Sarah Emily DiIorio

All Publications

• Understanding Tendon Fibroblast Biology and Heterogeneity. Biomedicines DiIorio, S. E., Young, B., Parker, J. B., Griffin, M. F., Longaker, M. T. 2024; 12 (4)

  Abstract

  Tendon regeneration has emerged as an area of interest due to the challenging healing process of avascular tendon tissue. During tendon healing after injury, the formation of a fibrous scar can limit tendon strength and lead to subsequent complications. The specific biological mechanisms that cause fibrosis across different cellular subtypes within the tendon and across different tendons in the body continue to remain unknown. Herein, we review the current understanding of tendon healing, fibrosis mechanisms, and future directions for treatments. We summarize recent research on the role of fibroblasts throughout tendon healing and describe the functional and cellular heterogeneity of fibroblasts and tendons. The review notes gaps in tendon fibrosis research, with a focus on characterizing distinct fibroblast subpopulations in the tendon. We highlight new techniques in the field that can be used to enhance our understanding of complex tendon pathologies such as fibrosis. Finally, we explore bioengineering tools for tendon regeneration and discuss future areas for innovation. Exploring the heterogeneity of tendon fibroblasts on the cellular level can inform therapeutic strategies for addressing tendon fibrosis and ultimately reduce its clinical burden.

  View details for DOI 10.3390/biomedicines12040859

  View details for PubMedID 38672213

  View details for PubMedCentralID PMC11048404

• Analysis of Collagen Extracellular Matrix Ultrastructure in Mouse Long Bone Distraction Osteogenesis Diiorio, S., Guo, J. L., Griffin, M., Huber, J. L., Downer, M., Berry, C., Wan, D. C., Longaker, M. T. LIPPINCOTT WILLIAMS & WILKINS. 2023: S378-S379

  View details for Web of Science ID 001094086301225

• Tissue Microenvironment a Key Driver in Fibrotic Capsules Formed During Foreign Body Response Parker, J. B., Griffin, M., Downer, M., Morgan, A., Guo, J. L., Liang, N., Berry, C., Diiorio, S., Wan, D. C., Longaker, M. T. LIPPINCOTT WILLIAMS & WILKINS. 2023: S393

  View details for Web of Science ID 001094086301255

• Understanding Fibroblast Heterogeneity in Form and Function. Biomedicines Parker, J. B., Valencia, C., Akras, D., DiIorio, S. E., Griffin, M. F., Longaker, M. T., Wan, D. C. 2023; 11 (8)

  Abstract

  Historically believed to be a homogeneous cell type that is often overlooked, fibroblasts are more and more understood to be heterogeneous in nature. Though the mechanisms behind how fibroblasts participate in homeostasis and pathology are just beginning to be understood, these cells are believed to be highly dynamic and play key roles in fibrosis and remodeling. Focusing primarily on fibroblasts within the skin and during wound healing, we describe the field's current understanding of fibroblast heterogeneity in form and function. From differences due to embryonic origins to anatomical variations, we explore the diverse contributions that fibroblasts have in fibrosis and plasticity. Following this, we describe molecular techniques used in the field to provide deeper insights into subpopulations of fibroblasts and their varied roles in complex processes such as wound healing. Limitations to current work are also discussed, with a focus on future directions that investigators are recommended to take in order to gain a deeper understanding of fibroblast biology and to develop potential targets for translational applications in a clinical setting.

  View details for DOI 10.3390/biomedicines11082264

  View details for PubMedID 37626760

• Developing a Mouse Model to Evaluate Tibial Distraction Osteogenesis DiIorio, S., Tevlin, R., Shah, H. N., Salhotra, A., Griffin, M., Januszyk, M., Wan, D. C., Longaker, M. T. LIPPINCOTT WILLIAMS & WILKINS. 2023: S90

  View details for Web of Science ID 000989943300230

• Musculoskeletal tissue engineering: Adipose derived stromal cell implementation for the treatment of osteoarthritis. Biomaterials Tevlin, R., desJardins-Park, H., Huber, J., DiIorio, S. E., Longaker, M. T., Wan, D. C. 2022; 286: 121544

  Abstract

  Osteoarthritis (OA) is a progressive degenerative joint disease which results in chronic degeneration of articular cartilage and sclerosis of bone. While tendons and ligaments may heal to a limited extent, articular cartilage has poor intrinsic regenerative potential, and critical-sized bone defects and pathological fractures cannot regenerate spontaneously. OA represents a significant burden of disease globally, affecting 240 million people in the world. The objective of tissue engineering is to recapitulate the natural healing cascade and developmental process by transplanting stromal and progenitor cells which can act directly or indirectly. As the ultimate goal of regenerative medicine is to avoid in vitro expansion of cells and its associated complications, the adipose-derived stromal cell (ASC) is an attractive progenitor cell for tissue engineering for treatment of OA. While clinical studies are still in their infancy, ASCs together with novel scaffold materials represent promising treatment options for patients suffering from OA. How ASCs exert their regenerative potential is a topic of debate, whereby it may be a result of direct differentiation of ASCs into the desired regenerating tissue, and/or through paracrine activity. With the advancement of material science, it is increasingly possible to enhance engraftment of ASCs through the use of biomaterials or to direct progenitor cell fate by activating biophysical signals through designed material microstructures. There are currently over 180 completed or ongoing registered early stage clinical trials involving ASCs, with 17 completed studies reviewed herein detailing the use of ASCs in OA. In order for ASC therapy to become an "off-the-shelf" option for treating OA, several strategies are currently being explored such as ASC cryopreservation and use of allogeneic ASCs. Newer approaches, such as exosome therapy, allow for the use of acellular ASC-derived therapies and are also currently the focus of ongoing investigations.

  View details for DOI 10.1016/j.biomaterials.2022.121544

  View details for PubMedID 35633592

• DENT-seq for genome-wide strand-specific identification of DNA single-strand break sites with single-nucleotide resolution GENOME RESEARCH Elacqua, J. J., Ranu, N., DiIorio, S. E., Blainey, P. C. 2021; 31 (1): 75–87

  Abstract

  DNA single-strand breaks (SSBs), or "nicks," are the most common form of DNA damage. Oxidative stress, endogenous enzyme activities, and other processes cause tens of thousands of nicks per cell per day. Accumulation of nicks, caused by high rates of occurrence or defects in repair enzymes, has been implicated in multiple diseases. However, improved methods for nick analysis are needed to characterize the mechanisms of these processes and learn how the location and number of nicks affect cells, disease progression, and health outcomes. In addition to natural processes, including DNA repair, leading genome editing technologies rely on nuclease activity, including nick generation, at specific target sites. There is currently a pressing need for methods to study off-target nicking activity genome-wide to evaluate the side effects of emerging genome editing tools on cells and organisms. Here, we developed a new method, DENT-seq, for efficient strand-specific profiling of nicks in complex DNA samples with single-nucleotide resolution and low false-positive rates. DENT-seq produces a single deep sequence data set enriched for reads near nick sites and establishes a readily detectable mutational signal that allows for determination of the nick site and strand with single-base resolution at penetrance as low as one strand per thousand. We apply DENT-seq to profile the off-target activity of the Nb.BsmI nicking endonuclease and an engineered spCas9 nickase. DENT-seq will be useful in exploring the activity of engineered nucleases in genome editing and other biotechnological applications as well as spontaneous and therapeutic-associated strand breaks.

  View details for DOI 10.1101/gr.265223.120

  View details for Web of Science ID 000607253900007

  View details for PubMedID 33355294