About

David Grainger is a faculty member in the Department of Molecular Pharmaceutics at the College of Pharmacy. His email contact is David.Grainger@hsc.utah.edu. The page does not provide specific details about his research focus, background, or key contributions.

Research topics

• Medicine
• Biology
• Computer Science
• Pathology
• Artificial Intelligence
• Anatomy
• Cell biology
• Biomedical engineering
• Chemistry
• Knowledge management
• Surgery
• Immunology
• Cancer research
• Bioinformatics
• Biochemistry
• History

Selected publications

• Detaching Cells From Materials: Techniques and Biomedical Applications

  Advanced Functional Materials · 2026-02-01

  article

  ABSTRACT Having access to high‐quality cell populations is essential for biomedical research, diagnosis, prognosis, and therapeutic applications. Traditional enzymatic methods, such as trypsinization, remain widely used to detach cells from supporting material surfaces, though they often compromise cell surface integrity, viability and functionality. To address these limitations, diverse strategies have emerged that enable a much gentler release of cells from material surfaces. The use of external physical stimuli (like shear stresses, light, temperature, magnetic fields), chemical stimuli (based on changes in pH or ligand‐exchange based detachment) and biological stimuli (like aptamers and nucleic acid sequences) have been explored for the purpose of non‐invasive cell detachment. This review discusses the principles, mechanisms, advantages, and limitations of these most diverse cell detachment technologies. By providing this comprehensive perspective, we hope to guide researchers in selecting the most suitable techniques for their specific needs and to inspire further innovation in this vital biomedical area.

  PublisherDOI

• Juvenile Chondrocyte Cell Sheet Layering Enhances In Vitro Chondrogenic Differentiation

  ACS Biomaterials Science & Engineering · 2026-01-31

  articleOpen access

  Osteoarthritis affects over 30 million US adults and is a leading cause of disability, yet no approved therapies halt or reverse disease progression due to cartilage's limited intrinsic repair capacity. Autologous chondrocyte implantation strategies demonstrate some efficacy but are constrained by high costs, donor variability, and limited scalability. Allogeneic juvenile cartilage-derived chondrocyte (JCC) sheets represent a promising "off-the-shelf" alternative, exhibiting strong proliferative and chondrogenic capacity in both preclinical models and a first-in-human trial. However, restricted per-donor yield and dedifferentiation during ex vivo expansion beyond passage 2 (P2) hinder clinical translation. This study investigated how cell sheet layering and coculture with human bone marrow-derived mesenchymal stromal cells (BMSCs) might restore the chondrogenic capacity of high-passage (P4) JCC sheets, thereby improving the scalability of JCC sheet-based therapies. Layered constructs comprising one-, two-, or three-layer P4 JCC sheets, as well as bilayers of P4 JCC and BMSC sheets in both apical and basal layer orientations, were fabricated and evaluated for in vitro chondrogenesis with and without BMP6 media supplementation. When differentiated with BMP6, all cell sheet constructs produced equally mature hyaline-like cartilage rich in sulfated proteoglycans, collagen II, and aggrecan, although the ultimate thickness varied according to the number of layers. Culture in BMP6-deficient differentiation media revealed cell sheet layering-enhanced chondrogenesis, with triple-layer P4 JCC sheets (J3L) demonstrating hyaline-like cartilage formation equivalent to BMP6 media differentiation. Cocultured JCC-BMSC bilayers showed layer-orientation-dependent outcomes when differentiated without BMP6: JCC-apical (JonB) constructs maintained chondrogenesis comparable to that of JCC-only sheets, while BMSC-apical (BonJ) constructs exhibited impaired chondrogenesis and elevated hypertrophy markers. Cell sheet layering enables high-passage JCC sheets to recover therapeutic potency, facilitating enhanced sheet yields per donor nearly 60-fold and addressing a critical production scalability barrier. These findings support layered allogeneic JCC sheets as a clinically feasible and scalable allogeneic strategy for future cartilage regeneration.

  PublisherOA PDFDOI

• Poor prognosis outcome tumors, bacteria-infected tumors and nanodrugs: current evidence and hypotheses towards a paradigm change for treatment

  Cancer Biology and Medicine · 2026-04-15

  articleOpen access

  New therapies and supportive care have converted several cancer types into chronic conditions. Yet, some tumors exhibit features reproducibly correlated with poor prognosis outcome (PPO-tumors). Bacteria in a tumor environment can inactivate chemotherapeutics and are a feature of PPO-tumors, although standard diagnostic tests for tumor infections do not exist. Optimism is high for nanotechnologic innovations but nanoparticulate chemotherapeutics based on enhanced permeability and retention in a human tumor environment have only shown limited treatment benefits. Moreover, treatment of infected tumors in animals with stimuli-responsive nanocarriers loaded with an antibiotic/chemotherapeutic combination has demonstrated limited benefits compared to treatment with combinations of carrier-free antibiotics and chemotherapeutics. Development of nanoparticulate chemotherapeutics with significant benefits in human clinical use is estimated to take several decades, which is too long for patients with PPO-tumors. Herein we hypothesize the following: 1-all diagnosed PPO-tumors are infected with bacteria; 2-all PPO-tumors in mice and humans exhibit enhanced permeability to chemotherapeutics; and 3-all diagnosed PPO-tumors must be treated from the onset with a combination of carrier-free antibiotics and chemotherapeutics. Each hypothesis was critically evaluated and judged plausible and clinically acceptable. Potential clinical treatment of PPO-tumors, presuming bacterial infection without diagnosis, with an approved antibiotic and chemotherapeutic free drug combination requires a paradigm change in treatment concept towards more lenient antibiotic use. However, many cancer patients already require antibiotics during chemotherapeutic treatment and combined carrier-free antibiotic/chemotherapeutic treatment may provide an immediate pathway to re-sensitize PPO-tumors to clinically used chemotherapeutics and alter the prognosis to a more favourable outcome.

  PublisherOA PDFDOI

• The Enamel Organ Tissue Engineering Singularity of 2040

  The International Journal of Oral & Maxillofacial Implants · 2026-04-01

  article
  PublisherDOI

• Randomised controlled trial comparing antibiotic cement bead pouch versus negative pressure wound therapy for the management of severe open tibia fracture wounds: Beads versus VAC (BvV) protocol

  BMJ Open · 2026-05-01

  articleOpen access

  INTRODUCTION: Early open fracture management aims to minimise the risk of complications. For the most severe open fracture wounds, multiple irrigation and debridement surgeries are required to overcome severe wound contamination, to reassess the evolving tissue injury or to temporise and plan further surgery. When multiple irrigation and debridement surgeries are needed, uncertainty remains about how the open fracture wound should be managed to best minimise complications. The primary aim of this trial is to compare the antibiotic cement bead pouch vs negative pressure wound therapy in the management of patients with severe open tibia fracture wounds. METHODS AND ANALYSIS: BvV is a multicentre, pragmatic, parallel arm randomised controlled trial that aims to enrol 312 adult patients admitted to a participating centre with a severe open tibia fracture requiring multiple irrigation and debridement surgeries. Participants will be randomly allocated on a 1:1 basis to either antibiotic cement bead pouch or negative pressure wound therapy. The primary outcome will be a composite outcome to evaluate clinical status 6 months after randomisation. Using the win ratio approach, we will hierarchically assess the composite outcome in the following order: (i) all-cause mortality, (ii) injury-related amputation of the lower extremity, (iii) unplanned reoperation to manage wound complications, an infection or promote fracture healing and (iv) clinical fracture healing assessed using the Functional IndeX for Trauma (FIX-IT) instrument. ETHICS AND DISSEMINATION: The BvV trial has been approved by a central institutional review board (IRB) (Advarra) for clinical sites in the USA, the ethics board at the coordinating centre at McMaster University (Hamilton Integrated Research Ethics Board), and participating sites not using the central institutional IRB (Fraser Health Research Ethics Board, The University of British Columbia Clinical Research Ethics Board, Newfoundland and Labrador Health Research Ethics Board, University of Manitoba Biomedical Research Ethics Board). Additional clinical sites who are in the start-up phase, as well as any new selected clinical sites, will obtain local approvals prior to initiating trial activities. This will include a clinical site in the UK who is in the process of obtaining the necessary approvals. Recruitment began in November 2023. Both interventions are frequently used to manage severe open fracture wounds, ensuring that the trial results can be easily transitioned into clinical practice. The results of this trial will be disseminated to national and international partners through peer-reviewed publications, academic conferences and stakeholder engagement activities. TRIAL REGISTRATION NUMBER: NCT05615844.

  PublisherOA PDFDOI

• Comparison of human juvenile and adult donor-derived chondrocyte sheets for scalable allogeneic regenerative therapy

  European Cells and Materials · 2025-11-28 · 1 citations

  articleOpen access

  Background: Regeneration of damaged cartilage is challenging, and no reproducible regenerative therapies using mass-producible cell products have been established. This study evaluated the cartilage regeneration capability and therapeutic scalability using cell sheets derived from routinely available surgical waste cartilage tissues of young and adult patients, while also investigating the mechanisms that define the characteristics of each cell type. Methods:We compared the viability, proliferation, and cell sheet characteristics of juvenile cartilage-derived chondrocytes (JCCs) from patients with polydactyly (2.2 ± 1.6 years) and adult cartilage-derived chondrocytes (ACCs) from patients with femoroacetabular impingement (FAI) (34.1 ± 10.6 years)in vitro. Thein vivocartilage regeneration capability of each cell sheet was validated in a nude rat knee cartilage defect model using histological O’Driscoll score evaluation on Safranin-O-stained tissues and immunohistochemistry. JCC sheets (n = 13) and ACC sheets (n = 8) were analyzed using established bulk RNA sequencing pipelines for gene ontology (GO) analysis, gene set enrichment analysis (GSEA), and ingenuity pathway analysis (IPA). Interferon gamma (IFN-γ) was applied to JCC sheet culture for confirmation of the interferon signaling involvement in cell proliferation, cell sheet characteristics, and chondrogenic differentiation.Results:JCC demonstrated higher colony-forming ability and stable high proliferation compared to ACC. Both JCC and ACC sheets formed positively stained hyaline cartilage for Safranin-O, type II collagen, aggrecan, and human vimentin, while being negative for type I collagen, four weeks after rat transplantation. However, the regenerated cartilage from ACC sheet transplantation was found to be thinner compared to that from JCC sheet transplantation. Comprehensive gene analysis revealed significant activation of IFN signaling in the ACC sheets. Furthermore, the addition of exogenous IFN dramatically reduced the proliferation and cartilage formation capability of JCC.Conclusions:JCC sheets exhibit high therapeutic scalability due to their proliferation and cartilage regeneration capabilities presumably derived from sustained low IFN-γ activity. Consideration of the donor age and tissue inflammatory status is essential for the cell source in allogeneic cell therapies. Given their sustainable sourcing from routine surgical discards, JCCs present a commercially viable and scalable option for allogeneic regenerative therapy in cartilage repair.

  PublisherDOI

• Toward Standardized MSC Sheet Fabrication: Role of Initial Seeding Density in Structural and Paracrine Optimization

  Stem Cell Reviews and Reports · 2025-10-24

  article
  PublisherDOI

• The complex and intricate relationship between incremental science, innovation and recognition

  Advanced Drug Delivery Reviews · 2025-10-19

  reviewOpen access

  Science, technology, and innovation are related but distinct, leading to different research incentives. Incremental science, such as refining methods and validating findings, ensures robust results and understanding, laying the groundwork for breakthroughs. Due to pressures for ongoing innovation, fundamental research is frequently seen as an obstacle hindering scientific progress instead of an investment. The time fundamental research requires to bear fruit can detract from its immediate relevance, and impatience surrounding the urgency for rapid innovation further devalues the relatively slow, methodical approach of basic science. But this emphasis can be misleading, as many crucial advances arise from incremental improvements or refinements rather than radical breakthroughs. Insisting on scientific novelty devalues the work that lays the essential groundwork for reliable scientific progress and endorses a culture where only the most sensational achievements are celebrated, marginalising the essential contributions of those engaged in less glamorous, yet equally important, foundational research. We argue that instead of focusing on celebrating novelty and its often-unrealised societal impacts, science and technology should better value more vital basic, incremental, and knowledge-based contributions necessary for sustaining innovation and ensuring its diverse, positive impacts.

  PublisherDOI

• Functional aligned mesenchymal stem cell sheets fabricated using micropatterned thermo-responsive cell culture surfaces

  Materials Today Bio · 2025-03-11 · 14 citations

  articleOpen access

  Mesenchymal stem cells (MSCs) are frequently applied for cell transplantation and regenerative therapy because they secrete diverse therapeutic cytokines that prompt immuno-stimulatory and tissue repair processes. Furthermore, cultured MSC sheets exhibit enhanced cytokine secretion compared to their MSC suspensions, and represent a durable, versatile format for tissue engineering as singular, multi-layered, or multi-cell type sandwiched, transplantable constructs. Tissue engineered implants with various cellular orientations have been reported. In this study, patterned, temperature-responsive culture surfaces were used to prepare oriented MSC sheets. Patterned culture surfaces were fabricated by grafting polyacrylamide (PAAm) onto commercial poly( N -isopropylacrylamide) (PNIPAAm)-modified plastic via photopolymerization using a stripe-patterned photomask. Patterned surfaces were characterized using x-ray photoelectron spectroscopy, fluorescently labeled fibronectin and albumin adsorption assays, wetting (contact angle) measurements, atomic force microscopy, and scanning electron microscopy. Striped grafted patterns of PAAm were fabricated on the PNIPAAm-coated culture substrates, and PAAm polymerized within the PNIPAAm overlayer. Cell-aligned MSC sheets were then produced from MSC culture on this patterned surface, secreting higher amounts of therapeutic cytokines (vascular endothelial growth factor, hepatocyte growth factor, and transforming growth factor-β) than non-aligned MSC control sheets. In addition, aligned MSC sheets maintained enhanced cell multi-potent differentiation capabilities. New, aligned MSC sheets might exhibit improved functional properties for cell sheet transplant therapies. • Stripe patterned culture surfaces were fabricated via photopolymerization. • Patterned culture dish fabricates aligned mesenchymal stem cell sheet. • Aligned mesenchymal stem cell sheet secret higher amounts of therapeutic cytokines. • The stem cell sheet would be applicable for effective cell sheet transplant therapies.

  PublisherDOI

• Navigating human‐nature interactions by exploring plural values across ecosystem states

  People and Nature · 2025-01-19 · 5 citations

  articleOpen access

  Abstract Supporting biodiversity conservation in an effective and sustainable way requires addressing biodiversity loss while satisfying the dependency of people on nature. Critical to this goal is to understand how the benefits and services delivered by ecosystems influence human values, and how these values can be leveraged to promote equitable economic, social and environmental outcomes. However, these values are challenging to capture in complex social‐ecological systems, particularly when the values are not consistent among different groups of stakeholders. We examined the values associated with Box Gum Grassy Woodland agro‐ecological systems in Australia, focusing on two key stakeholder groups that influence management decisions: farmers and ecological specialists. Using a state‐and‐transition model as a boundary object, we identified various dimensions of values—instrumental, intrinsic and relational—across four distinct states of the Box Gum Grassy Woodland: Grassy Woodland, Native Pastures, Crops and Sown/Fertilised Pastures and Revegetated Areas. We found that both groups of stakeholders identified multiple dimensions of values, although the intensity of values (i.e., the total number of values) associated with different states varied significantly—the values of ecological specialist respondents were concentrated in intact Grassy Woodlands, whereas the values of farmer respondents were concentrated in Native Pastures. These results demonstrate that ecological systems influence the values that are generated in human communities, and these values are likely to result in actions that may promote or diminish the presence of certain values. Characterising values and analysing their distribution between ecosystem states for different groups of stakeholders can offer valuable insights into the dynamics of human‐nature interactions and the values that influence human behaviour which can directly transform nature. Read the free Plain Language Summary for this article on the Journal blog.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R43AI043111

  NIH · $100k · 1999

• NIH Grant R01EB001473

  NIH · $2.8M · 2013

• NIH Grant R01GM056751

  NIH · $634k · 2003

• A Novel Self-Renewing Heparin-Binding Anti-microbial Device Surface Coating

  NIH · $236k · 2010–2012

• NSF Young Investigator

  NSF · $281k · 1994–2000

Frequent coauthors

• Barbara Luke

  200 shared

• Judy E. Stern

  Dartmouth Psychiatric Research Center

  161 shared

• Marcelle I. Cedars

  University of California, San Francisco

  154 shared

• N.A. Klein

  150 shared

• William R. Meyer

  132 shared

• John F. Steege

  University of North Carolina at Chapel Hill

  132 shared

• Franklin D. Loffer

  131 shared

• Lisa Peacock

  Louisiana State University Health Sciences Center New Orleans

  130 shared

Labs

• Mei LabPI

Education

• Ph.D., Pharmaceutical Chemistry

  University of Utah

  1987

• B.A.; Engineering modified with Chemistry, Engineering

  Dartmouth College

  1983