AI-Driven Innovation in Tissue Engineering and Regenerative Therapies
Presentation number: PP61
Abstract number: 58-ISABS-2026
THE DEVELOPMENT OF LOAD-RESPONSIVE BIOMATERIAL SCAFFOLDS FOR TARGETED EXTRACELLULAR VESICLE DELIVERY AS A NOVEL CARTILAGE REGENERATION THERAPY
Kugaudaite Gabija1, Lebedis Ignas1, Gasiulyte Eidvyle2, Ciuzas Darius2, Daugelaite Aleja Marija3, Bernotiene Eiva1, Rotomskis Ricardas3,4, Kvederas Giedrius5, Krugly Edvinas2, Uzieliene Ilona1,2
1Department of Regenerative Medicine, Innovative Medicine Centre, Vilnius, Lithuania; 2Kaunas University of Technology, Kaunas, Lithuania; 3Biomedical Physics Laboratory, National Cancer Institute, Vilnius, Lithuania; 4Biophotonics Group, Laser Research Center, Vilnius University, Vilnius, Lithuania; 5Vilnius University Santaros Hospital, Vilnius, Lithuania
gabija.kugaudaite@gmail.com
Osteoarthritis (OA) is a major cause of disability worldwide, lacking effective regenerative therapies. Precision medicine approaches in cartilage repair require controlled, localized delivery of bioactive factors adapted to the joint microenvironment. This study aimed to develop a load-responsive biomaterial scaffold enabling targeted delivery of extracellular vesicles (EVs) derived from menstrual blood–derived stromal cells (MenSCs). MenSCs were isolated and expanded in vitro, and their EVs were incorporated into surface-engineered polycaprolactone scaffolds designed to mimic cartilage structure and mechanical properties. Human bone marrow–derived mesenchymal stromal cells and chondrocytes were seeded onto scaffolds to evaluate cytocompatibility and regenerative potential. Constructs were subjected to dynamic compression to simulate the OA joint environment. Under mechanical stimulation, EV-loaded scaffolds demonstrated enhanced and sustained release compared to static conditions. The system supported high cytocompatibility and promoted chondrogenic differentiation, as evidenced by increased expression of cartilage-specific markers in mesenchymal stromal cells and chondrocytes. Notably, this effect was further enhanced in EV-functionalized scaffolds under mechanical load. These findings demonstrate that biomechanical cues can regulate therapeutic delivery and enhance regenerative outcomes. This study presents a smart, adaptive platform integrating biomaterials and EV-based therapy, advancing precision regenerative medicine. Load-responsive scaffolds represent a promising strategy for personalised cartilage repair with controlled, stimulus-driven therapeutic activity. Funding: Lithuanian Research Council, Postdoctoral Programme (P-PD-24-167, agreement No. S-PD-24-114).
Keywords: precision medicine, regenerative medicine, biomaterials, extracellular vesicles, osteoarthritis
Presentation number: PP62
Abstract number: 50-ISABS-2026
CHLOROGENIC ACID PRESERVES CHONDROCYTE VIABILITY BY MODULATING BCL-2 DEPENDENT APOPTOSIS AND INFLAMMASOME ACTIVATION
Kulyar Muhammad Fakhar-e-Alam1, Hasan Mohammad Mehedi1, Kaboli Saeed1, Akhtar Muhammad2, Bernotiene Eiva1
1Department of Regenerative Medicine, State Research Institute Centre for Innovative Medicine, Vilnius, Lithuania; 2Institute of Clinical Immunology and Allergology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czechia
muhammad.fakhar@imcentras.lt
Cartilage degeneration in growth plates arises from uncontrolled apoptosis and inflammasome activation of chondrocytes. We examined whether pharmacological reinforcement of the anti-apoptotic regulator B cell lymphoma-2 (Bcl-2) could break this pathogenic loop. In vivo, thiram fed broiler chickens were randomized to control, toxin, or chlorogenic-acid (CGA) rescue groups, while in vitro primary chondrocytes were transfected with miR-460a mimic/inhibitor or siBcl-2 and exposed to CGA. Bcl-2 axis modulation was confirmed by RT-qPCR, Western blotting, and immunofluorescence; mitochondrial integrity, cytochrome-c efflux, caspase-3/-7 cleavage, and IL-1β maturation were quantified, and apoptosis was profiled by Annexin V/PI flow cytometry. Thiram suppressed Bcl-2 and obliterated vascularization of the hypertrophic zone, doubling apoptotic chondrocytes (p < 0.01). Genetic silencing of Bcl-2 or over expression of miR- 460a replicated this phenotype in culture, elevating cytochrome c release by 2.4 fold and caspase-3/-7 activity by 2.1 fold, whereas Bcl-2 over expression blunted these signals. CGA restored Bcl-2 protein both in vivo and in vitro, reduced mitochondrial permeabilization, and cut apoptosis by 55% while halving IL-1β maturation (p < 0.01). The co-delivery of CGA with siBcl-2 markedly attenuated the siRNA’s pro-apoptotic effect, implicating CGA-driven post transcriptional stabilization of the Bcl-2 pathway. Collectively, these data identify CGA as a potent small molecule shield that preserves chondrocyte viability by reinforcing Bcl- 2 dependent control of the mitochondrial apoptosis and inflammasome axis. Which offers a tractable, low toxicity strategy for precision regenerative therapy in growth plate disorders.
Keywords: chlorogenic acid, Bcl-2 signaling, chondrocyte apoptosis, inflammasome, regenerative therapy
Presentation number: PP63
Abstract number: 97-ISABS-2026
GRADED MODULATION OF HNF1A REVEALS DOSE-DEPENDENT CHANGES IN THE PANCREATIC BETA CELL N-GLYCOME
Lukšić Fran1, Vičić Bočkor Vedrana1, Šimunović Jelena1, Zoldoš Vlatka1,2
1Genos Glycoscience Research Laboratory, Zagreb, Croatia; 2Faculty of Science, University of Zagreb, Zagreb, Croatia
fluksic@genos.hr
HNF-1α is an essential transcription factor in the development and regulation of beta cell functions. Beta cells are key for proper glucose metabolism regulation and their impaired function or cell death leads to the development of diabetes, a disease now impacting almost 10% of the global population. Mutations in HNF1A cause the monogenic diabetes MODY3, but also contribute to type 2 diabetes risk. HNF-1α regulates a wide range of key pathways, including glycosylation, a post-translational modification that affects protein stability, localization, and function. Due to its complex regulatory network and analytical challenges, beta cell glycosylation has been severely understudied. To fill this gap, we created a beta cell model based on EndoC-βH1 cells stably integrating dCas9-KRAB or dCasMINI-VPR fusions. This system enables us to precisely modulate the expression of genes of interest. By targeting HNF1A with varying numbers of gRNAs, we generated a gradient of expression ranging from mild knockdown to almost complete silencing. Interestingly, mild silencing of HNF1A led to increased sialylation and complex branching, pointing toward a potential cell defense mechanism as a first response to stress. Similar increases in sialylation have been previously described in other cell types as a protective response to inflammation and environmental stress. In contrast, more severe silencing did not further increase these levels, but rather led to slight decrease compared to control levels. This trend may suggest that beta cells attempt to protect themselves by modifying their glycome during early stress exposure; however, as stress becomes more severe (notably HNF1A knockout causes EndoC-BH1 apoptosis) this protective signature appears to diminish. These preliminary observations demonstrate how the same gene can have profoundly different effects on glycosylation depending on its expression level.
Keywords: HNF1A, pancreatic beta cells, EndoC-βH1, CRISPRi/a, N-glycosylation
Presentation number: PP64
Abstract number: 103-ISABS-2026
STANDARDIZED SINGLE-INJECTION LEUKOCYTE-RICH VERSUS LEUKOCYTE-POOR PLATELET-RICH PLASMA FOR MILD-TO-MODERATE KNEE OSTEOARTHRITIS
Pavelić Eduard1,2, Bulić Luka1,2,3, Škaro Vedrana4, Brlek Petar1,2,5, Molnar Vilim1,2, Karli David14,15, Primorac Dragan1,8,9,10,7,6,11,12,13,4
1St. Catherine Specialty Hospital, Zagreb, Croatia; 2School of Medicine, Josip Juraj Strossmayer University of Osijek, Osijek, Croatia; 3Algebra Bernays University, Zagreb, Croatia; 4International Center for Applied Biological Research, Zagreb, Croatia; 5Department of Molecular Biology, Faculty of Science, University of Zagreb, Zagreb, Croatia; 6Faculty of Dental Medicine and Health, Josip Juraj Strossmayer, University of Osijek, Osijek, Croatia; 7Gandhinagar Campus, National Forensic Sciences University, Gandhinagar, India; 8University of Split, School of Medicine, Split, Croatia; 9Eberly College of Science, The Pennsylvania State University, State College, Pennsylvania, PA, United States of America; 10The Henry C. Lee College of Criminal Justice and Forensic Sciences, University of New Haven, New Haven, CT, United States of America; 11Sana Kliniken Oberfranken, Coburg, Germany; 12School of Medicine, University of Rijeka, Rijeka, Croatia; 13School of Medicine, University of Pittsburgh, Pennsylvania, PA, United States of America; 14Greyledge Technologies, Miami, FL, United States of America; 15Karli Center, Miami, FL, United States of America
eduard.pavelic@gmail.com
Current literature suggests that leukocyte-poor platelet-rich plasma may provide better clinical outcomes than leukocyte-rich formulations in knee osteoarthritis, yet uncertainty remains when both products are prepared as standardized, high-dose PRP. The aim of this randomized double-blind study was to compare standardized leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP) in patients with mild-to- moderate knee osteoarthritis and to determine whether leukocyte content influences outcome when platelet dose is quantified. Adults with symptomatic Kellgren-Lawrence grade 1-3 knee osteoarthritis received a single ultrasound-guided intra-articular injection of LR-PRP or LP-PRP and were followed for 12 months. Clinical outcomes were assessed at baseline and at 1, 3, 6, and 12 months using VAS, WOMAC, and KOOS scores. Both groups showed significant longitudinal improvement in pain, stiffness, function, sport/recreation, and knee-related quality of life. The greatest improvement was observed early after treatment and was maintained through 12 months. No statistically significant differences were found between LR-PRP and LP-PRP at any follow-up time point for the principal outcomes. Exploratory analyses also showed no significant difference in thrombocyte values between groups and no significant difference in responder rates between LR-PRP and LP-PRP. In conclusion, when administered as a single injection using a standardized and quantified protocol, both LR-PRP and LP-PRP provided significant and durable clinical benefit in mild-to-moderate knee osteoarthritis, without evidence of superiority of either leukocyte profile. These findings highlight the importance of PRP standardization and platelet-dose reporting in future clinical studies.
Keywords: knee osteoarthritis, platelet-rich plasma, leukocyte-rich PRP, leukocyte-poor PRP, orthobiologics
Presentation number: PP65
Abstract number: 78-ISABS-2026
DEVELOPMENT OF A PATIENT-SPECIFIC MECHANICAL FINGER PROSTHESIS BASED ON MULTI-MATERIAL ADDITIVE MANUFACTURING
Szczygieł Paweł1
1Kielce University of Technology, Kielce, Poland
pszczygiel@tu.kielce.pl
This work presents the design and fabrication of a personalized mechanical finger prosthesis developed based on the patient’s body geometry. The device was designed as a tendon-driven system, enabling finger motion through a cable (tendon) mechanism that translates external actuation into functional grasping movement. The prosthesis was manufactured using multi-material additive manufacturing, combining a rigid nanocomposite polylactic acid (PLA) reinforced with copper (PLA-Cu) for structural components and thermoplastic polyurethane (TPU) for flexible functional elements. This combination enabled the integration of stiffness and elasticity within a single fabrication process, improving both structural stability and user interaction. The proposed design methodology emphasizes patient-specific geometry acquisition and direct digital adaptation of functional prosthetic systems, enabling rapid customization without the need for traditional tooling. Particular attention was given to the integration of compliant elements to enhance grip performance and user comfort. The developed prosthesis was tested in real conditions by the end user, confirming its functional effectiveness and satisfactory usability. This work was created as a result of the research project no. 2024/53/N/ST8/01291, titled Experimental analysis of manufacturing methods for flexible coatings used to enhance the performance of hand prosthesis components, funded by the National Science Centre, Poland.
Keywords: finger prosthesis, patient-specific design, additive manufacturing, tendon-driven mechanism, TPU
Presentation number: PP66
Abstract number: 114-ISABS-2026
STEM CELL THERAPY IN PATIENTS WITH PERIPHERAL ARTERIAL DISEASE
Vicković Dominik1, Duliba Iva1, Hader Josip2, Budinčević Hrvoje3, Zadro Zvonko1,2, Ivkošić Ante2,1
1Department of Surgery, Clinical Hospital “Sveti Duh”, Zagreb, Croatia; 2School of medecine, University of Zagreb, Zagreb, Croatia; 3Department of Neurology, Clinical Hospital “Sveti Duh”, Zagreb, Croatia
dominikvickovic@gmail.com
Peripheral arterial disease (PAD) affects over 65% of patients over 60 and results mainly from atherosclerosis of lower limb arteries, causing obstructed blood flow. Clinical manifestations range from intermittent claudications to critical limb ischemia (CLI), with 10-40% of CLI patients undergoing major limb amputation within six months of diagnosis. Revascularization including surgery or endovascular treatment is mandatory, whilst 20-45% of CLI patients are ineligible, defining the “no-option” group with poor prognosis. This highlights the need for novel therapies, with stem cell therapy emerging as a potential option. This review aimed to assess whether stem cell therapy can enhance quality of life in no-option patients. A narrative review of relevant biomedical literature was conducted using predefined search terms. Stem cells exert therapeutic effects primarily through paracrine signaling, promoting angiogenesis, modulating inflammation, and enhancing tissue repair via secretion of growth factors such as VEGF and cytokines. They may also improve microvascular perfusion and endothelial function in ischemic tissues. The literature indicates autologous stem cell therapy benefits no-option patients, outperforming conventional treatment in ulcer healing, pain-free walking distance, rest pain reduction, and hemodynamic measures such as ankle-brachial index and transcutaneous oxygen pressure. In conclusion, stem cell therapy shows potential in improving outcomes for no-option PAD patients. Nevertheless, long-term benefits remain unconfirmed, and evidence quality is low, influenced by cell type, dose, and administration route. Given the high morbidity and mortality in this population, discontinuing this therapy would be premature. Further placebo-controlled, multicenter phase 3 trials with long-term follow-up are needed to establish stem cell therapy as standard treatment for CLI in no-option patients.
Keywords: angiogenesis, critical limb ischemia, limb amputation, peripheral arterial disease, stem cell therapy
Published: June 16th, 2026.
Copyright: © 2026 Authors of AI-Driven Innovation in Tissue Engineering and Regenerative Therapies section. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
