The efficiency of genetically modified mesenchymal stromal cells combined with a functionally graded scaffold for bone regeneration in corticosteroid‐induced osteonecrosis of the femoral head in rabbits

Author:

Tsubosaka Masanori1ORCID,Maruyama Masahiro1,Lui Elaine1,Moeinzadeh Seyedsina1,Huang Elijah Ejun1,Kushioka Junichi1,Hirata Hirohito1,Jain Charu1,Storaci Hunter W.1,Chan Calvin1,Toya Masakazu1,Gao Qi1,Teissier Victoria1,Shen Huaishuang1,Li Xueping1,Zhang Ning1,Matsumoto Tomoyuki2,Kuroda Ryosuke2,Goodman Stuart B.13ORCID,Yang Yunzhi Peter134ORCID

Affiliation:

1. Department of Orthopaedic Surgery Stanford University School of Medicine Stanford California USA

2. Department of Orthopaedic Surgery Kobe University Graduate School of Medicine Kobe Hyogo Japan

3. Department of Bioengineering Stanford University School of Medicine Stanford California USA

4. Department of Material Science and Engineering Stanford University School of Medicine Stanford California USA

Abstract

AbstractCore decompression (CD) with mesenchymal stromal cells (MSCs) is an effective therapy for early‐stage osteonecrosis of the femoral head (ONFH). Preconditioning of MSCs, using inflammatory mediators, is widely used in immunology and various cell therapies. We developed a three‐dimensional printed functionally graded scaffold (FGS), made of β‐TCP and PCL, for cell delivery at a specific location. The present study examined the efficacy of CD treatments with genetically modified (GM) MSCs over‐expressing PDGF‐BB (PDGF‐MSCs) or GM MSCs co‐over‐expressing IL‐4 and PDGF‐BB and preconditioned for three days of exposure to lipopolysaccharide and tumor necrosis factor‐alpha (IL‐4‐PDGF‐pMSCs) using the FGS for treating steroid‐induced ONFH in rabbits. We compared CD without cell‐therapy, with IL‐4‐PDGF‐pMSCs alone, and with FGS loaded with PDGF‐MSCs or IL‐4‐PDGF‐pMSCs. For the area inside the CD, the bone volume in the CD alone was higher than in both FGS groups. The IL‐4‐PDGF‐pMSCs alone and FGS + PDGF‐MSCs reduced the occurrence of empty lacunae and improved osteoclastogenesis. There was no significant difference in angiogenesis among the four groups. The combined effect of GM MSCs or pMSCs and the FGS was not superior to the effect of each alone. To establish an important adjunctive therapy for CD for early ONFH in the future, it is necessary and essential to develop an FGS that delivers biologics appropriately and provides structural and mechanical support.

Funder

National Institute of Arthritis and Musculoskeletal and Skin Diseases

Publisher

Wiley

Subject

Metals and Alloys,Biomedical Engineering,Biomaterials,Ceramics and Composites

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