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International Journal of Bioprinting Applications of 3D printing in aging

and promoted robust chondrogenesis from mesenchymal in these applications. 3D-printed cartilage is expected to
stem cells with its bionic structures that mimicked natural be the best alternative to cartilage tissue transplantation.
cartilage (Figure 3E). Guan et al. [118] prepared a novel bioink In recent years, significant advancements in the field of
composed of PEGDA, GelMA, and chondroitin sulfate bone and cartilage tissue engineering have been attained,
methacrylate (CSMA) to 3D-print scaffolds for cartilage but these achievements are still far from real-world clinical
tissue regeneration through the use of conventional FDM- applications, likely because engineered tissues usually lack
printed PLA porous scaffolds (Figure 3F). The bioink the kind of spatial complexity of real tissues. 3D printing
was infused into the 3D-printed PLA scaffold to form an has the unique advantage of controlling the volumetric
interpenetrating polymer network with strong mechanical geometry and internal structure of tissue scaffolds, allowing
properties, good biocompatibility, reduced expression of cells to be arranged according to predesigned patterns
osteogenic marker genes, enhanced expression of cartilage- to meet the complexity required for tissue engineering.
specific genes, and deposition of changes in vascular In clinical applications, 3D printing can create specific
endothelial cells with increased glycosaminoglycan (GAG) grafts according to the patient’s needs, reducing the time
levels. and postoperative risks in surgical transplantation. There
has been significant advancement in the development of
Several studies have shown that the conjunction of
electrospun fibers and hydrogels has an important impact on bioinks for the repair of bone and cartilage up to this point.
These inks can facilitate cell proliferation, differentiation,
the enhancement of mechanical properties. Visser et al. [119] and tissue creation, and they are highly printable and
3D printed high-porosity PCL microfiber scaffolds that biocompatible. However, the real-world applications of 3D
were mechanically reinforced with GelMA hydrogels printing in bone and cartilage treatment remain a great
using MEW and showed that the stiffness of the composite challenge as there are many unresolved issues today, such
scaffold was increased compared to hydrogels or microfiber as how to reproduce the regional complexity of natural
scaffolds alone (up to 54-fold), and the reinforced GelMA tissues and how to ensure that a single graft can function
hydrogel had a stress–strain behavior similar to that of properly in a complex bioenvironment. Nevertheless, we
healthy articular cartilage. Furthermore, the rigidity of the believe that 3D printing, with its unique advantages, will
biodegradable polymers was equivalent to that of articular be able to solve these problems and be widely adopted
cartilages in absolute terms, while the mRNA expression of in clinical practice to benefit the aging population with
matrix chondrocyte markers was significantly upregulated orthopedic diseases as research in this field progresses.
in the composite hydrogels. Chen et al. [120] processed
cartilage decellularized matrix (CDM) into a powder 3.3. Cardiovascular system
form and mixed it with hyaluronic acid solution as an ink Cardiovascular disease is the most common disorder
to prepare gelatin/PLGA fibers by DIW. The 3D-printed among the elderly and one of the main causes of death for
CDM-based scaffold’s stiffness and toughness were both those over 65 years old [122] . The prevalence of cardiovascular
increased by the incorporation of fibers. Additionally, disease is as high as 70% in people aged 60–79 years and
the 3D CDM scaffold developed using electrostatically rises to 80% in those aged >80 years [123-125] .
spun fiber reinforcement demonstrated good in vitro
and in vivo biocompatibility and enhanced the repair of 3.3.1. Heart senescence
cartilage injury in rabbit joints. Bas et al. [121] used MEW to The ventricular structure alteration and diastolic
fabricate PCL melt electrospun fiber networks combined dysfunction occur with aging. The significant effects
with star-shaped polyethylene glycol/heparin hydrogels of aging on cardiac structure are characterized as left
(sPEG/Hep) to form hydrogels with mechanical properties ventricular myocardial hypertrophy and left atrial
similar to those of natural cartilage and to provide a proper dilatation, which increase the incidence of heart failure
microenvironment for in vitro chondrocyte culture and and atrial fibrillation. Besides, other degenerative lesions
cartilage formation.
of the aortic valve like aortic calcification, which usually
The application of 3D printing in bone focuses on bone contributes to aortic stenosis, increase with age, reaching
grafting, orthopedic disease treatment, and drug delivery, up to 48% in those older than 84 years old [126] . During
and mainly uses metals, ceramic particles and biopolymers aging, cardiac cells undergo remodeling, mainly in the
as materials. Desired structures are 3D-printed using form of reduced number of ventricular myocytes and sinus
techniques such as powder bed fusion, material extrusion, node pacing cells, which leads to compensatory myocardial
and vat photopolymerization. 3D printing in cartilage hypertrophy. Atrial myocardial fibrosis is closely related
tissue engineering relies more on material extrusion. to the development of atrial fibrillation. In older adults,
Biopolymer, hydrogels, and their composites filled with fibroblast proliferation and collagen deposition in atrial
other functional materials are the commonly used bioinks tissue adversely affect atrial electrophysiology and lower

Volume 9 Issue 4 (2023) 243 https://doi.org/10.18063/ijb.732