Alayna E. Loiselle, Ph.D.
Post-doctoral training 2009-2013,
Penn State College of Medicine
Ph.D. 2009, University of Rochester
School of Medicine and Dentistry
Assistant Professor of Orthopaedics
Primary Appointment: Department of Orthopaedics
Center Affiliation: Center for Musculoskeletal Research
Graduate Program Affiliations: Pathways of Human Disease and Genetics, Development, and Stem Cells
The overarching goal of our research program is to identify novel strategies to improve flexor tendon healing by reducing the formation of range of motion (ROM) limiting adhesions, without compromising mechanical strength. Flexor tendons glide through a synovial sheath to facilitate digit ROM and movement of the hand. Following injury, up to 40% of primary flexor tendon repairs will heal with unsatisfactory outcomes. The primary complication involves a robust scar tissue response, which forms adhesions between the tendon and synovial sheath, resulting impaired gliding function.
We have developed a novel murine model of intrasynovial FT healing, which mimics many aspects of healing in humans including abundant adhesion formation, impaired ROM and early decrements in tendon strength. We continue to use this model to gain a greater understanding of the cell and molecular processes involved in scar and adhesion formation in order to identify therapeutic targets to improve FT healing as outlined in the projects below.
Type II diabetes mellitus (T2DM) dramatically affects the baseline function of flexor tendons; up to 50% of diabetic patients experience impaired hand function, including increased rates of tenosynovitis, and carpal tunnel syndrome. In addition to decrements in tendon gliding function, deficits in mechanical properties are also observed, rendering diabetic tendons more susceptible to rupture. Considering that the complication rate of primary flexor tendon repairs is as high as 40% in non-diabetic patients, and that T2DM further impairs tendon healing, it is imperative to understand the cellular and molecular components of diabetic tendinopathy. Our murine model of diet induced obesity (using a high fat diet [HFD]) recapitulates several aspects of the ‘diabetic hand syndrome’ observed clinically in diabetic patients and will be a powerful tool to understand the cellular and molecular changes associated with diabetic tendinopathy and impaired healing.
Pharmacological modification of scar formation during healing
We have previously demonstrated that Mmp9-/- mice have accelerated resolution of adhesion formation and that expression of Mmp9 in bone marrow derived cells is a driving force behind scar and adhesion formation during flexor tendon healing. In vitro studies have demonstrated that Mmp9 expression is induced in bone marrow stromal cells by the inflammatory mediator PGE2 specifically through the EP4 receptor. In parallel projects we will study the effects of systemic pharmacological inhibition of either Mmp9 or EP4 on flexor tendon repair with the overall hypothesis that inhibition of the late inflammatory phase and suppression of collagen catabolism will attenuate the scar/ adhesion formation response and enhance healing.
Elucidating the cell populations involved in repair and scar formation
We have previously demonstrated that bone marrow derived cells migrate specifically to the flexor tendon repair site after injury, however, the precise roles that these cells play, and the contribution of different subpopulations remain unclear. We have also identified activation of a specific tendon resident cell population as a potential precursor of scar formation. Using lineage-tracing studies to follow specific cell populations we will identify the cells involved in each aspect of the repair process and delineate the contribution of these cells to both normal healing and the pathologic formation of scar tissue.
Tendon Biology & Healing:
- Loiselle, AE; GA Bragdon, JA Jacobson, S Hasslund, Z Cortes, DJ Mitten, EM Schwarz, HA Awad, RJ O’Keefe. 2009. Remodeling of Murine Intrasynovial Tendon Adhesions Following Injury: Mmp and Neotendon Gene Expression. Journal of Orthopaedic Research. 27: 833-840.
- Loiselle, AE; BJ Frisch, MJ Wolenski, JA Jacobson, LM Calvi, EM Schwarz, HA Awad, RJ O’Keefe. 2012. Bone Marrow Derived Matrix Metalloproteinase-9 is Associated with Fibrous Adhesion Formation after Murine Flexor Tendon Injury. PlosOne. 7(7):e40602. PMCID: PMC3394706
- MB Geary, CA Orner, F Bawany, HA Awad, WC Hammert, RJ O’Keefe, AE Loiselle. 2015. Effects of Systemic EP4 Inhibition on Adhesion Formation and Matrix Deposition in a Murine Model of Flexor Tendon Repair. PlosOne. 10(8):e0136351. PMCID: PMC4552471
- CA Orner, MB Geary, WC Hammert, RJ O’Keefe, AE Loiselle. 2016. Low-Dose and Short-Duration Matrix Metalloproteinase 9 Inhibition Does Not Affect Adhesion Formation during Murine Flexor Tendon Healing. Plast Reconstr Surg. Mar;137(3) :545e-553e. PMCID: PMC4770830
- JE Ackerman, AE Loiselle. 2016. Murine Flexor Tendon Injury and Repair Surgery. J Vis Exp. 2016 Sep 19; (115).
- Ackerman JE, Bah I, Jonason JH, Buckley MR, Loiselle AE. 2017. Aging Does Not Alter Tendon Mechanical Properties During Homeostasis, but does Impair Flexor Tendon Healing. J Orthop Res. 2017 Apr 17. doi:10.1002/jor.23580. [Epub ahead of print]
Bone Biology & Regeneration:
- Loiselle, AE; EM Paul, GS Lewis, HJ Donahue. 2012. Osteoblast and Osteocyte-Specific Loss of Connexin43 Results in Delayed Bone Formation and Healing During Murine Fracture Healing. Journal of Orthopaedic Research. 31(1): 147-54. PMCID: PMC3640531
- Loiselle AE; SA Lloyd, EM Paul, GS Lewis, HJ Donahue. 2013. Inhibition of GSK-3β Rescues the Impairments in Bone Formation and Mechanical Properties Associated with Fracture Healing in Osteoblast Selective Connexin 43 Deficient Mice. PlosOne. 8(11): e81399. PMCID: PMC3832658
- Loiselle, AE; L Wei, M Faryad, J Gao, A Lakhtakia, HJ Donahue. 2013. Specific Biomimetic Hydroxyapatite Nanotopographies with Fractal Distributions Enhance Osteoblastic Differentiation and Bone Graft Osteointegration. Tissue Eng. 19 (15-16): 1704-12. PMCID: PMC3700012
- Xie, CX; BJ Li, M Xue, A Naik, A Lin, A Loiselle, EM Schwarz, R Guldberg, RJ O’Keefe, X Zhang. 2009. Rescue of Impaired Fracture Healing in COX-2-/- mice by Activation of Prostaglandin E2 Receptor Subtype 4. American Journal of Pathology. 175(2): 772-85. PMCID: PMC2716972
- Lloyd, SA; AE Loiselle, Y Zhang, HJ Donahue. 2013. Connexin 43 Deficiency Desensitizes Bone to the Effects of Mechanical Unloading through Modulation of Both Arms of Bone Remodeling. Bone. 57(1):76-83.
- Govey, PM; JM Jacobs, KM Waters, AE Loiselle, NJ Karin, HJ Donahue. 2014. Integrative Transcriptomic and Proteomic Analysis of Osteocytic Cells Exposed to Fluid Flow Reveals Novel Mechano-sensitive Signaling Pathways. J Biomechanics. 47(8):1838-45. PMCID: PMC4037855
- Lim, JY#; AE Loiselle#, JS Lee, HJ Donahue. 2011. Optimizing the Osteogenic Potential of Adult Stem Cells Skeletal Regeneration. Journal of Orthopaedic Research. 29(11): 1627-33. #Co-authorship. PMCID: PMC3263698
- Loiselle, AE; JX Jiang, HJ Donahue. 2012. Gap Junction and Hemichannel Functions in Osteocytes. Bone. 54(2): 205-12.
- Lloyd, SA#; AE Loiselle#, Y Zhang, HJ Donahue. 2014. Shifting Paradigms on the Role of Connexin43 in the Skeletal Response to Mechanical Signals. Journal of Bone and Mineral Research. 29(2): 275-86. #Co-authorship.
- AE Loiselle, M Kelly, WC Hammert. 2015. Biological augmentation of flexor tendon repair: A challenging cellular Landscape. J Hand Surgery. 41(1):144-9. PMID: 26652792.
A complete and current list of publications can be found here: