Reduced osseointegration in disuse and denervation rat models results from impaired cellular responses to multiscale microstructured titanium surfaces

Jingyao Deng; David Joshua Cohen; Enrique B Matias; Lucas O Olson; Michael J McClure; Barbara D Boyan; Zvi Schwartz

doi:10.1002/jor.25843

Reduced osseointegration in disuse and denervation rat models results from impaired cellular responses to multiscale microstructured titanium surfaces

J Orthop Res. 2024 Apr 21. doi: 10.1002/jor.25843. Online ahead of print.

Authors

Jingyao Deng¹, David Joshua Cohen¹, Enrique B Matias¹, Lucas O Olson¹, Michael J McClure¹, Barbara D Boyan^{1

2}, Zvi Schwartz^{1

3}

Affiliations

¹ Department of Biomedical Engineering, College of Engineering, Virginia Commonwealth University, Richmond, Virginia, USA.
² Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA.
³ Department of Periodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.

PMID: 38644051
DOI: 10.1002/jor.25843

Abstract

Immobilization-induced skeletal unloading results in muscle atrophy and rapid bone loss, thereby increasing the risk of falling and the need for implant therapy in patients with extended bed rest or neuromuscular injuries. Skeletal unloading causes bone loss by altering bone growth and resorption, suggesting that implant performance might be affected. To test this, we focused on early events in implant osseointegration. We used the rat sciatic neurectomy-induced disuse model under two different settings. In Study 1, 16 Sprague Dawley rats (SD) were separated into control, sham operated+cast immobilization, and sciatic neurectomy+casting groups; titanium implants with multiscale microtextured topography and hydrophilic chemistry (modSLA) were inserted in the distal femoral metaphysis. Neurectomy surgeries and casting were performed at the same surgical setting as implant placement; rats were euthanized 4 weeks post-implantation. In Study 2, we established the unloaded condition before implantation. A total of 12 SD rats were divided into control and sciatic+femoral neurectomy groups. A total of 24 days after sciatic and femoral neurectomy surgery, rats received implants. Study 2 rats were euthanized at 4 weeks post-implantation. MicroCT and histomorphometry showed that trabecular bone and osseointegration were reduced when disuse was established before implantation. Osteoblasts isolated from Study 1 sciatic neurectomy tibial bones exhibited impaired differentiation on modSLA culture disks, revealing a possible mechanism responsible for the decreased osseointegration observed in the Study 2 rats. This study addressed the importance of considering the mechanical unloading and muscle function history before implant insertion and suggests that implant performance was reduced due to poor cellular ability to regenerate.

Keywords: denervation; disuse atrophy; microstructured titanium implants; osseointegration; osteoblast differentiation.

Grants and funding

R01AR072500/AR/NIAMS NIH HHS/United States