial joints throughout the body, allowing a distinct categories do not alter the clinical practice and therapeutic choice. Nevertheless, there are known risk movement with almost zero friction on its surface. -e extracellular matrix is stratified into four distinct (archi- factors, such as overweight or obesity, history of joint injury tecturally and biochemically) zones (the surface zone, the or surgery, genetic predisposition, and aging [19]. OA is midzone, the deep zone, and the calcified zone), which characterized by joint pain and stiffness, usually associated together give rise to its viscoelastic properties [4, 7]. It is with degeneration of the joint cartilage, commonly in hands, avascular, alymphatic, and aneural and, therefore, has a very hips, spine, and knees [20]. It is estimated that 18% of low endogenous regeneration capacity [8]. Either way, its women and 9.6% of men over 60 years suffer from symp- structure and mechanical properties allow it to handle with tomatic OA [21]. Moreover, 25% to 50% with OA will have repetitive load forces over decades. -us, damage caused to symptoms [20]. In addition, 80% of people with OA will the joints by trauma or disease usually requires exogenous have movement limitations and 25% will not be able to intervention to stimulate regeneration [9, 10]. perform daily life activities. -is pathology is associated with factors such as aging, obesity, nutritional deficiencies, and According to the World Health Organization, cartilage- related diseases are one of the major societal challenges physical (in)activity; so that, more than 250 million people (Table 1). -e prevention of joint cartilage degeneration is an are affected with chronic OA. important health issue with a significant number of repair Aging has been connected to chronic low-grade in- strategies to treat an articular cartilage injury, some already flammation, which is sometimes termed inflammation [22]. available and others in an on-going research status [11–17]. -ese changes resulting from age compromise the effec- OA is a heterogeneous group of joint disorders, which may tiveness of cartilage repair, which contributes to an increased be categorized as primary (idiopathic) or secondary. While incidence of OA [19, 23]. As a person ages, there is an primary OA can be defined as a process occurring with an increase in fat mass. It happens because there is an increase in the number of proinflammatory adipocytes and macro- absence of an obvious underlying abnormality, secondary OA is often the result of injury (trauma) or repetitive motion phages in the adipose tissue that produce cytosines and Journal of Aging Research 3 adipokines [24, 25], as well as fibroblast and vascular en- clarifying the most adequate prescription according to the dothelial growth factors [26]. It is thus admitted that an stage of OA, is crucial [41, 43]. -e tolerance volume may vary from one day to the next, increase in the age-related fat volume will contribute to OA. For instance, a study on fat-conditioned medium demon- which will imply flexibility in activities and exercise options. strated that removing the infrapatellar fat pads from the Either way, the human body is as a well-established sensorial terminal knee made it become protective [27]. Accordingly, network to guide us. When the joints are sore and inflamed, it is critical to come up with more research to underline the intensity should be reduced to keep the load within its mechanisms related to the delay in the loss of function in tolerance. As rule of thumb, a meta-regression analysis more than one system [19]. In the 90s, Volpin et al. [28] and stated that focus should be on improving aerobic capacity, Honkonen [29] studied the influence of age on the risk of quadriceps muscle strength, or lower extremity perfor- developing posttraumatic OA and showed that OA increases mance, and the program should be supervised and carried out 3 times a week [44]. As well as, to maintain healthy 3 to 4 times after age 50 [23]. However, more recently, due to the cotemporaneous lifestyle, the incidence of OA in early joints, a proper balance of the amount and type of exercise is necessary. -e development of structured exercises should ages has been increasing [30]. -is incidence clearly justifies the need to carry out research that contributes to the provide enough options to allow the patient to flex the weakening of the problem through the interventionist, in- activity options and to maintain the load within the joint tegrated and multidisciplinary approaches. with different training parameters. -is can differentiate From our perspective, regarding the aim of achieving between the amount of weight used, the volume of repeti- significant inputs to overcome, or at least minimize this tion, and among others [9]. Most important, the patient societal problem, two interdependent main topics should be should like and be motivated for the proposed activities. addressed: prevention and treatment. Otherwise, his/her engagement will be insufficient to obtain the intended results. Exercise prescription should take into consideration the individual’s disease activity, pain, func- 3. Exercise for the Prevention of Osteoarthritis tional limitations, and personal preferences to optimize adoption and adherence to exercise [20]. Special consider- Although mechanical stimulation plays a vital role in maintaining cartilage homeostasis, excessive loading is a ations should include avoiding strenuous exercises during acute flare-ups; advising that small amount of discomfort in known contributor to the development of degenerative joint diseases, such as OA. It is characterized by damaging the the muscles or joints during or immediately after exercise is articular cartilage with the development of osteophytes and common following performance of unfamiliar exercise; inflammation of the synovial membrane [36]. Accordingly, substituting the program with alternative exercises when excessive mechanical compression may induce degradation specific exercises exacerbate joint pain; and wearing ap- of the matrix. -at is why OA is strongly associated with propriate shoes that provide good shock absorption and mechanical risk factors, such as obesity, joint overload, or stability are equally important [20, 45]. Likewise, both patients and practitioners should be injury, making it relevant data for prevention [37]. -ere- fore, the development of adequate exercise programs for an aware that benefits may come from prescribed and super- vised exercise, but also from a more active daily lifestyle elderly population (a high-risk population) and its massive dissemination is mandatory [38]. Different types of exercises [46–48]. (e.g., resistance training and water-based workout) may induce significant effects in the prevention of this pathology 4. Tissue Engineering for the [39, 40]. Treatment of Osteoarthritis It should be highlighted that studies have shown that most exercise does not aggravate the symptoms nor in- Tissue engineering (TE) emerged in the 1980s with a colossal crease the progression of arthritis [20]. Indeed, health potential due to the complexity of human tissues. -e main professionals should embrace the idea that exercise is not goal of TE is to develop biological substitutes that restore, only safe but also generally reported to reduce pain, fatigue, maintain, or enhance the function of tissues and organs inflammation, and disease activity. For instance, both high- based on materials engineering and life sciences [49]. Its (i.e., running) and low- (i.e., walking) intensity aerobic main challenge is to provide an adequate function according exercises appear to be effective in improving functional to the tailored structure. In fact, choosing the right approach status, gait, pain, and aerobic capacity [41]. Moreover, to tissue regeneration is a huge concern for all researchers in resistance training and flexibility exercises are also im- this field. portant, as well as incorporating functional exercises to -e replacement of tissues (such as bone or cartilage) or improve neuromuscular control, balance, and ability to joints with allograft materials includes the risk of infections perform activities of daily living [20]. Although it is well by viruses (such as HIV and hepatitis C), graft vs. host accepted that exercise maintains and improves strength disease [50] or even, chondrocytes can die during the process and aerobic capacity [41], the results available in the lit- [51]. Also, the use of grafts can only be applied to damaged erature are inconclusive. Minimizing or preventing func- areas of less than 2 cm [15]. Accordingly, researchers have tional decline attenuates pain and joint stiffness and aids in been interested in developing alternative approaches for weight control [20, 38, 42]. Still, the development of new restoring joint functionality, which can be translated to investigations (through randomized controlled trials), clinical practice. Although there has been an enormous 4 Journal of Aging Research situ approach with a biopen to repair a full-thickness amount of work with the goal of regenerating cartilage, a personalized construction has not yet been achieved and chondral defect [62] or a 4D bioprinting technology that fabricates dynamic structures improves the cartilage and disseminated. Cartilage has a major role in providing joints with a surface that combines low friction with high lubri- bone regeneration [63, 64]. Undoubtedly, significant efforts cation [52]; thus, a deeper knowledge on cartilage charac- are being developed worldwide in the fields of tissue en- terization, bridging the gap between anatomy and gineering and regenerative medicine, but full osteochondral physiology, may lead the way for better implants aiming restoration remains a paramount challenge; it should not be cartilage repair and regeneration [53]. forgotten that OA is much more than a failure in the car- -e regeneration of articular cartilage resulting from tilage. Total contemplation over osteochondral defects should be considered: anatomy, structure and composition degenerative joint disease, such as OA, is an emerging area under investigation using TE approaches. Recent in- resembling native tissue; biomechanics, ability to yield similar mechanical behavior; and physiology, fully restore vestigations highlighted promising regenerative strategies [37, 54]. For instance, the implantation of an autologous joint functionality [65]. -e different compositions and mechanical properties of bone and cartilage indicate the chondrocytes matrix and the immunization of autologous chondrocytes promise high potential for the regeneration of complexity of this tissue interface, making it challenging for hyaline cartilage [37]. Some strategies are already available the design and fabrication of tissue engineered scaffolds (for on the market and others under investigation: palliative; more details, we have recently published a review on bio- microfracture grafts; cell-based; whole tissue trans- fabrication for osteochondral tissue [4]). plantation; scaffold-based or cell plus scaffold-based; and hydrogels-based or cell plus hydrogel-based. Accordingly, 5. Conclusion we might question that why is OA a burden health problem? OA remains in constant discussion and evolution, as it Probably, because there is a lack of customization on the continues to be a challenging, frustrating, and costly used approaches; because experiments should look for problem. It is not only vital to understand the science behind higher reliability; and because randomized controlled trials the structure and function of articular cartilage components are needed to bridge the gap between the labs and the but also how they interact with risk factors. In this way, clinicians. health professionals should act preventively, with adequate For instance, not long ago, it was reported that most choices of lifestyles for the long-term health of their patient’s commonly used three-dimensional (3D) scaffold architec- joints, as well as contributing to the optimization and tures in cartilage TE were porous 3D sponges [55]. -is customization of treatment by TE. nonconventional procedure does not allow control over the inner architecture, thus, not guaranteeing the desired interconnectivity between pores. Embracing technology Disclosure advancements, TE overcomes some of the mentioned -e content is solely the responsibility of the authors and drawbacks, in particular providing a customized design [56]. does not necessarily represent the views/opinions of any Additive manufacturing (AM), also known as 3D printing, organization. -e present manuscript has not been pub- technologies allow the production of complex 3D structures lished elsewhere or is not being considered for publication with a high level of control, predefined geometry, size, and elsewhere, and the research reported will not be submitted interconnected pores, in a reproducible way [57]. -is for publication elsewhere until a final decision has been controlled organization enhances the vascularization and, made as to its acceptability by the Journal of Aging Research. thus, transport of oxygen and nutrients throughout the whole structure, providing an adequate biomechanical en- vironment for tissue regeneration [58]. -e recent ad- Conflicts of Interest vancements in AM have permitted the design and -e authors declare that they have no conflicts of interest. fabrication of patient-specific scaffolds that possess struc- tural and functional features comparable to the native tissue. Acknowledgments It allows for design and fabrication using tissue images captured with commonly used medical imaging techniques -is research was supported by the European Regional De- such as computer tomography (CT) and magnetic resonance velopment Fund (FEDER), through COMPETE2020 under imaging (MRI) that are readily available in hospitals, the PT2020 program (POCI-01-0145-FEDER-023423), and something that conventional fabrication techniques lack. by the Portuguese Foundation for Science and Technology Recently, hydrogel scaffolds have been developed [59]. (UID/Multi/04044/2019). -ese hydrogels are designed to provide cells with a fully hydrated 3D environment, comparable to the native tissue References extracellular matrix. However, hydrogels have inadequate mechanical properties that are unfavorable for embedded [1] T. M. Griffin and F. 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Osteoarthritis, Exercise, and Tissue Engineering: A Stimulating Triad for Health Professionals

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Copyright © 2019 Pedro Morouço et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Hindawi Journal of Aging Research Volume 2019, Article ID 1935806, 6 pages https://doi.org/10.1155/2019/1935806 Review Article Osteoarthritis, Exercise, and Tissue Engineering: A Stimulating Triad for Health Professionals 1,2 3 2,4 Pedro Morouço , Cristiana Fernandes, and Rita Santos-Rocha Polytechnic Institute of Leiria, School of Education and Social Sciences (ESECS), Leiria, Portugal Universidade de Lisboa, Faculdade de Motricidade Humana, Laboratory of Biomechanics and Functional Morphology, Interdisciplinary Centre for the Study of Human Performance (CIPER), Cruz Quebrada, Portugal Polytechnic Institute of Leiria, Centre for Rapid and Sustainable Product Development (CDRsp), Marinha Grande, Portugal Polytechnic Institute of Santarem, Sport Sciences School of Rio Maior (ESDRM), Rio Maior, Portugal Correspondence should be addressed to Pedro Morouço; pedro.morouco@ipleiria.pt Received 5 December 2018; Revised 13 March 2019; Accepted 27 March 2019; Published 2 May 2019 Academic Editor: Jean-Francois Grosset Copyright © 2019 Pedro Morouço et al. -is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Osteoarthritis (OA) is a degenerative disease, promoted by abnormal chronic mechanical loading over the joint, for instance, due to excessive body mass. Patients frequently report pain, fatigue, and limitations in specific functional daily activities. Regarding the treatment of OA, two nonpharmacological options are available. However, it is not clear which type and intensity of exercise have better outcomes in treatment and how tissue engineering can be a promising field due to the mechanical load implants will suffer. -e aims of this work were to investigate (1) the main characteristics, prevalence, and consequences of OA; (2) the exercise prescription guidelines and whether exercise interventions have a positive effect on OA treatment; and (3) the novel im- provements on tissue engineering for OA treatment. Both patients and practitioners should be aware that benefits may come from prescribed and supervised exercise. Recent studies have highlighted that an optimal balance between exercise and nutritional income should be widely recommended. Regarding tissue engineering, significant steps towards the development of implants that mimic the native tissue have been taken. -us, further studies should focus on the impact that exercise (repetitive loading) might have on cartilage regeneration. Finally, suggestions for future research were proposed. responding to abnormal (e.g., resistance training) me- 1. Introduction chanical loading over time. It may be questioned if a patient Osteoarthritis (OA) is a degenerative disease, promoted by treated with one of the mentioned matrices abnormal chronic mechanical loading over the joint, for (e.g., MaioRegen ) should be enrolled in exercise to de- instance, due to excessive body mass [1]. Patients frequently crease his/her body mass; if yes, with which type of exercise. report pain, fatigue, and limitations in specific functional Several issues demonstrate the stimulating triad that re- activities. -us, exercise should be a clear recommendation searchers should look up to for promising treatments of for OA prevention, but it is not clear which type and in- osteochondral defects. tensity [2]. It will increase the load over the joints, and if We do believe that the scientific communities around there is joint malalignment, it will be worse than better [3]. rheumatic disorders should work together and, more im- On the other hand, recent improvements in tissue engi- portantly, know what other disciplines are advancing. neering have demonstrated the suitability of novel bilayer Physical exercise specialists will soon have clients treated scaffolds [4]. However, it is unclear how these scaffolds will with bioengineered implants, and bioengineers should pay behave responding to the normal mechanical loading over attention to the repetitive load that a scaffold must stand for, time. Moreover, it is demonstrated that mechanical loading even after implanted. Our aim is to foster the potential is an adequate stimulus for cartilage regeneration [5, 6]. multidiscipline approach regarding this health issue -erefore, it is unclear how these scaffolds will behave (Figure 1). 2 Journal of Aging Research Osteoarthritis Prevention Tissue engineering Cells + scaffolds + growth factors Body weight reduction Mechanical loading � Type Bioreactor � Hypoxia � Mechanical loading � Volume � Intensity Treatment Physical exercise Figure 1: Illustrative diagram of the relationships between osteoarthritis, physical exercise, and tissue engineering. -e focus of this manuscript was on the close re- Table 1: Top facts related to OA. lationship between OA, exercise, and tissue engineering. -e (i) Disability due to musculoskeletal disorders increased by 45% aims were to investigate (1) the main characteristics, prev- from 1990 to 2010 [31] alence, and consequences of OA; (2) the exercise pre- (ii) OA is the fastest increasing health condition, affecting over 250 million people worldwide [32] scription guidelines, and whether exercise interventions (iii) It is not exclusive for the elderly: more than 50% of adults with have a positive effect on OA treatment; and (3) the novel knee OA are under 65 [30] improvements on tissue engineering in the treatment of OA. (iv) Two out of three people with obesity are at risk for developing knee OA in their lifetime [33] 2. Main Characteristics, Prevalence, and (v) Knee OA is the 11th leading cause of disability and shows a growing trend [34] Consequences of Osteoarthritis (vi) People with OA have a 16% increased risk of developing Cartilage is a tissue with enormous complexity that is found cardiovascular disease compared to those without [35] in the human body in three types: hyaline cartilage, fibro- cartilage, and elastic cartilage. -e articular cartilage is a flexible connective tissue that aligns the surface of the bones such as found in certain occupations [18]. Either way, the in the synovial joints throughout the body, allowing a distinct categories do not alter the clinical practice and therapeutic choice. Nevertheless, there are known risk movement with almost zero friction on its surface. -e extracellular matrix is stratified into four distinct (archi- factors, such as overweight or obesity, history of joint injury tecturally and biochemically) zones (the surface zone, the or surgery, genetic predisposition, and aging [19]. OA is midzone, the deep zone, and the calcified zone), which characterized by joint pain and stiffness, usually associated together give rise to its viscoelastic properties [4, 7]. It is with degeneration of the joint cartilage, commonly in hands, avascular, alymphatic, and aneural and, therefore, has a very hips, spine, and knees [20]. It is estimated that 18% of low endogenous regeneration capacity [8]. Either way, its women and 9.6% of men over 60 years suffer from symp- structure and mechanical properties allow it to handle with tomatic OA [21]. Moreover, 25% to 50% with OA will have repetitive load forces over decades. -us, damage caused to symptoms [20]. In addition, 80% of people with OA will the joints by trauma or disease usually requires exogenous have movement limitations and 25% will not be able to intervention to stimulate regeneration [9, 10]. perform daily life activities. -is pathology is associated with factors such as aging, obesity, nutritional deficiencies, and According to the World Health Organization, cartilage- related diseases are one of the major societal challenges physical (in)activity; so that, more than 250 million people (Table 1). -e prevention of joint cartilage degeneration is an are affected with chronic OA. important health issue with a significant number of repair Aging has been connected to chronic low-grade in- strategies to treat an articular cartilage injury, some already flammation, which is sometimes termed inflammation [22]. available and others in an on-going research status [11–17]. -ese changes resulting from age compromise the effec- OA is a heterogeneous group of joint disorders, which may tiveness of cartilage repair, which contributes to an increased be categorized as primary (idiopathic) or secondary. While incidence of OA [19, 23]. As a person ages, there is an primary OA can be defined as a process occurring with an increase in fat mass. It happens because there is an increase in the number of proinflammatory adipocytes and macro- absence of an obvious underlying abnormality, secondary OA is often the result of injury (trauma) or repetitive motion phages in the adipose tissue that produce cytosines and Journal of Aging Research 3 adipokines [24, 25], as well as fibroblast and vascular en- clarifying the most adequate prescription according to the dothelial growth factors [26]. It is thus admitted that an stage of OA, is crucial [41, 43]. -e tolerance volume may vary from one day to the next, increase in the age-related fat volume will contribute to OA. For instance, a study on fat-conditioned medium demon- which will imply flexibility in activities and exercise options. strated that removing the infrapatellar fat pads from the Either way, the human body is as a well-established sensorial terminal knee made it become protective [27]. Accordingly, network to guide us. When the joints are sore and inflamed, it is critical to come up with more research to underline the intensity should be reduced to keep the load within its mechanisms related to the delay in the loss of function in tolerance. As rule of thumb, a meta-regression analysis more than one system [19]. In the 90s, Volpin et al. [28] and stated that focus should be on improving aerobic capacity, Honkonen [29] studied the influence of age on the risk of quadriceps muscle strength, or lower extremity perfor- developing posttraumatic OA and showed that OA increases mance, and the program should be supervised and carried out 3 times a week [44]. As well as, to maintain healthy 3 to 4 times after age 50 [23]. However, more recently, due to the cotemporaneous lifestyle, the incidence of OA in early joints, a proper balance of the amount and type of exercise is necessary. -e development of structured exercises should ages has been increasing [30]. -is incidence clearly justifies the need to carry out research that contributes to the provide enough options to allow the patient to flex the weakening of the problem through the interventionist, in- activity options and to maintain the load within the joint tegrated and multidisciplinary approaches. with different training parameters. -is can differentiate From our perspective, regarding the aim of achieving between the amount of weight used, the volume of repeti- significant inputs to overcome, or at least minimize this tion, and among others [9]. Most important, the patient societal problem, two interdependent main topics should be should like and be motivated for the proposed activities. addressed: prevention and treatment. Otherwise, his/her engagement will be insufficient to obtain the intended results. Exercise prescription should take into consideration the individual’s disease activity, pain, func- 3. Exercise for the Prevention of Osteoarthritis tional limitations, and personal preferences to optimize adoption and adherence to exercise [20]. Special consider- Although mechanical stimulation plays a vital role in maintaining cartilage homeostasis, excessive loading is a ations should include avoiding strenuous exercises during acute flare-ups; advising that small amount of discomfort in known contributor to the development of degenerative joint diseases, such as OA. It is characterized by damaging the the muscles or joints during or immediately after exercise is articular cartilage with the development of osteophytes and common following performance of unfamiliar exercise; inflammation of the synovial membrane [36]. Accordingly, substituting the program with alternative exercises when excessive mechanical compression may induce degradation specific exercises exacerbate joint pain; and wearing ap- of the matrix. -at is why OA is strongly associated with propriate shoes that provide good shock absorption and mechanical risk factors, such as obesity, joint overload, or stability are equally important [20, 45]. Likewise, both patients and practitioners should be injury, making it relevant data for prevention [37]. -ere- fore, the development of adequate exercise programs for an aware that benefits may come from prescribed and super- vised exercise, but also from a more active daily lifestyle elderly population (a high-risk population) and its massive dissemination is mandatory [38]. Different types of exercises [46–48]. (e.g., resistance training and water-based workout) may induce significant effects in the prevention of this pathology 4. Tissue Engineering for the [39, 40]. Treatment of Osteoarthritis It should be highlighted that studies have shown that most exercise does not aggravate the symptoms nor in- Tissue engineering (TE) emerged in the 1980s with a colossal crease the progression of arthritis [20]. Indeed, health potential due to the complexity of human tissues. -e main professionals should embrace the idea that exercise is not goal of TE is to develop biological substitutes that restore, only safe but also generally reported to reduce pain, fatigue, maintain, or enhance the function of tissues and organs inflammation, and disease activity. For instance, both high- based on materials engineering and life sciences [49]. Its (i.e., running) and low- (i.e., walking) intensity aerobic main challenge is to provide an adequate function according exercises appear to be effective in improving functional to the tailored structure. In fact, choosing the right approach status, gait, pain, and aerobic capacity [41]. Moreover, to tissue regeneration is a huge concern for all researchers in resistance training and flexibility exercises are also im- this field. portant, as well as incorporating functional exercises to -e replacement of tissues (such as bone or cartilage) or improve neuromuscular control, balance, and ability to joints with allograft materials includes the risk of infections perform activities of daily living [20]. Although it is well by viruses (such as HIV and hepatitis C), graft vs. host accepted that exercise maintains and improves strength disease [50] or even, chondrocytes can die during the process and aerobic capacity [41], the results available in the lit- [51]. Also, the use of grafts can only be applied to damaged erature are inconclusive. Minimizing or preventing func- areas of less than 2 cm [15]. Accordingly, researchers have tional decline attenuates pain and joint stiffness and aids in been interested in developing alternative approaches for weight control [20, 38, 42]. Still, the development of new restoring joint functionality, which can be translated to investigations (through randomized controlled trials), clinical practice. Although there has been an enormous 4 Journal of Aging Research situ approach with a biopen to repair a full-thickness amount of work with the goal of regenerating cartilage, a personalized construction has not yet been achieved and chondral defect [62] or a 4D bioprinting technology that fabricates dynamic structures improves the cartilage and disseminated. Cartilage has a major role in providing joints with a surface that combines low friction with high lubri- bone regeneration [63, 64]. Undoubtedly, significant efforts cation [52]; thus, a deeper knowledge on cartilage charac- are being developed worldwide in the fields of tissue en- terization, bridging the gap between anatomy and gineering and regenerative medicine, but full osteochondral physiology, may lead the way for better implants aiming restoration remains a paramount challenge; it should not be cartilage repair and regeneration [53]. forgotten that OA is much more than a failure in the car- -e regeneration of articular cartilage resulting from tilage. Total contemplation over osteochondral defects should be considered: anatomy, structure and composition degenerative joint disease, such as OA, is an emerging area under investigation using TE approaches. Recent in- resembling native tissue; biomechanics, ability to yield similar mechanical behavior; and physiology, fully restore vestigations highlighted promising regenerative strategies [37, 54]. For instance, the implantation of an autologous joint functionality [65]. -e different compositions and mechanical properties of bone and cartilage indicate the chondrocytes matrix and the immunization of autologous chondrocytes promise high potential for the regeneration of complexity of this tissue interface, making it challenging for hyaline cartilage [37]. Some strategies are already available the design and fabrication of tissue engineered scaffolds (for on the market and others under investigation: palliative; more details, we have recently published a review on bio- microfracture grafts; cell-based; whole tissue trans- fabrication for osteochondral tissue [4]). plantation; scaffold-based or cell plus scaffold-based; and hydrogels-based or cell plus hydrogel-based. Accordingly, 5. Conclusion we might question that why is OA a burden health problem? OA remains in constant discussion and evolution, as it Probably, because there is a lack of customization on the continues to be a challenging, frustrating, and costly used approaches; because experiments should look for problem. It is not only vital to understand the science behind higher reliability; and because randomized controlled trials the structure and function of articular cartilage components are needed to bridge the gap between the labs and the but also how they interact with risk factors. In this way, clinicians. health professionals should act preventively, with adequate For instance, not long ago, it was reported that most choices of lifestyles for the long-term health of their patient’s commonly used three-dimensional (3D) scaffold architec- joints, as well as contributing to the optimization and tures in cartilage TE were porous 3D sponges [55]. -is customization of treatment by TE. nonconventional procedure does not allow control over the inner architecture, thus, not guaranteeing the desired interconnectivity between pores. Embracing technology Disclosure advancements, TE overcomes some of the mentioned -e content is solely the responsibility of the authors and drawbacks, in particular providing a customized design [56]. does not necessarily represent the views/opinions of any Additive manufacturing (AM), also known as 3D printing, organization. -e present manuscript has not been pub- technologies allow the production of complex 3D structures lished elsewhere or is not being considered for publication with a high level of control, predefined geometry, size, and elsewhere, and the research reported will not be submitted interconnected pores, in a reproducible way [57]. -is for publication elsewhere until a final decision has been controlled organization enhances the vascularization and, made as to its acceptability by the Journal of Aging Research. thus, transport of oxygen and nutrients throughout the whole structure, providing an adequate biomechanical en- vironment for tissue regeneration [58]. -e recent ad- Conflicts of Interest vancements in AM have permitted the design and -e authors declare that they have no conflicts of interest. fabrication of patient-specific scaffolds that possess struc- tural and functional features comparable to the native tissue. Acknowledgments It allows for design and fabrication using tissue images captured with commonly used medical imaging techniques -is research was supported by the European Regional De- such as computer tomography (CT) and magnetic resonance velopment Fund (FEDER), through COMPETE2020 under imaging (MRI) that are readily available in hospitals, the PT2020 program (POCI-01-0145-FEDER-023423), and something that conventional fabrication techniques lack. by the Portuguese Foundation for Science and Technology Recently, hydrogel scaffolds have been developed [59]. (UID/Multi/04044/2019). -ese hydrogels are designed to provide cells with a fully hydrated 3D environment, comparable to the native tissue References extracellular matrix. However, hydrogels have inadequate mechanical properties that are unfavorable for embedded [1] T. M. Griffin and F. 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