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Article

Novel Metformin-Encapsulating Poly(lactic-co-glycolic acid) Microspheres in Calcium Phosphate Pulp-Capping Cement with Dental Pulp Stem Cells for Regenerative Applications

1
Dental Biomedical Sciences Ph.D. Program, Graduate School, University of Maryland, Baltimore, MD 21201, USA
2
Department of Biomaterials and Regenerative Dental Medicine, University Maryland School of Dentistry, Baltimore, MD 21201, USA
3
Department of Restorative Dental Sciences, University of Ha’il, Hail 55475, Saudi Arabia
4
Department of Restorative Dental Science, College of Dentistry, King Saud University, Riyadh 11545, Saudi Arabia
5
Department of Conservative Dental Sciences, College of Dentistry, Prince Sattam bin Abdulaziz University, Alkharj 11942, Saudi Arabia
6
Department of Restorative Dental Sciences, College of Dentistry, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi Arabia
7
Department of Pediatric Dentistry and Orthodontics Sciences, College of Dentistry, King Khalid University, Abha 62521, Saudi Arabia
8
Department of Oncology and Diagnostic Sciences, School of Dentistry, University of Maryland, Baltimore, MD 21201, USA
9
Department of Neural and Pain Sciences, School of Dentistry, Center to Advance Chronic Pain Research, University of Maryland, Baltimore, MD 21201, USA
10
Marlene and Stewart Greenebaum Cancer Center, School of Medicine, University of Maryland, Baltimore, MD 21201, USA
11
Center for Stem Cell Biology & Regenerative Medicine, School of Medicine, University of Maryland, Baltimore, MD 21201, USA
*
Authors to whom correspondence should be addressed.
Current address: Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH 43210, USA.
Materials 2026, 19(3), 487; https://doi.org/10.3390/ma19030487
Submission received: 20 December 2025 / Revised: 15 January 2026 / Accepted: 23 January 2026 / Published: 26 January 2026

Abstract

Metformin is a promising small molecule for dentin regeneration, but an effective local delivery system for pulp applications has been underexplored. This study encapsulated metformin in poly(lactic-co-glycolic acid) (PLGA) microspheres and incorporated them into calcium phosphate–chitosan cement (CPCC) as a direct pulp-capping material (DPC). Metformin-PLGA microspheres were prepared by double emulsion and mixed with CPCC at a concentration of 0% to 20% by weight. Microsphere morphology, encapsulation efficiency, chemical composition, and physico-mechanical properties were characterized, and compatibility with human dental pulp stem cells (hDPSCs) was evaluated by live/dead assay and SEM. The microspheres were spherical (5.43 ± 0.17 µm) with (51 ± 3.69%) encapsulation efficiency, and FTIR confirmed metformin incorporation. The 15% Met-PLGA-CPCC group showed flexural strength (15.22 ± 1.98 MPa), elastic modulus (4.60 ± 0.73 GPa), and work of fracture (104.96 ± 12.48 J/m2) comparable to or higher than CPCC and MTA, while all Met-PLGA-CPCC groups had shorter setting times ranging from 18 min to 27 min than CPCC (39.15 ± 2.10 min) and MTA (123 ± 4.2 min). Metformin release increased proportionally with Met-PLGA content. hDPSCs exhibited good attachment and high viability on all materials over the evaluated period. In conclusion, Met-PLGA-CPCC provides fast-setting and favorable physico-mechanical properties, sustained metformin delivery, and excellent hDPSC compatibility. These properties support its potential as a bioactive direct pulp-capping material and as a versatile platform for regenerative applications.
Keywords: metformin; direct pulp capping; biomaterial; tissue regeneration metformin; direct pulp capping; biomaterial; tissue regeneration
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MDPI and ACS Style

Alenizy, M.; Alhussein, A.; Almutairi, N.; Ba-Armah, I.; Alqarni, H.; Altamimi, Y.; Altamimi, A.; Ma, T.; Chung, M.-K.; Weir, M.D.; et al. Novel Metformin-Encapsulating Poly(lactic-co-glycolic acid) Microspheres in Calcium Phosphate Pulp-Capping Cement with Dental Pulp Stem Cells for Regenerative Applications. Materials 2026, 19, 487. https://doi.org/10.3390/ma19030487

AMA Style

Alenizy M, Alhussein A, Almutairi N, Ba-Armah I, Alqarni H, Altamimi Y, Altamimi A, Ma T, Chung M-K, Weir MD, et al. Novel Metformin-Encapsulating Poly(lactic-co-glycolic acid) Microspheres in Calcium Phosphate Pulp-Capping Cement with Dental Pulp Stem Cells for Regenerative Applications. Materials. 2026; 19(3):487. https://doi.org/10.3390/ma19030487

Chicago/Turabian Style

Alenizy, Mohammad, Abdullah Alhussein, Nader Almutairi, Ibrahim Ba-Armah, Heba Alqarni, Yazeed Altamimi, Ayman Altamimi, Tao Ma, Man-Kyo Chung, Michael D. Weir, and et al. 2026. "Novel Metformin-Encapsulating Poly(lactic-co-glycolic acid) Microspheres in Calcium Phosphate Pulp-Capping Cement with Dental Pulp Stem Cells for Regenerative Applications" Materials 19, no. 3: 487. https://doi.org/10.3390/ma19030487

APA Style

Alenizy, M., Alhussein, A., Almutairi, N., Ba-Armah, I., Alqarni, H., Altamimi, Y., Altamimi, A., Ma, T., Chung, M.-K., Weir, M. D., Schneider, A., & Xu, H. H. K. (2026). Novel Metformin-Encapsulating Poly(lactic-co-glycolic acid) Microspheres in Calcium Phosphate Pulp-Capping Cement with Dental Pulp Stem Cells for Regenerative Applications. Materials, 19(3), 487. https://doi.org/10.3390/ma19030487

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