The Design and Characterization of a Strong Bio-Ink for Meniscus Regeneration

Abstract

The meniscus is vital to the mechanical function of the knee, while it is frequently harmed because it bears a heavy load. A strong bio-ink for meniscus regeneration was prepared for the future meniscal tissue engineering. The prepared bio-ink consists of poly (vinyl alcohol) and decellularized extracellular matrix (PVA/dECM). The mechanical properties and the rheological features were explored to evaluate the effects of freezing/thawing cycles and alkaline treatment process. The printability was verified using a three-dimensional printer. The endothelial cells were employed to assess the biocompatibility. Finally, a 12-week rabbit meniscus defect model was established to evaluate the meniscus regeneration capability. We found that the bio-ink by soaking in alkaline for 40 min and 20 freezing/thawing cycles demonstrated excellent mechanical properties. The Young’s modulus reached 0.49 MPa and the stress limitation was 2.9 MPa. The results also showed good printability and biocompatibility of the proposed bio-ink in vitro. The PVA/dECM hydrogel healed the meniscus defect after 12 weeks of implantation. The articular cartilage and subchondral bone exhibited normal microstructure and composition. These results suggested that the PVA/dECM hydrogel could be a promising solution to repair meniscal lesions with preventive effects against degenerative meniscal tears and post-traumatic arthritis.

Role of hydrogels in osteoarthritis: A comprehensive review

“…For poly (vinyl alcohol)-based hydrogels, administration of PVA/dECM hydrogel to parapatellar incision-induced disclosed lateral meniscus will repair the meniscus defects, as evidenced by a covered glossy and smooth meniscus, more regeneration area of the meniscus, and increased expression of collagen II. 10 This was confirmed in OA patients with first carpometacarpal joints, where the patients treated with poly (vinyl alcohol) hydrogel reported low Disabilities of Arm Shoulder Hand scores, Visual Analog Scale scores, improved grip/pinch strength, as well as no radiographic evidence of osteolysis. 58 For poly(ethylene glycol)based hydrogels, injection of ECM and polyethylene glycol diacrylate together with natural compound honokiol (PEGDA/ECM/Hon) hydrogel into osteochondral defects in the patellar groove was able to improve International Cartilage Repair Society (ICRS) scores, and repair cartilage, as evidenced by the much calcified tissue generated, increased ratio of BV/TV, and surfaces of the defects filled with hyaline cartilage-like tissue.…”

“…When IL‐1β‐stimulated chondrocytes were treated with MET@DSH hydrogel or epigallocatechin‐3‐gallate (EGCG) conjugated hyaluronic acid and gelatin hydrogel (EGCG‐HA/Gelatin), levels of anabolism markers (collagen II, aggrecan, sry‐box transcription factor 9 (SOX9), disintegrin, and metalloprotease with thrombospondin motifs 5 (ADAMTS5)) were increased, and catabolic markers (matrix metalloproteinase 3 (MMP‐3), MMP‐13) were decreased 5,9 . Human umbilical vein endothelial cells (HUVECs) were cultured on the surface of a poly (vinyl alcohol) and decellularized extracellular matrix (PVA/dECM) hydrogel, showing obvious adhesion morphology and amounts of living cells 10 . Most of the KGN/Dex‐TSPBA@WHMs hydrogel‐treated ATDC5 cells were viable, along with elevated cell density, and bone marrow mesenchymal stem cells (BMSCs) treated with KGN/Dex‐TSPBA@WHMs hydrogel revealed upregulated expression of collagen II 7 .…”

“…On the contrary, treatment of papain‐induced OA rabbits with glucosamine‐loaded hydrogels based on poloxamers significantly inhibited joint swelling and inflammatory factor expression. For poly (vinyl alcohol)‐based hydrogels, administration of PVA/dECM hydrogel to parapatellar incision‐induced disclosed lateral meniscus will repair the meniscus defects, as evidenced by a covered glossy and smooth meniscus, more regeneration area of the meniscus, and increased expression of collagen II 10 . This was confirmed in OA patients with first carpometacarpal joints, where the patients treated with poly (vinyl alcohol) hydrogel reported low Disabilities of Arm Shoulder Hand scores, Visual Analog Scale scores, improved grip/pinch strength, as well as no radiographic evidence of osteolysis 58 .…”

“…5,9 Human umbilical vein endothelial cells (HUVECs) were cultured on the surface of a poly (vinyl alcohol) and decellularized extracellular matrix (PVA/dECM) hydrogel, showing obvious adhesion morphology and amounts of living cells. 10 Most of the KGN/ Dex-TSPBA@WHMs hydrogel-treated ATDC5 cells were viable, along with elevated cell density, and bone marrow mesenchymal stem cells (BMSCs) treated with KGN/Dex-TSPBA@WHMs hydrogel revealed upregulated expression of collagen II. 7 Human articular chondrocytes and monkey articular chondrocytes were cultivated with an IEIK13 self-assembling peptide hydrogel, showing enhanced expression of collagen II and aggrecan.…”

Dual Crosslinked Antioxidant Mixture of Poly(vinyl alcohol) and Cerium Oxide Nanoparticles as a Bioink for 3D Bioprinting

“…Crosslinking restricts the mobility of polymeric chains, thus affecting the chemical structure and crystallinity of the polymer. Furthermore, in the case of PVA, crosslinking has been shown to enhance cell adhesion by forming hydrogen bonds between the polar groups that exist on the cell surface and the hydroxyl groups of the polymer. − One advantage of using PVA is the possibility of partial crosslinking by utilizing a portion of the hydroxyl groups present on the polymer backbone, thereby enabling further modification of the remaining hydroxyl groups. These remaining groups can then be utilized to introduce additional functionalities. , …”