Multiphasic bone-ligament-bone integrated scaffold enhances ligamentization and graft-bone integration after anterior cruciate ligament reconstruction

Xianrui Xie; Jiangyu Cai; Dan Li; Yujie Chen; Chunhua Wang; Guige Hou; Thorsten Steinberg; Bernd Rolauffs; Mohamed El-Newehy; Hany El-Hamshary; Jia Jiang; Xiumei Mo; Jinzhong Zhao; Jinglei Wu

doi:10.1016/j.bioactmat.2023.08.004

Multiphasic bone-ligament-bone integrated scaffold enhances ligamentization and graft-bone integration after anterior cruciate ligament reconstruction

Bioact Mater. 2023 Aug 12:31:178-191. doi: 10.1016/j.bioactmat.2023.08.004. eCollection 2024 Jan.

Authors

Xianrui Xie^{1

2}, Jiangyu Cai^{3

4}, Dan Li¹, Yujie Chen¹, Chunhua Wang², Guige Hou², Thorsten Steinberg⁵, Bernd Rolauffs⁶, Mohamed El-Newehy⁷, Hany El-Hamshary⁷, Jia Jiang³, Xiumei Mo^{1

2}, Jinzhong Zhao³, Jinglei Wu^{1

2}

Affiliations

¹ State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, 201620, PR China.
² School of Pharmacy, Key Laboratory of Prescription Effect and Clinical Evaluation of State Administration of Traditional Chinese Medicine of China, Binzhou Medical University, Yantai, 264003, China.
³ Department of Sports Medicine, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
⁴ National Engineering Laboratory for Modern Silk, Soochow University, Suzhou, 215123, China.
⁵ Division of Oral Biotechnology, Center for Dental Medicine, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.
⁶ G.E.R.N. Research Center for Tissue Replacement, Regeneration & Neogenesis, Department of Orthopedics and Trauma Surgery, Faculty of Medicine, Medical Center-Albert-Ludwigs-University of Freiburg, 79085, Freiburg im Breisgau, Germany.
⁷ Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia.

Abstract

The escalating prevalence of anterior cruciate ligament (ACL) injuries in sports necessitates innovative strategies for ACL reconstruction. In this study, we propose a multiphasic bone-ligament-bone (BLB) integrated scaffold as a potential solution. The BLB scaffold comprised two polylactic acid (PLA)/deferoxamine (DFO)@mesoporous hydroxyapatite (MHA) thermally induced phase separation (TIPS) scaffolds bridged by silk fibroin (SF)/connective tissue growth factor (CTGF)@Poly(l-lactide-co-ε-caprolactone) (PLCL) nanofiber yarn braided scaffold. This combination mimics the native architecture of the ACL tissue. The mechanical properties of the BLB scaffolds were determined to be compatible with the human ACL. In vitro experiments demonstrated that CTGF induced the expression of ligament-related genes, while TIPS scaffolds loaded with MHA and DFO enhanced the osteogenic-related gene expression of bone marrow stem cells (BMSCs) and promoted the migration and tubular formation of human umbilical vein endothelial cells (HUVECs). In rabbit models, the BLB scaffold efficiently facilitated ligamentization and graft-bone integration processes by providing bioactive substances. The double delivery of DFO and calcium ions by the BLB scaffold synergistically promoted bone regeneration, while CTGF improved collagen formation and ligament healing. Collectively, the findings indicate that the BLB scaffold exhibits substantial promise for ACL reconstruction. Additional investigation and advancement of this scaffold may yield enhanced results in the management of ACL injuries.

Keywords: Anterior cruciate ligament reconstruction; Electrospun; Graft-bone integration; Integrated scaffold; Thermally induced phase separation.