About

Matthew B. Wheeler is a Professor in the Department of Bioengineering at the University of Illinois Urbana-Champaign. His primary research area is Molecular, Cellular, and Tissue Engineering, with a focus on regenerative tissue engineering. His work involves the development and validation of embryonic stem cells, transgenic animals, and genetic modification techniques in various species including pigs and cattle. Wheeler has contributed extensively to the understanding of cellular and molecular mechanisms underlying tissue regeneration and has advanced the application of transgenic technology in biomedicine and agriculture. His research also encompasses the manipulation of embryonic genomes and the development of microfluidic techniques for assisted reproduction, reflecting a broad engagement with innovative biotechnological methods.

Research topics

• Medicine
• Biology
• Chemistry
• Computer Science
• Immunology
• Biochemistry
• Emergency medicine
• Biomedical engineering
• Bioinformatics
• Chromatography
• Medical emergency
• Cell biology
• Microbiology
• Virology
• Anesthesia
• Simulation

Selected publications

• Effect of follicle ablation before ovum pick-up in Girolando cattle

  Journal of Scientific Agriculture · 2025-08-28

  articleOpen accessSenior author

  The present study characterized the effect of follicle ablation (FA) intervals on the follicular population and the quantity and quality of cumulus-oocyte complexes (COCs) from 1/2 and 1/4 Girolando donors (n=125 and n=110, respectively) at Ovum Pick-Up (OPU). The timing for that FA has not been definitively established. Our hypothesis was that FA in 1/2 and 1/4 blood Girolando donors performed 48 hours prior to OPU provided more and higher quality COCs than at 72 hours post-FA. To test this hypothesis, FA performed 48 h or 72 h before OPU, and the ovarian follicular population (grouped by size) and quality (grade I-IV) of COCs recovered from OPU were evaluated. The FA 48 h and 72 h groups had a greater estimated number of medium-sized follicles (more developed) compared with the control group without FA (18.39±1.42, 14.98±1.42, and 10.84±1.42 follicles, respectively, P<0.01) at OPU. Furthermore, there was a greater number of highest-quality COCs at FA 48 h than at FA 72 h and control (2.09±0.31, P= 0.004, 1.11±0.31, and 0.92±0.31 COCs, respectively). In comparison, 1/2 Girolando had greater counts of medium (18.3±2.02, P=0.05) and total follicles (33.34±2.67, P=0.02) and grade IV COC (5.52±0.64, P<0.01) than 1/4 Girolando (11.35±2.02, 22.56±2.67, 0.77±0.64, respectively). The association of FA with OPU on 1/2 and 1/4 Girolando has advantageous effects, resulting in the aspiration of more developed follicles and better-quality oocytes. Besides that, 1/2 Girolando has a greater follicular count than 1/4 Girolando, although these crosses respond similarly to FA. Overall, FA improves OPU outcomes.

  PublisherOA PDFDOI

• 3D‐Printed Gastrointestinal Stents: In Vivo Evaluation in a Swine Small Bowel Perforation Model

  Advanced Healthcare Materials · 2025-12-26

  articleOpen accessSenior authorCorresponding

  Gastrointestinal fistulae and perforations can lead to severe complications including sepsis and patient death. Implantation of personalized gastrointestinal stents can prevent leakage and ameliorate complications, without requiring removal post-healing. In this work, the efficacy of 3D-printed gastrointestinal stents composed of poly-lactic-acid (PLA) is evaluated in an in vivo swine model. Custom stent dimensions are determined for each subject using computed tomography imaging, and stents are implanted after an intestinal incision is made. A 1-cm intestinal defect is maintained over the stent surface to evaluate the ability of the stents to retain intestinal contents over a span of two weeks. Stent efficacy is evaluated after necropsy by histology and scanning electron microscopic analysis. Stents were found to prevent abdominal sepsis over the two-week period, even in the presence of an intestinal defect.

  PublisherOA PDFDOI

• Development of a Porcine Model for the Testing of the RapidVent Emergency Ventilator for the Treatment of COVID-19

  2025-07-23

  articleOpen access1st authorCorresponding

  Background: The COVID-19 pandemic brought forward the need for rapidly producible and affordable ventilators due to widespread incidence of respiratory distress, which led to a desperate need for mechanical ventilators. To meet this need, a team was assembled to design a gas-powered emergency ventilator, named RapidVent. The interdisciplinary team designing RapidVent based the design of commercially available ventilators and used additive manufacturing to rapidly produce a prototype that was tested for over two million cycles. Once the prototype was designed and its functions were confirmed, it was ready to be tested in animals. Methods and Findings: The pig (Sus scrofa) is well-studied for biomedical instrument testing, but ventilator testing using a live, healthy animal has not been explored. Three tests were performed to determine if RapidVent would work with a live subject and to see if adding weight to the ribs of a laterally recumbent animal could simulate labored breathing. The first was a pilot study to determine if the prototype would function while connected to a patient that is breathing on their own. The second test was used to determine if the device could withstand continuous extended use. The third test was to determine if the control parameters of the RapidVent prototype could be adjusted to control the physiological parameters of the pig. Conclusion: The RapidVent Emergency Ventilator withstands continuous use over an extended period and allows for the control of physiological parameters of the pig. Weight added to the ribs of the animal may be a viable model for labored breathing with more evidence.

  PublisherDOI

• 86 Randel Lecture: Bovine Embryo Evaluation—From Optics to Omics: My Journey

  Journal of Animal Science · 2025-06-01

  articleOpen access1st authorCorresponding

  Abstract Evaluating bovine embryos for transfer and successful pregnancy has been challenging since the inception of embryo transfer in cattle over six decades ago. Despite thousands of publications on bovine embryo evaluation, no consensus or gold standard for assessing their developmental potential in vivo exists. This challenge extends beyond embryos to gametes. Various microscopic techniques [e.g., differential interference contrast, electron, fluorescent, time-lapse, and artificial intelligence (AI)-based microscopy and non-microscopic methodologies (including genomics, transcriptomics, epigenomics, proteomics, metabolomics, and nuclear magnetic resonance)] have been explored to supplant and surpass morphological evaluation. Many research tools that accurately determine embryo quality and viability are invasive, costly, labor-intensive, and time-consuming, making them impractical for field use. Future research should focus on creating field-friendly, simple benchtop tests based on existing findings, particularly from omics-based methodologies. Time-lapse monitoring and AI-based automated image analysis could provide accurate embryo evaluations. Further research is needed to develop economically viable options for field applications. Recent work has explored potential uses of nuclear magnetic resonance (NMR) imaging, label-free microscopy, especially holographic techniques like gradient light interference microscopy (GLIM), spatial light interference microscopy (SLIM) and multiphoton holographic microscopy in in vitro fertilization (IVF) labs. The ideal embryo evaluation tool should be accurate, objective, non-invasive, affordable, and simple for widespread adoption by facilities worldwide. It’s unlikely that transcriptomics, proteomics, or metabolomics can be directly used for field evaluations. However, biomarkers identified through these methods could guide the development of simple, affordable benchtop techniques for in-field use. Further research into advanced microscopy and AI-based automated image processing may lead to affordable, widely adoptable methods. The next generation of microscopy, capable of providing objective markers for gamete and embryo quality, is on the horizon. My journey in embryo biology, and especially embryo evaluation, has not been linear. I started college, studying wildlife and fisheries biology. As an undergraduate, I was fortunate to meet Professor Gary B. Anderson at the University of California-Davis in the early 1970s. He was exploring this new field of embryo transfer in cattle. This meeting profoundly changed my life and career trajectory. I completed my MS degree studying twinning in beef cattle using embryo transfer. I went from California to study for a doctorate in physiology and biophysics exploring bovine IVF at Colorado State University under Professor George E. Seidel, Jr. These two great scientists, mentors, and dear friends provided the foundation for my career of over 40 years studying embryo biology in not only cattle but mice, rats, rabbits, swine, horses, sheep, goats, frogs, white-tailed deer and various other species. Great mentors have a profound and lasting impact on their students. I am an example of having had great support and collaborations with many mentors throughout my career.

  PublisherOA PDFDOI

• Label-free super-multiplex multiphoton imaging microscopy (Conference Presentation)

  2025-03-20

  article

  Multiphoton fluorescence microscopy is a powerful tool for revealing complex biological systems with high contrast, minimal out-of-focus bleaching, and deep penetration. However, clinical application faces challenges like the need for stable, tunable laser sources, comprehensive biological information, phototoxicity, and developing universal quality control tools. We developed a new generation label-free super-multiplex multiphoton imaging microscopy, enabling co-registered label-free 4-photon (tryptophan), 3-photon (NAD(P)H), 2-photon (FAD, porphyrin/lipofuscin), second harmonic (collagen), third harmonic (optical heterogeneity), and fluorescence lifetime imaging with single-shot, single-band excitation near 1110 nm. Our laser source features tunable wavelength (950-1150 nm), pulse repetition rate (1-10 MHz), and pulse width (40-400 fs), with stability over 2000 hours. We revealed phototoxicity mechanisms in nonlinear imaging, identified safe imaging parameters, and developed a universal tool for objective imaging performance comparison. This system maximizes fluorescence microscopy information while minimizing harm, paving the way for clinical translation.

  PublisherDOI

• Assisted reproductive technologies and genetic improvement strategies for enhancing livestock production and food security in Tropical East Africa: A review

  Journal of Scientific Agriculture · 2025-09-15 · 1 citations

  articleOpen accessSenior author

  Despite an increase in global food availability, food insecurity remains a pressing global challenge affecting millions across developed and developing nations. This issue is particularly severe in developing countries in tropical regions, where harsh climatic conditions, low agricultural productivity, and limited access to resources intensify the challenge of food insecurity. Africa exemplifies these challenges, with approximately 20% of the total population undernourished. East Africa is no stranger to these statistics with 31.8% of the country’s children under 5 years old being malnourished. Many livestock production systems in tropical East Africa operate significantly below their potential due to constraints including climate vulnerability, endemic diseases, and low genetic production capacity of indigenous breeds. Improving livestock productivity has been an area of focus for improving food security for many years. Applying our knowledge of environmental adaptations such as heat tolerance mechanisms like the SLICK gene in cattle and fat tails in sheep and disease resistance traits like trypanotolerance is a foundational step in the development of breed improvement programs for the tropics. Crossbreeding programs have utilized this knowledge for decades resulting in great success stories such as the Girolando cattle of Brazil, which are responsible for producing 80% of the country’s milk today. With the development and use of assisted reproductive technologies (ARTs) like artificial insemination, in vitro fertilization & embryo transfer we have the ability to achieve genetic gain at an unprecedented speed. Many cases have demonstrated promising applications of these technologies, with one such study reporting IVF and ET implementation in Kenyan dairy herds could increase monetary gain by 184% while reducing generation intervals by 47%. Overall, strategic implementation of genetic improvement programs, when adapted to the diverse livestock production systems of the developing tropics hold the key to significantly enhancing livestock productivity, improving food security, and overall contributing to more sustainable agricultural systems in East Africa.

  PublisherOA PDFDOI

• Supercontinuum intrinsic fluorescence imaging heralds free view of living systems

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-01-26 · 3 citations

  preprintOpen access

  Optimal imaging strategies remain underdeveloped to maximize information for fluorescence microscopy while minimizing the harm to fragile living systems. Taking hint from the supercontinuum generation in ultrafast laser physics, we generated supercontinuum fluorescence from untreated unlabeled live samples before nonlinear photodamage onset. Our imaging achieved high-content cell phenotyping and tissue histology, identified bovine embryo polarization, quantified aging-related stress across cell types and species, demystified embryogenesis before and after implantation, sensed drug cytotoxicity in real-time, scanned brain area for targeted patching, optimized machine learning to track small moving organisms, induced two-photon phototropism of leaf chloroplasts under two-photon photosynthesis, unraveled microscopic origin of autumn colors, and interrogated intestinal microbiome. The results enable a facility-type microscope to freely explore vital molecular biology across life sciences.

  PublisherOA PDFDOI

• Rumen-protected methionine supplementation alters lipid profile of preimplantation embryo and endometrial tissue of Holstein cows

  Frontiers in Veterinary Science · 2024-01-17 · 5 citations

  articleOpen access

  Our objective is to evaluate the effects of feeding rumen-protected Met (RPM) throughout the transition period and early lactation on the lipid profile of the preimplantation embryos and the endometrial tissue of Holstein cows. Treatments consisted of feeding a total mixed ration with top-dressed RPM (Smartamine ® M, Adisseo, Alpharetta, GA, United States; MET; n = 11; RPM at a rate of 0.08% of DM: Lys:Met = 2.8:1) or not (CON; n = 9, Lys:Met = 3.5:1). Endometrial biopsies were performed at 15, 30, and 73 days in milk (DIM). Prior to the endometrial biopsy at 73 DIM, preimplantation embryos were harvested via flushing. Endometrial lipid profiles were analyzed using multiple reaction monitoring-profiling and lipid profiles of embryos were acquired using matrix assisted laser desorption/ionization mass spectrometry. Relative intensities levels were used for principal component analysis. Embryos from cows in MET had greater concentration of polyunsaturated lipids than embryos from cows in CON. The endometrial tissue samples from cows in MET had lesser concentrations of unsaturated and monounsaturated lipids at 15 DIM, and greater concentration of saturated, unsaturated (specifically diacylglycerol), and monounsaturated (primarily ceramides) lipids at 30 DIM than the endometrial tissue samples from cows in CON. In conclusion, feeding RPM during the transition period and early lactation altered specific lipid classes and lipid unsaturation level of preimplantation embryos and endometrial tissue.

  PublisherOA PDFDOI

• The Use of Assisted Reproductive Technologies to Improve Genetic Selection in Cattle

  2024-01-01 · 1 citations

  book-chapterSenior author
  PublisherDOI

• Human proinsulin production in the milk of transgenic cattle

  Biotechnology Journal · 2024-03-01 · 9 citations

  articleOpen accessCorresponding

  BACKGROUND: The worldwide growing demand for human insulin for treating diabetes could be supplied by transgenic animals producing insulin in their milk. METHODS AND RESULTS: Pseudo-lentivirus containing the bovine β-casein promoter and human insulin sequences was used to produce modified adult fibroblasts, and the cells were used for nuclear transfer. Transgenic embryos were transferred to recipient cows, and one pregnancy was produced. Recombinant protein in milk was evaluated using western blotting and mass spectrometry. One transgenic cow was generated, and in milk analysis, two bands were observed in western blotting with a molecular mass corresponding to the proinsulin and insulin. The mass spectrometry analysis showed the presence of human insulin more than proinsulin in the milk, and it identified proteases in the transgenic milk that could convert proinsulin into insulin and insulin-degrading enzyme that could degrade the recombinant protein. CONCLUSION: The methodologies used for generating the transgenic cow allowed the detection of the production of recombinant protein in the milk at low relative expression compared to milk proteins, using mass spectrometry, which was efficient for detecting recombinant protein with low expression in milk. Milk proteases could act on protein processing converting recombinant protein to functional protein. On the other hand, some milk proteases could act in degrading the recombinant protein.

  PublisherOA PDFDOI

Recent grants

• NIH Grant F32HD007025

  NIH · $25k

• Amniotic Membrane Derived Matrix for Large Bone Defect Repair

  NIH · $660k · 2018–2022

Frequent coauthors

• M. Rubessa

  Genus (United Kingdom)

  64 shared

• Elisa Lo Monaco

  34 shared

• W.L. Hurley

  University of Illinois Urbana-Champaign

  31 shared

• David J. Beebe

  University of Wisconsin Carbone Cancer Center

  30 shared

• Amy L. Reeder

  30 shared

• Zhi Liu

  East China Jiaotong University

  28 shared

• Derek J. Milner

  University of Illinois Urbana-Champaign

  26 shared

• Massimo Bionaz

  Oregon State University

  26 shared

Education

• NIH NRSA Fellow, Endocrinology and Reproductive Physiology Program

  University of Wisconsin–Madison

  1989

• NIH Post-Doctoral Fellow, Internal Medicine - Endocrinology and Metabolism

  University of Virginia

  1988

• Ph.D., Physiology and Biophysics

  Colorado State University

  1985

• Master's of Science, Animal Sciences

  University of California, Davis

  1979

• Bachelor's of Science, Animal Sciences

  University of California, Davis

  1977