Engineered Phalangeal Grafts for Children with Symbrachydactyly: A Proof of Concept

Overview

Journal J Tissue Eng

Date 2024 Jun 14

PMID 38872920

Authors

Romain Schaller

Adrien Moya

Gangyu Zhang

Mansoor Chaaban

Robert Paillaud

Ewelina M Bartoszek

Dirk J Schaefer

Ivan Martin

Alexandre Kaempfen

Arnaud Scherberich

Affiliations

Soon will be listed here.

Abstract

Tissue engineering approaches hold great promise in the field of regenerative medicine, especially in the context of pediatric applications, where ideal grafts need to restore the function of the targeted tissue and consider growth. In the present study, we aimed to develop a protocol to engineer autologous phalangeal grafts of relevant size for children suffering from symbrachydactyly. This condition results in hands with short fingers and missing bones. A previously-described, developmentally-inspired strategy based on endochondral ossification (ECO)-the main pathway leading to bone and bone marrow development-and adipose derived-stromal cells (ASCs) as the source of chondroprogenitor was used. First, we demonstrated that pediatric ASCs associated with collagen sponges can generate hypertrophic cartilage tissues (HCTs) that remodel into bone tissue via ECO. Second, we developed and optimized an protocol to generate HCTs in the shape of small phalangeal bones (108-390 mm) using freshly isolated adult cells from the stromal vascular fraction (SVF) of adipose tissue, associated with two commercially available large collagen scaffolds (Zimmer Plug and Optimaix 3D). We showed that after 12 weeks of implantation in an immunocompromised mouse model such upscaled grafts remodeled into bone organs (including bone marrow tissues) retaining the defined shape and size. Finally, we replicated similar outcome (albeit with a slight reduction in cartilage and bone formation) by using minimally expanded pediatric ASCs (3 × 10 cells per grafts) in the same and settings, thereby validating the compatibility of our pediatric phalanx engineering strategy with a clinically relevant scenario. Taken together, these results represent a proof of concept of an autologous approach to generate osteogenic phalangeal grafts of pertinent clinical size, using ASCs in children born with symbrachydactyly, despite a limited amount of tissue available from pediatric patients.

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