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Review
. 2021 Mar 10;13(2):10.1088/1758-5090/abc8de.
doi: 10.1088/1758-5090/abc8de.

Recent advances in 3D bioprinting of musculoskeletal tissues

Tyler Potyondy  1   2   3 , Jorge Alfredo Uquillas  4 , Peyton J Tebon  1   2 , Batzaya Byambaa  5   6 , Anwarul Hasan  7   8 , Maryam Tavafoghi  1   2 , Heloise Mary  1   9 , George E Aninwene 2nd  1   2   10 , Ippokratis Pountos  11   12 , Ali Khademhosseini  1   2   13   14   15 , Nureddin Ashammakhi  1   2   3   13   16
Affiliations
Review

Recent advances in 3D bioprinting of musculoskeletal tissues

Tyler Potyondy et al. Biofabrication. .

Abstract

The musculoskeletal system is essential for maintaining posture, protecting organs, facilitating locomotion, and regulating various cellular and metabolic functions. Injury to this system due to trauma or wear is common, and severe damage may require surgery to restore function and prevent further harm. Autografts are the current gold standard for the replacement of lost or damaged tissues. However, these grafts are constrained by limited supply and donor site morbidity. Allografts, xenografts, and alloplastic materials represent viable alternatives, but each of these methods also has its own problems and limitations. Technological advances in three-dimensional (3D) printing and its biomedical adaptation, 3D bioprinting, have the potential to provide viable, autologous tissue-like constructs that can be used to repair musculoskeletal defects. Though bioprinting is currently unable to develop mature, implantable tissues, it can pattern cells in 3D constructs with features facilitating maturation and vascularization. Further advances in the field may enable the manufacture of constructs that can mimic native tissues in complexity, spatial heterogeneity, and ultimately, clinical utility. This review studies the use of 3D bioprinting for engineering bone, cartilage, muscle, tendon, ligament, and their interface tissues. Additionally, the current limitations and challenges in the field are discussed and the prospects for future progress are highlighted.

Keywords: 3D bioprinting; bone; graft; musculoskeletal; tissue defects; tissue engineering.

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Figures

Figure 1.
Figure 1.
Schematic illustration of the materials and techniques used for the bioprinting of musculoskeletal tissues and their interface. Polycaprolactone (PCL), poly(lactide-co-glycolide) (PLGA), Mesenchymal stem cells (MSCs), Poly(ethylene glycol) Diacrylate (PEGDA), Bone marrow derived Mesenchymal stem cells (BM-MSCs), Embryonic stem cells (ESCs), Induced pluripotent stem cells (iPSCs), Human umbilical vein endothelial cells (HUVECs), Adipose-derived stem cells (ADSCs), Polyethylene glycol (PEG), Hyaluronic acid (HA), Mouse-derived stem cells (MDSC), Polyglycolide (PGA), Photosensitive polyurethane (PU), Gelatin methacryloyl (GelMA), Polylactide (PLA) , and Acrylonitrile butadiene styrene (ABS).
Figure 2.
Figure 2.
The three most common 3D bioprinting techniques: (A) microextrusion (consisting of pneumatic, piston-based, and screw-based) (B) inkjet (consisting of thermal and piezoelectric), and (C) laser-assisted bioprinting. Adapted from Pountos et al. [28] with permission from Springer.
Figure 3.
Figure 3.. Integrated tissue-organ printer (ITOP) for bone construct:
A) Schematic illustration of ITOP system and patterning of 3D structure consisting of multiple cell-laden hydrogels and PCL polymer. B) Three different images and visualizations of the two types of constructs created. Moving from left to right: a computer visualization of the printed construct, images taken of the printed construct from varying perspectives, and a fluorescent image (3T3’s were labeled with a red and green dye respectively). C) Computer visualization of printing pattern for 3D printing a calvarial bone construct (top). Image of printed calvarial bone construct (bottom). D) Scanning Electron Microscope (SEM) image of calvarial bone construct. E) Image of calvarial printed construct day 0 (top) and five months after implantation (bottom). Reproduced from Kang et al. [11] with permission from Nature Publishing Group.
Figure 4.
Figure 4.
3D bioprinting of cartilage: A) Bioprinting of chondrocyte-laden GelMA with (iii and iv) or without (i ad ii) HA. Addition of HA resulted in the continuous flow of bioink that allowed for the printing of a multi-layered structure (iv). B) Hybrid bioprinting of GelMA/HA resulted in the formation of two distinct phases of hydrogels labeled in blue and orange. Adapted from Schuurman et al. [100] with permission from Wiley-VCH. C) Schematic illustration of a coaxial printhead screwed to the 3D-Bioplotter. D) Optical images of MSC-loaded Alginate/GelMA/CS-AEMA/HAMA composite hydrogels printed using the coaxial system. Adapted from Costantini et al. [101] with permission from IOP Publishing. E) 3D printed structures based on chondrocyte-laden methacrylated polyHPMA-lac-PEG and HAMA hydrogels. Adapted from Abbadessa et al. [99] with permission from American Chemical Society. F) Images showing articular cartilage scaffolds based on MSC-loaded photosensitive PU and HAp printed using DLP technique. Reproduced from Shie et al. [86], with permission from MDPI.
Figure 5.
Figure 5.. Bioprinting of muscle and tendon:
A) Schematic showing the 3D printing of muscle construct using myoblast-laden mdECM bioink (i). Immunofluorescent images of 3D printed myotubes, MHC is stained in green and the nuclei are stained in blue. The white arrows indicate alignment of muscle fibers (ii). Morphometric analysis of myotubes including, length, myotube width, fusion index, and myotube area (iii). Adapted from Choi et al. [115] with permission from Wiley-VCH. B) 3D printed muscle model based on GelMA/PEGDMA hydrogel loaded with SkMDCs. MHC staining confirms the myogenic activity of SkMDCs cultured for 9 days. MHC is stained in green and the cell nuclei in red. C) Tendon model based on tenocyte-laden GelMA/PEGDMA hydrogel stained for collagen type I (I and ii) or III (iii and iv) on day 9 of culture. Collagen type I and III are stained in green and cell nuclei in red. Reproduced from Laternser et al. [117] with permission from Society for Laboratory Automation and Screening.
Figure 6.
Figure 6.
Images from bioprinted osteochondral construct and rabbit in vivo trial. A) Schematic illustration of the multi head tissue/organ building system (MtoBS) used for 3D printing of MSCs loaded ECM/PCL composite hydrogels resulting in the fabrication of multilayered 3D construct for regeneration of osteochondral tissue. B) Image of rabbit prior to simulating osteochondral injury (i), simulated osteochondral defect in rabbit knee joint (ii), and implantation of 3D Bioprinted osteochondral construct (iii). C) Schematic illustration of experimental groups for the in vivo experiment. D) Images showing bone (group 1) and cartilage (group 2) like tissue regeneration in the samples after implantation for 8 weeks. Reproduced from Shim et al. with permission from IOP Publishing.
Figure 7.
Figure 7.. Bioprinting of muscle/tendon interface tissue:
A) Schematic illustration of 3D integrated organ printing (IOP). B) 3D printed muscle/tendon unit using IOP system. C) Tensile properties of the bioprinted muscle/tendon unit. Representative tensile-strain curves (i-iii), Young’s modulus (iv), tensile strength (v), and failure strain (vi). D) Fluorescence images (i-iii) of C2C12 and 3T3 cells labeled with DiO (green) and DiI (red), respectively, on day 7 of culture. Yellow shows the interface between green and red fluorescence. Immunofluorescence staining of 3D printed muscle/tendon units (iv-vii) on the muscle side (iv nd v) showing highly aligned myotubes, at the interface (vi), and on the tendon side (vii) showing the secretion of collagen type I. Desmin (iv, vi) and MHC (v) were stain in red. Collagen type I was stained in green and the cell nuclei in blue. Reproduced from Merceron et al. [23] with permission from IOP publishing.
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References

    1. Christensen LV, Physiology and pathophysiology of skeletal muscle contractions. Part II. Static activity, Journal of oral rehabilitation, 13 (1986) 463–477. - PubMed
    1. Christensen LV, Physiology and pathophysiology of skeletal muscle contractions. Part I. Dynamic activity, Journal of oral rehabilitation, 13 (1986) 451–461. - PubMed
    1. Xu Y, Murrell GAC, The Basic Science of Tendinopathy, Clinical orthopaedics and related research, 466 (2008) 1528–1538. - PMC - PubMed
    1. Gobbi A, Francisco RA, Lubowitz JH, Allegra F, Canata G, Osteochondral Lesions of the Talus: Randomized Controlled Trial Comparing Chondroplasty, Microfracture, and Osteochondral Autograft Transplantation, Arthroscopy: The Journal of Arthroscopic & Related Surgery, 22 (2006) 1085–1092. - PubMed
    1. Jackson DW, Grood ES, Goldstein JD, Rosen MA, Kurzweil PR, Cummings JF, Simon TM, A comparison of patellar tendon autograft and allograft used for anterior cruciate ligament reconstruction in the goat model, The American Journal of Sports Medicine, 21 (1993) 176–185. - PubMed

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