Agili-C implant promotes the regenerative capacity of articular cartilage defects in an ex vivo model
Osteochondral implants are currently adopted for the treatment of symptomatic full-thickness chondral and osteochondral defects. Agili-C™ is a cell-free aragonite-based scaffold which aims to reproduce the original structure and function of the articular joint while directing the growth and regeneration of both cartilage and its underlying subchondral bone. The goal of the present study was to investigate the ex vivo mechanisms of action (MOA) of the Agili-C™ implant in the repair of full-thickness cartilage defects. In particular, we tested whether Agili-C™ implant has the potential to stimulate cartilage ingrowth through chondrocytes migration into the 3D interconnected porous structure of the scaffold, along with maintaining their viability and phenotype and the deposition of hyaline cartilage matrix.
Articular cartilage samples were collected through the Gift of Hope Organ and Tissue Donor Network (Itasca, IL) within 24 h from death. For this study, cartilage from a total of 14 donors was used. To model a chondral defect, donut-shaped cartilage explants were prepared from each tissue specimen. The chondral phase of the Agili-C™ implant was placed inside the tissue in full contact and press fit manner. Cartilage explants with the Agili-C™ implant inside were cultured for 60 days. As a control, the same donut-shaped cartilage explants were cultured without Agili-C™, under the same culture conditions.
Using fresh human cadaveric articular cartilage tissue in a 60-day culture, it was demonstrated that chondrocytes were able to migrate into the Agili-C™ scaffold and contribute to the deposition of the extracellular matrix (ECM) rich in collagen type II and aggrecan, and lacking collagen type I. Additionally, we were able to show the formation of a layer populated by progenitor-like cells on the articular surface of the implant.
The analysis of samples taken from knee and ankle joints of human donors with a wide age range and both genders supports the potential of Agili-C™ scaffold to stimulate cartilage regeneration and repair. Based on these results, the present scaffold can be used in the clinical practice as a one-step procedure to treat full-thickness chondral defects.
KeywordsChondral defect Scaffold Biomaterial Aragonite Cartilage regeneration Ex vivo study
The authors would like to acknowledge the Gift of Hope Organ and Tissue Donor Network and donor’s family for human tissue donation. We also would like to acknowledge the personnel from the laboratory of Dr. Chubinskaya: Dr.Arkady Margulis, MD, for tissue procurement, Dr. Lev Rappoport, MD, for histological assessment, Mrs. Arnavaz Hakimiyan for the work on the entire project. We also would like to thank Dr.Alessandra Nannini, MD for her help in manuscript editing. The project was supported by research funding from CartiHeal, LLT.
The present ex-vivo study was supported by research funding from CartiHeal, LLT.
Compliance with ethical standards
Conflict of interest
S Chubinskaya, B Di Matteo, L Lovato and F Iacono have nothing to disclose. D Robinson is an employee of CartiHeal LLT (Isreal). E Kon is a paid consultant for CartiHeal LLT (Israel).
Rush University Institutional Review Board granted approval for research with human tissue specimens from deceased donors (Approval number: FWA# 00000482). The present study was conducted under the “Deceased Subjects Rule” and thus did not require the approval of other Ethical committees.
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