About

Seth Donahue is a professor in the Biomedical Engineering department at the University of Massachusetts Amherst, affiliated with the Riccio College of Engineering. His research focuses on studying the biology, physiology, and mechanics of bone from animals that have adapted to extreme environmental conditions, including Trinidadian guppies, little pocket mice, arctic ground squirrels, bighorn sheep, hibernating bears, and dinosaurs. He also utilizes traditional laboratory rodent models to investigate treatments for osteoporosis and explores tissue engineering approaches to regenerate new bone tissue. Dr. Donahue's work aims to understand bone adaptation and develop regenerative strategies, contributing to advancements in biomedical engineering and orthopaedics.

Research topics

• Composite material
• Materials science
• Engineering
• Computer Science
• Medicine
• Structural engineering
• Acoustics
• Mechanical engineering
• Anatomy
• Physics
• Nanotechnology

Selected publications

• Calvarial Bone Defects Heal Better in Short-Term Ovariectomized Rats Compared to Healthy Rats

  Journal of Musculoskeletal and Neuronal Interactions · 2025-11-30

  articleOpen accessSenior author

  Objectives: Postmenopausal women develop estrogen deficiency which produces a pro-resorptive bone environment, leading to osteoporosis and increased fracture risk.Craniectomies are a common clinical procedure, especially in older populations, where calvarial bone is removed to relieve intracranial pressure (i.e., in the case of traumatic brain injury or stroke).Cranial reconstruction surgeries often result in failure due to infection or resorption of autograft material.Despite the need for calvarial bone graft alternatives for older patients, there is limited literature available on the effects of estrogen deficiency on skull bone metabolism and healing.Methods: The purpose of this work was to assess the effects of short-term ovariectomy (OVX) on calvarial bone properties and on the healing of 3.5 mm unilateral calvarial defects.Results: Surprisingly, the intact calvarial bone of OVX rats had higher bone volume, thickness, and number of remodeling cavities than intact calvaria of sham rats.Normalized measures of bone volume showed consistently more calvarial defect healing in OVX compared to sham rats at 4-, 8-, and 12-weeks post-surgery.Conclusion: These findings have implications for future investigations on therapies for treating calvarial bone defects in ovariectomy-induced osteoporotic rats.

  PublisherOA PDFDOI

• Multiphoton imaging for quantification of mesenchymal stem cell survival and distribution in PEG granular hydrogel scaffolds post-implantation into rat cranial bone defects

  Biomedical Engineering Advances · 2024-11-01

  articleOpen accessSenior author

  Mesenchymal stem cells (MSCs) are promising candidates for cellular therapies aimed at promoting bone regeneration due to their secretory properties and osteoblastic differentiation capacity. However, typically < 5% of delivered MSCs are retained at the healing site within days of delivery via injection. In this work, granular PEG hydrogel scaffolds were used to deliver MSCs, labeled with fluorescent Quantum Dots, into critical-sized rat calvarial bone defects. The presence, survival, and distribution of MSCs within the hydrogel scaffold were evaluated with multiphoton microscopy at 3- and 7-days post-implantation. Additionally, endogenous cell infiltration into scaffolds was quantified, and markers for M1 and M2 macrophages were identified with immunohistochemistry. This multiphoton microscopy technique provides a quantitative analysis of exogenous MSC presence and survival and allows for micron-level spatial resolution of cell distribution throughout the implanted scaffolds. When ~750,000 MSCs were implanted in a calvarial bone defect via PEG granular hydrogel scaffolds, ~27% and ~8% survived 3- and 7-days post-implantation, respectively. At 3- and 7-days post-implantation, exogenous MSCs and infiltrating endogenous cells, including M1 and M2 macrophages, were well distributed throughout the scaffolds. This multiphoton microscopy technique could be used to assess biomaterial delivery systems that can improve exogenous MSC presence and survival, facilitate endogenous cell infiltration, and investigate exogenous-endogenous cell interactions for bone regeneration therapies.

  PublisherDOI

• Multiphoton Imaging for Quantification of Mesenchymal Stem Cell Survival and Distribution in Peg Granular Hydrogel Scaffolds Post-Implantation into Rat Cranial Bone Defects

  SSRN Electronic Journal · 2024-01-01

  preprintOpen accessSenior author
  PublisherDOI

• The Horn-Horncore Interface Morphology of Bighorn Sheep Increases Contact Surface to Enhance Strength and Facilitate Load Transfer from the Horn to the Energy Absorbing Horncore During Ramming

  SSRN Electronic Journal · 2023-01-01

  preprintOpen accessSenior author
  PublisherDOI

• The Osteogenic and Angiogenic Potential of Microrna-26a, Delivered Via the Non-Viral Peptide Rala, for Bone Repair

  SSRN Electronic Journal · 2023-01-01

  preprintOpen access
  PublisherDOI

• The morphology of the interfacial tissue between bighorn sheep horn and bony horncore increases contact surface to enhance strength and facilitate load transfer from the horn to the horncore

  Acta Biomaterialia · 2023-12-09 · 5 citations

  articleSenior author
  PublisherDOI

• How the geometry and mechanics of bighorn sheep horns mitigate the effects of impact and reduce the head injury criterion

  Bioinspiration & Biomimetics · 2023-01-18 · 10 citations

  articleOpen accessSenior author

  Abstract Male bighorn sheep ( Ovis canadensis ) participate in seasonal ramming bouts that can last for hours, yet they do not appear to suffer significant brain injury. Previous work has shown that the keratin-rich horn and boney horncore may play an important role in mitigating brain injury by reducing brain cavity accelerations through energy dissipating elastic mechanisms. However, the extent to which specific horn shapes (such as the tapered spiral of bighorn sheep) may reduce accelerations post-impact remains unclear. Thus, the goals of this work were to (a) quantify bighorn sheep horn shape, particularly the cross-sectional areal properties related to bending that largely dictate post-impact deformations, and (b) investigate the effects of different tapered horn shapes on reducing post-impact accelerations in an impact model with finite element analysis. Cross-sectional areal properties indicate bighorn sheep horns have a medial–lateral bending preference at the horn tip ( p = 0.006), which is likely to dissipate energy through medial–lateral horn tip oscillations after impact. Finite element modeling showed bighorn sheep native horn geometry reduced the head injury criterion (HIC 15 ) by 48% compared to horns with cross-sections rotated by 90° to have a cranial–caudal bending preference, and by 125% compared to a circular tapered spiral model. These results suggest that the tapered spiral horn shape of bighorn sheep is advantageous for dissipating energy through elastic mechanisms following an impact. These findings can be used to broadly inform the design of improved safety equipment and impact systems.

  PublisherOA PDFDOI

• The osteogenic and angiogenic potential of microRNA-26a delivered via a non-viral delivery peptide for bone repair

  Journal of Controlled Release · 2023-09-09 · 14 citations

  article
  PublisherDOI

• Development of miR-26a-activated scaffold to promote healing of critical-sized bone defects through angiogenic and osteogenic mechanisms

  Biomaterials · 2023-11-13 · 34 citations

  articleOpen access

  Very large bone defects significantly diminish the vascular, blood, and nutrient supply to the injured site, reducing the bone's ability to self-regenerate and complicating treatment. Delivering nanomedicines from biomaterial scaffolds that induce host cells to produce bone-healing proteins is emerging as an appealing solution for treating these challenging defects. In this context, microRNA-26a mimics (miR-26a) are particularly interesting as they target the two most relevant processes in bone regeneration-angiogenesis and osteogenesis. However, the main limitation of microRNAs is their poor stability and issues with cytosolic delivery. Thus, utilising a collagen-nanohydroxyapatite (coll-nHA) scaffold in combination with cell-penetrating peptide (RALA) nanoparticles, we aimed to develop an effective system to deliver miR-26a nanoparticles to regenerate bone defects in vivo. The microRNA-26a complexed RALA nanoparticles, which showed the highest transfection efficiency, were incorporated into collagen-nanohydroxyapatite scaffolds and in vitro assessment demonstrated the miR-26a-activated scaffolds effectively transfected human mesenchymal stem cells (hMSCs) resulting in enhanced production of vascular endothelial growth factor, increased alkaline phosphatase activity, and greater mineralisation. After implantation in critical-sized rat calvarial defects, micro CT and histomorphological analysis revealed that the miR-26a-activated scaffolds improved bone repair in vivo, producing new bone of superior quality, which was highly mineralised and vascularised compared to a miR-free scaffold. This innovative combination of osteogenic collagen-nanohydroxyapatite scaffolds with multifunctional microRNA-26a complexed nanoparticles provides an effective carrier delivering nanoparticles locally with high efficacy and minimal off-target effects and demonstrates the potential of targeting osteogenic-angiogenic coupling using scaffold-based nanomedicine delivery as a new "off-the-shelf" product capable of healing complex bone injuries.

  PublisherOA PDFDOI

• Bone adaptation and osteoporosis prevention in hibernating mammals

  Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · 2023-03-03 · 5 citations

  article1st authorCorresponding
  PublisherDOI

Recent grants

• NIH Grant R41DK078407

  NIH · $238k · 2010

• NIH Grant R42DK078407

  NIH · $1.1M · 2013

• Endocannabinoid Regulation of Bone Metabolism in Hibernating Marmots

  NSF · $118k · 2018–2020

• Endocannabinoid Regulation of Bone Metabolism in Hibernating Marmots

  NSF · $455k · 2016–2018

• NIH Grant R15AR050420

  NIH · $589k · 2012

Frequent coauthors

• Meghan E. McGee‐Lawrence

  Augusta University

  24 shared

• Samantha J. Wojda

  23 shared

• Michael R. Vaughan

  Virginia Tech

  18 shared

• Neil A. Sharkey

  Pennsylvania State University

  16 shared

• Nicholas Dunne

  Trinity College Dublin

  11 shared

• Hal L. Black

  Brigham Young University

  10 shared

• Henry J. Donahue

  Virginia Commonwealth University

  10 shared

• Luca H. Fuller

  University of Massachusetts Boston

  10 shared