Optimizing Bone Graft Performance

In collaboration with UM Orthopaedic Trauma and the Orthopaedic Research Labs, the Alford lab is studying the interplay between bone graft materials and the local wound environment with the goal of leveraging this knowledge to maximize healing of challenging bone injuries. We are using Masquelet's Induced Membrane Technique as a model system. This work is supported by a grant to Dr. Alford from the Musculoskeletal Transplant Foundation.

Gohel N, Senos R, Goldstein SA, Hankenson KD, Hake ME, Alford AI: Evaluation of global gene expression in regenerate tissues during Masquelet treatment. J Orthop Res: 2020. DOI: 10.1002/jor.24676

Alford AI, Nicolaou D, Hake M, McBride-Gagyi S. Masquelet's induced membrane technique: Review of current concepts and future directions. J Orthop Res. 2020 Dec 31. doi: 10.1002/jor.24978

Biological interactions to that could promote successful graft to bone consolidation (Alford et al 2020).

Bone Marrow Microenvironment and Skeletal Growth

In collaboration with UM Pediatric Orthopaedic Surgery and Physical Medicine and Rehabilitation, the Alford lab is studying the interplay between the bone marrow microenvironment and skeletal progenitor cells in adolescents. This work is supported by a grant to Dr. Daniel Whitney (PM&R) from the National Institutes of Health.

Whitney DG, Devlin MJ, Alford AI, Caird MS. Pattern of bone marrow lipid composition measures along the vertebral column: A descriptive study of adolescents with idiopathic scoliosis. Bone. 2021 Jan;142:115702. doi: 10.1016/j.bone.2020.115702

Photomicrograph of the murine growth plate (Andrea Golicz, former UROP student)

Skeletal Extracellular Matrix Biology

Bone is a mineralized composite of type I collagen and a plethora of other ECM proteins, growth factors and cells that dynamically maintain the structural and biological functions of the skeleton. The Alford lab studies an ECM protein called Thrombospondin-2, which regulates angiogenesis, facilitates collagen fibrillogenesis, helps maintain a pool of skeletal progenitor cells and promotes osteoblast differentiation. The Alford lab uses a variety of genetic tools to study TSP2 and its contributions to bone matrix quality and skeletal stem cell physiology.

Alford AI, Stephan C, Kozloff, KM, Hankenson KD. Compound deletion of thrombospondin-1 and -2 results in a skeletal phenotype not predicted by the single gene knockouts. Bone. 2021 Aug 20. doi: 10.1016/j.bone.2021.116156. [Epub ahead of print] PubMed PMID: 34425286

Alford AI, Kozloff KM, Hankenson KD. Extracellular Matrix Networks in Bone Remodeling. Int J Biochem Cell Biol. 2015 Aug;65:20-31

Manley E Jr, Perosky JE, Khoury BM, Reddy AB, Kozloff KM, Alford AI. Thrombospondin-2 deficiency in growing mice alters bone collagen ultrastructure and leads to a brittle bone phenotype. J Appl Physiol (1985). 2015 Oct 15;119(8):872-81.

Transmission Electron Micrographs of Bone Collagen in wild-type (left) and TSP2-deficient (right) mice (Manley et al 2015)