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From Idea to Impact: How an ISAKOS Research Grant Enabled High-Quality Orthobiologics Research in a Limited-Resource Setting

Theodorakys Marín Fermín, MD, VENEZUELA

 

ISAKOS eNewsletters   eNewsletter Article 2026   rating

I carried the idea of combining blood flow restriction (BFR) training with platelet-rich plasma (PRP) for many years. It began during my fellowship at TheMIS Orthopaedic Center in Thessaloniki, under the mentorship of Ioannis Terzidis and Emmanouil Papakostas. Dr. Papakostas introduced me to BFR as an exercise rehabilitation modality. While reviewing the literature on BFR for my fellowship scientific project, I was struck by the biomolecules, growth factors, and hormones released in the hypoxic environment created by tourniquets during exercise. I began to wonder whether these effects could be harnessed to modify the composition of PRP.

Later, during my fellowship in Clinical Orthobiologics at Aspetar Hospital in Qatar under Pieter D’Hooghe, I shared and refined the concept with Markus Laupheimer and Mathieu Boudier-Revéret from Aspetar’s Sports Medicine Department. Their input helped mature the idea methodologically. Together, we reviewed how different exercise modalities alter blood composition and how those changes might translate into PRP preparations.

ISAKOS transformed this long-held research idea into reality through programs that deliberately bridge the gap between high-quality science and limited-resource settings. This support aligns directly with the 2024–2027 ISAKOS Strategic Plan, which positions the Society at the forefront of advocating for research “particularly among emerging researchers and in countries with limited resources,” while fostering members’ research ambitions and growing the scientific community. I drew inspiration from many members of the ISAKOS Biologics Committee, including Professors Giuseppe Filardo, Norimasa Nakamura, and Elizaveta Kon, as well as Drs. Fabio Valerio Sciarretta and Alberto Gobbi.

After years of training abroad, I returned to Venezuela and conducted the study with a 100% Venezuelan team at a certified laboratory. Working alongside young doctors and medical students became a cornerstone of my career as both clinician and researcher. The experience encompassed every stage—from conception to dissemination—and reinforced the conviction that an international society can elevate research performed in resource-constrained environments to the highest standards. The US$15,000 ISAKOS grant was invaluable, covering the costly laboratory supplies required for cytokine and hormone screening.

My team included Olivia González (shoulder orthopaedic surgeon), Rafael Melo (medical student), and young doctors Oscar Omaña and María Victoria Romero. They assisted with recruitment in my private practice at Clínica Santa Sofía beginning in late April 2024 and with each experiment and blood draw. Bioanalysts Cassandra Pacheco and María Isabel Mijares, along with their team at the Avilab laboratory, provided outstanding support from June to November 2024. One of the most rewarding aspects was fully involving every team member and ensuring they felt a sense of ownership of a project funded and recognized at the international level.

Recruitment proved to be the greatest challenge due to our strict inclusion criteria. After six months, we completed sample collection and began data curation and interpretation while preparing the manuscript, with statistical support from Fhabián Carrión Nessi and David Forero-Peña of Vacter LLC. The study was published in October 2025 in the Journal of Experimental Orthopaedics. We presented preliminary results at the 15th Biennial ISAKOS Congress in Munich (2025) and the final results at the 18th ICRS World Congress in Boston (2025).

The randomized controlled trial investigated how low-load bilateral knee extensions performed with BFR affected PRP composition—specifically platelet and leukocyte counts and the concentrations of insulin-like growth factor 1 (IGF-1) and interleukin-6 (IL-6). Twenty-four healthy male volunteers aged 18–40 with a Tegner activity level of 5 or higher were randomized to either low-load bilateral knee extensions with BFR or the same exercise without BFR. Blood samples were collected at baseline and at 10, 20, and 30 minutes post-intervention. The BFR protocol consisted of four sets of knee extensions with 30-second rest intervals at 80% limb-occlusion pressure, using 15-lb ankle weights. Analyses included mixed ANOVA and Friedman tests. Key findings included a substantial reduction in IL-6 concentration in the BFR group at all time points (below 1 pg/mL; p = 0.013), contrary to the initial hypothesis. The BFR group showed higher (though not statistically significant) platelet concentration and dose at 10 and 20 minutes, with maximum increases of 9.94% and 15.61%, respectively, at 10 minutes (p = 0.07). Leukocyte concentration and dose decreased by approximately 17–18% at 10 minutes in the BFR group, while the control group experienced increases of roughly 21–24%. A non-significant peak increase of 4.05% in IGF-1 occurred in the BFR group at 20 minutes. Only one participant reported delayed-onset muscle soreness; no other adverse events occurred.

These results suggest that BFR may help tailor PRP composition by reducing pro-inflammatory markers, potentially offering a practical, safe approach for specific musculoskeletal applications.

Over the years of ISAKOS support, I have committed to giving back—through active committee participation, reviewing for the Journal of ISAKOS, and promoting the Society at every local and regional scientific presentation. ISAKOS is far more than a professional organization to me.

I am grateful to the ISAKOS Scientific Committee (Olufemi Ayeni, Ryosuke Kuroda, Yuichi Hoshino, and Jason Koh); the ISAKOS staff (Sarah Corpuz, Rebecca Brun, Hilary Merliner, and Sue Reimbold); my research mentor, Professor Stefano Zaffagnini, who supported both my surgical training as a visiting surgeon at Aspetar and my scientific growth as an Associate Editor of the Journal of Experimental Orthopaedics; and my family, mentors, and friends.

I hope this experience encourages colleagues in South America and around the world—especially those working in limited-resource settings—to engage with ISAKOS and apply for its Research Grants. The Society’s strategic commitment to fostering high-quality research among emerging investigators and in countries with limited resources makes ambitious, impactful science possible. Pursue the ideas that stay with you; with ISAKOS support, they can become reality.

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Figure 1. With Emmanouil Papakostas and Pr. Giuseppe Filardo at the 2025 ISAKOS Congress in Munich, Germany.

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Figure 2. ISAKOS Biologics Committee meeting at the 2025 ICRS World Congress in Boston, USA.

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Figure 3. Our Sports Orthopaedics team, Olivia González and Jenire Leal, at Clinica Santa Sofia in Caracas, Venezuela.

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Figures 4. Conducting experiments at the Avilab Laboratory in Caracas, Venezuela.

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Figure 5. Conducting experiments at the Avilab Laboratory in Caracas, Venezuela.

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Figure 6. Conducting experiments at the Avilab Laboratory in Caracas, Venezuela.

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Figure 7. María Victoria Romero, Óscar Omaña, and Rafael Melo celebrating after concluding the trial.

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Figure 8. With my ISAKOS Research Mentor, Pr. Stefano Zaffagnini, as a visiting surgeon at Aspetar Orthopaedic and Sports Medicine Hospital.

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Figure 9. Presentation of the trial's final results at the 2025 ICRS World Congress in Boston, USA.