Generation of stem cell-based bioartificial anterior cruciate ligament (ACL) grafts for effective ACL rupture repair

- A bioartificial ACL (baACL) was generated by growing MSCs on biomaterial.
- MSCs were induced to bone at the ends and to ligament in the middle part of the graft.
- Upon implantation, in all modelled pigs a functional ACL-like tissue was constructed.
- The baACL resembled histologically normal ACLs and contained mainly human cells.

In the present study, we combined stem cell technology with a non-absorbable biomaterial for the reconstruction of the ruptured ACL. Towards this purpose, multipotential stromal cells derived either from subcutaneous human adipose tissue (hAT-MSCs) or from induced pluripotent stem cells (iPSCs) generated from human foreskin fibroblasts (hiPSC-MSCs) were cultured on the biomaterial for 21 days in vitro to generate a 3D bioartifical ACL graft. Stem cell differentiation towards bone and ligament at the ends and central part of the biomaterial was selectively induced using either BMP-2/FGF-2 or TGF-β/FGF-2 combinations, respectively. The bioartificial ACL graft was subsequently implanted in a swine ACL rupture model in place of the surgically removed normal ACL. Four months post-implantation, the tissue engineered ACL graft generated an ACL-like tissue exhibiting morphological and biochemical characteristics resembling those of normal ACL.

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