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Abstract
Growth plate injuries affecting the pediatric population may cause unwanted bony repair tissue that leads to abnormal bone elongation. Clinical treatment involves bony bar resection and implantation of an interpositional material, but success is limited and the bony bar often reforms. No treatment attempts to regenerate the growth plate cartilage. Herein we develop a 3D printed growth plate mimetic composite as a potential regenerative medicine approach with the goal of preventing limb length discrepancies and inducing cartilage regeneration. A poly(ethylene glycol)-based resin was used with digital light processing to 3D print a mechanical support structure infilled with a soft cartilage-mimetic hydrogel containing chondrogenic cues. Our biomimetic composite has similar mechanical properties to native rabbit growth plate and induced chondrogenic differentiation of rabbit mesenchymal stromal cells in vitro. We evaluated its efficacy as a regenerative interpositional material applied after bony bar resection in a rabbit model of growth plate injury. Radiographic imaging was used to monitor limb length and tibial plateau angle, microcomputed tomography assessed bone morphology, and histology characterized the repair tissue that formed. Our 3D printed growth plate mimetic composite resulted in improved tibial lengthening compared to an untreated control, cartilage-mimetic hydrogel only condition, and a fat graft. However, in vivo the 3D printed growth plate mimetic composite did not show cartilage regeneration within the construct histologically. Nevertheless, this study demonstrates the feasibility of a 3D printed biomimetic composite to improve limb lengthening, a key functional outcome, supporting its further investigation as a treatment for growth plate injuries.
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1 University of Colorado Anschutz Medical Campus, Colorado Program for Musculoskeletal Research, Department of Orthopedics, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X); Shenzhen People’s Hospital (The Second Clinical Medical College Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration, Department of Bone and Joint Surgery, Shenzhen, China (GRID:grid.440218.b) (ISNI:0000 0004 1759 7210)
2 University of Colorado Anschutz Medical Campus, Colorado Program for Musculoskeletal Research, Department of Orthopedics, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X); University of Colorado Boulder, Department of Mechanical Engineering, Boulder, USA (GRID:grid.266190.a) (ISNI:0000000096214564)
3 University of Colorado Boulder, Materials Science and Engineering Program, Boulder, USA (GRID:grid.266190.a) (ISNI:0000000096214564)
4 University of Colorado Anschutz Medical Campus, Colorado Program for Musculoskeletal Research, Department of Orthopedics, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X)
5 University of Colorado Boulder, Department of Mechanical Engineering, Boulder, USA (GRID:grid.266190.a) (ISNI:0000000096214564)
6 National Institute of Standards and Technology (NIST), Applied Chemicals and Materials Division (647), Boulder, USA (GRID:grid.94225.38) (ISNI:000000012158463X)
7 Shenzhen People’s Hospital (The Second Clinical Medical College Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen Key Laboratory of Musculoskeletal Tissue Reconstruction and Function Restoration, Department of Bone and Joint Surgery, Shenzhen, China (GRID:grid.440218.b) (ISNI:0000 0004 1759 7210)
8 University of Colorado Boulder, Materials Science and Engineering Program, Boulder, USA (GRID:grid.266190.a) (ISNI:0000000096214564); University of Colorado Boulder, Department of Electrical, Computer and Energy Engineering, Boulder, USA (GRID:grid.266190.a) (ISNI:0000000096214564)
9 University of Colorado Anschutz Medical Campus, Colorado Program for Musculoskeletal Research, Department of Orthopedics, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X); Children’s Hospital Colorado, Musculoskeletal Research Center, Aurora, USA (GRID:grid.413957.d) (ISNI:0000 0001 0690 7621)
10 University of Colorado Boulder, Department of Mechanical Engineering, Boulder, USA (GRID:grid.266190.a) (ISNI:0000000096214564); University of Colorado Boulder, Materials Science and Engineering Program, Boulder, USA (GRID:grid.266190.a) (ISNI:0000000096214564); University of Colorado Boulder, BioFrontiers Institute, Boulder, USA (GRID:grid.266190.a) (ISNI:0000000096214564)
11 University of Colorado Boulder, Materials Science and Engineering Program, Boulder, USA (GRID:grid.266190.a) (ISNI:0000000096214564); University of Colorado Boulder, BioFrontiers Institute, Boulder, USA (GRID:grid.266190.a) (ISNI:0000000096214564); University of Colorado Boulder, Department of Chemical and Biological Engineering, Boulder, USA (GRID:grid.266190.a) (ISNI:0000000096214564)
12 University of Colorado Anschutz Medical Campus, Colorado Program for Musculoskeletal Research, Department of Orthopedics, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X); University of Colorado Anschutz Medical Campus, Gates Center for Regenerative Medicine, Aurora, USA (GRID:grid.430503.1) (ISNI:0000 0001 0703 675X)