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A strong bio-ink for Meniscus Regeneration
homeostasis, biomechanics, and structural stability. of processed dECM scaffolds in biomechanics and to
Meniscus injury is very common in middle-aged and repair meniscus deficiency in vivo.
older adults. Knee discomfort and even reduced mobility Traditional techniques, such as freeze-thawing
are the most common symptoms of meniscal damage. and chemical crosslinking, have been utilized to create
The outcomes of case studies from the 1940s on partial hydrogels from poly (vinyl alcohol) (PVA) . PVA
[17]
regeneration of peripheral meniscal tissue following scaffolds showed high mechanical properties and
complete meniscectomy had bolstered our belief that cytocompatibility, promoting regeneration of different
radical excision would result in a better outcome than tissues [18-21] . Under freeze-thaw cycles, Parameswaran-
repair. However, a number of studies with a 10 – 20-year Thankam et al. created bionanocomposite hydrogels
follow-up period following complete meniscectomy have by combining HPG, PVA, and nano-hydroxyapatite,
been conducted. Following the operation, these trials all and osteoblastic activity was demonstrated in vitro .
[21]
showed an unacceptably high prevalence of radiographic Thankam et al. used PVA to shape the rotator cuff ligament
knee osteoarthritis (OA), knee pain, and impaired and shown its potential for use in the treatment of rotator
knee function [2-8] . Roos et al. reported that the risk of cuff tendon injuries . Therefore, a PVA hydrogel can
[19]
developing radiographic tibiofemoral OA was elevated mimic the mechanical properties of meniscus at some
six-fold at 21 years after total meniscectomy (relative aspects, and it can be regarded as a candidate for the
risk: 6.4; 95% confidence interval: 2.7 – 15.2) . The meniscus tissue engineering.
[9]
meniscus is widely known for having a restricted ability In addition, the photocrosslinked system may be
for tissue regeneration. Only the peripheral vascularized advantageous to achieve a better gelling capability in the
section of damaged adult menisci heals on its own, but the bio-ink. One of the most common procedures for fabricating
interior avascular area hardly heals on its own . Thus, biomaterials is free-radical photopolymerization, which
[10]
promoting the meniscal repair has noticeably attracted has various benefits, including relatively high reaction
surgeons’ attention. rates at room temperature, spatial and temporal control of
Decellularized extracellular matrix (dECM) the initiation process, minimal energy input, and chemical
scaffolds have been studied as a natural substitute for diversity. The photocrosslinked system has been applied
the torn meniscus, which is claimed to have the potential in a variety of polymers, including poly (ethylene glycol)
to stimulate regeneration. dECM scaffolds may also be (PEG) gelatin methacryloyl, and methacryloyl hyaluronic
constructed by extracting cells and components from acid [22-25] . PEG hydrogels have been used in drug delivery,
allogeneic or xenogeneic donor tissues. Physical (e.g., wound healing, and a variety of biomedical applications
shocks and freeze-thaw cycles), chemical (e.g., detergents due to its beneficial qualities such as non-toxicity, strong
like Triton X-100 and sodium dodecyl sulfate [SDS]), water solubility, biocompatibility, and highly adjustable
and enzymatic (e.g., DNase and trypsin) therapies capabilities. Changing the monomer (e.g., PEG
damage and solubilize the cell’s cytoplasmic and nuclear methacrylate, PEG acrylic amide, vinyl alcohol, methyl
membranes. [11-15] . The obtained dECM scaffolds showed methacrylate, and methacrylic acid) can positively tailor
excellent biomechanical properties and a minimum the crosslinking density of PEG hydrogels to satisfy
immunogenicity. Then, by recreating a similar tissue varied demands [22,23] .
milieu to encourage cell infiltration and ECM formation, In the present study, we designed a PVA/dECM
the dECM scaffolds were employed to repair injured bio-ink for three-dimensional (3D) printing of meniscal
menisci in the knee joint. The fibrous structure of dECM scaffolds. The proposed bio-ink formed hydrogels under
meniscus tissue, on the other hand, was thick and dense, photocrosslinking to mimic the mechanical properties of
making cell infiltration into the inner area of the implanted meniscus. The PVA could form a strong and stretchable
scaffolds challenging. Wu et al. converted acellular network through freezing/thawing and alkaline treating
scaffolds into hydrogels, resulting in greater porosity and process. The alginate chains formed the ionic networks,
fast cell infiltration in the implanted material . When the PEG diacrylate (PEGDA) chains formed the covalent
[16]
compared to intact dECM meniscal scaffolds, processed bond networks, and the dECM provided the necessary
dECM meniscal scaffolds, such as meniscal slices, bioactive factors for meniscus tissue regeneration. This
powders, and hydrogels, may attain greater success in strategy could realize the fabrication of PVA/dECM
cell regeneration. The loss of the original structure of hydrogel scaffolds with high mechanical properties,
the processed dECM meniscal scaffolds could result in being resistant to injury, and with properties of shape
biomechanical disadvantages that may impact cellular memory polymers. Concurrently, the PVA/dECM bio-
behavior and metabolic activity in vivo. Therefore, the ink simulated a natural tissue microenvironment to
application of processed dECM meniscus was limited to promote meniscal repair. The PVA/dECM bio-ink can be
the partial meniscus regeneration. Further studies should an ideal candidate for 3D printing and meniscus tissue
be therefore conducted to assess the regenerative capacity regeneration.

32 International Journal of Bioprinting (2022)–Volume 8, Issue 4