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International Journal of Bioprinting 3D cartilage induction and monitoring

1. Introduction to autologous cells, facilitating the synthesis of their
matrix components. This unique characteristic enables
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Regenerative medicine (RM) aims to restore or establish the in vitro cultivation of tissue, closely mimicking the
normal function by entirely or partially regenerating biochemical integrity of healthy AC. The presence of
human cells, organs, or tissues. Living cells, biomaterials, the matrix surrounding the cells has been observed to
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and bioactive cues are the three pillars of tissue engineering augment donor cell retention and confer protection
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(TE), a subset of RM. Among the various illnesses that against inflammatory agents. 21
can benefit from the advances in TE is osteoarthritis
(OA), an incurable and complex disorder. The pathogenic Moreover, these scaffolds fulfill several essential
process leading to OA is characterized by persistent low- criteria: (i) they possess an appropriate surface with
grade articular cartilage (AC) deterioration, which is requisite roughness and hydrophilicity, enhancing cell
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the primary cause of continuous joint degeneration. As adhesion, (ii) they exhibit an internal structure comprising
such, OA should not be regarded as a disease but rather porosity, pore size (PS), and fiber diameter, conducive
as the common endpoint of several secondary pathways to cellular adherence, proliferation, differentiation, as
associated with age, possible traumas, obesity, and the well as facilitating the diffusion of nutrients, oxygen, and
resulting changes in the biomechanics of the joint. As AC waste products, (iii) they demonstrate mechanical and
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is an avascular tissue with no lymphatic system and nerve biochemical properties akin to the target tissue. The
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endings, OA patients have a limited regeneration rate, utilization of 3D printing methodologies with biopolymers
making TE an accurate tool to revert OA with techniques for scaffold fabrication has transformed TE. Recent
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such as biofabrication. Due to the loss of AC, OA causes investigations reveal that orthopedic implants crafted
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pain and loss of joint function. No known treatment for from polyetheretherketone (PEEK) filaments reinforced
OA can stop or decrease its progression; surgical treatments with internal TiO nanoparticles manifest significantly
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are the go-to option. Numerous TE based-products and heightened mechanical strength compared to conventional
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treatments have attempted to simulate AC over the past few materials. Concurrently, polylactic acid (PLA)-based
decades (some of them are still in clinical trials), including artificial bone grafts exhibit commendable mechanical
autologous chondrocyte implantation (ACI), the matrix- properties and promote cell growth and differentiation. 24
associated autologous chondrocyte implantation (MACI), Concerning AC, one of these promising new biomaterials
NeoCart®, NOVOCART® 3D, Cartipatch®, and Spherox, 8–10 is 1,4-butanediol thermoplastic polyurethane (bTPUe),
among others. However, clinical surgical treatments, such which is a promising TE target for OA. Despite this, it is
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as ACI or MACI, lack long-term effectiveness. Another crucial to ensure adequate cell–biomaterial interaction for
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example is mosaicplasty, a treatment for focal chondral reducing the synthetic polymers’ hydrophobic behavior.
lesions, which reported relatively acceptable results for the This can be attained with surface modifications, such
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first 2 years but failed thereafter (≈55%). 12 as with Arg-Gly-Asp (RGD) peptides, 1-pyrene butyric
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A mechanical derangement that causes low-grade injury acid (PBA), or various ECM elements, like fibronectin
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to the AC is the primary driver in the development of OA. or collagen. 29
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As a result, three distinct stages may be identified from a Mesenchymal stem cells (MSCs) can develop into
biomechanical perspective: (i) the proteolytic breakdown the chondrogenic lineage and have a high rate of
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of the extracellular matrix (ECM) of AC, (ii) the fibrillation in vitro proliferation while retaining their capacity
and erosion of the AC surface, and (iii) the onset of for multipotent differentiation, making them pretty
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synovial inflammation. A typical mechanical stimulation attractive as therapeutic agents. The infrapatellar fat
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for AC is mechanical loads, described as direct interactions pad (IPFP) is one of the sites from which multipotent
between two surfaces in the form of stress, varying from cells can be isolated; therefore, IPFP-MSCs are a reliable
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0.5 to 8 MPa. On the other hand, frictional loads, exerted cell source for AC TE. Previously, it was demonstrated
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by interstitial fluid, increase cartilage liquid pressurization, that biomechanical stimulation induces chondrogenesis
inducing hydrostatic pressures; this contributes to the from MSCs by phosphorylation of Sox9 through protein
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increase in AC stiffness under dynamic stress. However, kinase A (PKA), cAMP, Ser133, and CREB. 35,36 Hence,
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solid ECM sustains the remaining proportion (66%) of the any pathway that involves the transmission of signals
compression load. Given the crucial role of mechanical from mechanical stimulation to electrochemical activity
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factors in OA, TE techniques, such as three dimensional is called mechanotransduction. The mechanosensory
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(3D) printing, are being explored for its treatment.
transient receptor potential vanilloid 4 (TRPV4), piezo 1,
3D matrices, commonly known as scaffolds, are integral and piezo 2 are found in chondrocytes and osteoblasts—
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components in biopolymer 3D printing methodologies. bone and cartilage tissue exhibit acute mechanosensitivity
These scaffolds provide transient structural support to maintain homeostasis. For example, osteoporosis is
Volume 10 Issue 4 (2024) 367 doi: 10.36922/ijb.3389