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

Pedro Morouço ,1,2 Cristiana Fernandes,3 and Rita Santos-Rocha 2,4

1
Polytechnic Institute of Leiria, School of Education and Social Sciences (ESECS), Leiria, Portugal
2
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
3
Polytechnic Institute of Leiria, Centre for Rapid and Sustainable Product Development (CDRsp), Marinha Grande, Portugal
4
Polytechnic Institute of Santarém, 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. 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.
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.
The 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. Thus, further studies should focus on the impact that exercise (repetitive loading) might
have on cartilage regeneration. Finally, suggestions for future research were proposed.

1. Introduction responding to abnormal (e.g., resistance training) me-

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
instance, due to excessive body mass [1]. Patients frequently
®
(e.g., MaioRegen ) should be enrolled in exercise to de-
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. Thus, 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
Therefore, 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
• Volume • Mechanical loading
• Intensity
Treatment
Physical exercise

Figure 1: Illustrative diagram of the relationships between osteoarthritis, physical exercise, and tissue engineering.

The focus of this manuscript was on the close re- Table 1: Top facts related to OA.
lationship between OA, exercise, and tissue engineering. The (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
scription guidelines, and whether exercise interventions million people worldwide [32]
have a positive effect on OA treatment; and (3) the novel (iii) It is not exclusive for the elderly: more than 50% of adults with
improvements on tissue engineering in the treatment of OA. knee OA are under 65 [30]
(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
Consequences of Osteoarthritis growing trend [34]
(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. The 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
movement with almost zero friction on its surface. The therapeutic choice. Nevertheless, there are known risk
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. Thus, 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. This pathology is associated with
According to the World Health Organization, cartilage- factors such as aging, obesity, nutritional deficiencies, and
related diseases are one of the major societal challenges physical (in)activity; so that, more than 250 million people
(Table 1). The 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]. These 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
absence of an obvious underlying abnormality, secondary in the number of proinflammatory adipocytes and macro-
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].
increase in the age-related fat volume will contribute to OA. The tolerance volume may vary from one day to the next,
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
3 to 4 times after age 50 [23]. However, more recently, due to out 3 times a week [44]. As well as, to maintain healthy
the cotemporaneous lifestyle, the incidence of OA in early joints, a proper balance of the amount and type of exercise is
ages has been increasing [30]. This incidence clearly justifies necessary. The development of structured exercises should
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. This 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
3. Exercise for the Prevention of Osteoarthritis consideration the individual’s disease activity, pain, func-
tional limitations, and personal preferences to optimize
Although mechanical stimulation plays a vital role in adoption and adherence to exercise [20]. Special consider-
maintaining cartilage homeostasis, excessive loading is a ations should include avoiding strenuous exercises during
known contributor to the development of degenerative joint acute flare-ups; advising that small amount of discomfort in
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. That 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].
injury, making it relevant data for prevention [37]. There- Likewise, both patients and practitioners should be
fore, the development of adequate exercise programs for an aware that benefits may come from prescribed and super-
elderly population (a high-risk population) and its massive vised exercise, but also from a more active daily lifestyle
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. The 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 The 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 cm2 [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

amount of work with the goal of regenerating cartilage, a situ approach with a biopen to repair a full-thickness
personalized construction has not yet been achieved and chondral defect [62] or a 4D bioprinting technology that
disseminated. Cartilage has a major role in providing joints fabricates dynamic structures improves the cartilage and
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-
The regeneration of articular cartilage resulting from tilage. Total contemplation over osteochondral defects
degenerative joint disease, such as OA, is an emerging area should be considered: anatomy, structure and composition
under investigation using TE approaches. Recent in- resembling native tissue; biomechanics, ability to yield
vestigations highlighted promising regenerative strategies similar mechanical behavior; and physiology, fully restore
[37, 54]. For instance, the implantation of an autologous joint functionality [65]. The different compositions and
chondrocytes matrix and the immunization of autologous mechanical properties of bone and cartilage indicate the
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?
Probably, because there is a lack of customization on the OA remains in constant discussion and evolution, as it
used approaches; because experiments should look for continues to be a challenging, frustrating, and costly
higher reliability; and because randomized controlled trials problem. It is not only vital to understand the science behind
are needed to bridge the gap between the labs and the the structure and function of articular cartilage components
clinicians. but also how they interact with risk factors. In this way,
For instance, not long ago, it was reported that most health professionals should act preventively, with adequate
commonly used three-dimensional (3D) scaffold architec- choices of lifestyles for the long-term health of their patient’s
tures in cartilage TE were porous 3D sponges [55]. This joints, as well as contributing to the optimization and
nonconventional procedure does not allow control over the customization of treatment by TE.
inner architecture, thus, not guaranteeing the desired
interconnectivity between pores. Embracing technology Disclosure
advancements, TE overcomes some of the mentioned
drawbacks, in particular providing a customized design [56]. The content is solely the responsibility of the authors and
Additive manufacturing (AM), also known as 3D printing, does not necessarily represent the views/opinions of any
technologies allow the production of complex 3D structures organization. The present manuscript has not been pub-
with a high level of control, predefined geometry, size, and lished elsewhere or is not being considered for publication
interconnected pores, in a reproducible way [57]. This elsewhere, and the research reported will not be submitted
controlled organization enhances the vascularization and, for publication elsewhere until a final decision has been
thus, transport of oxygen and nutrients throughout the made as to its acceptability by the Journal of Aging Research.
whole structure, providing an adequate biomechanical en-
vironment for tissue regeneration [58]. The recent ad- Conflicts of Interest
vancements in AM have permitted the design and
fabrication of patient-specific scaffolds that possess struc- The authors declare that they have no conflicts of interest.
tural and functional features comparable to the native tissue.
It allows for design and fabrication using tissue images Acknowledgments
captured with commonly used medical imaging techniques
such as computer tomography (CT) and magnetic resonance This research was supported by the European Regional De-
imaging (MRI) that are readily available in hospitals, velopment Fund (FEDER), through COMPETE2020 under
something that conventional fabrication techniques lack. the PT2020 program (POCI-01-0145-FEDER-023423), and
Recently, hydrogel scaffolds have been developed [59]. by the Portuguese Foundation for Science and Technology
(UID/Multi/04044/2019).
These hydrogels are designed to provide cells with a fully
hydrated 3D environment, comparable to the native tissue
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