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Biomedicines
Volume 13
Issue 12
10.3390/biomedicines13123039
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Article

CAPE Derivatives as Potent Agents for Induction of Osteogenic Differentiation in DPSCs and Biomaterial Development

by
Marwa Balaha
1,2,*,
Barbara De Filippis
1,*,
Monica Rapino
3,
Paulina Kazimierczak
4,
Agata Przekora
4,
Tamer Esmail
5,
Eleonora Chiara Toto
1,
Giulia Petrucci
1,
Cristina Canal
6,
Amelia Cataldi
1 and
Viviana di Giacomo
1,7
1
Department of Pharmacy, University “G. d’Annunzio”, Chieti-Pescara, 66100 Chieti, Italy
2
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33511, Egypt
3
Unit of Chieti, Genetic Molecular Institute of CNR, “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy
4
Department of Tissue Engineering and Regenerative Medicine, Medical University of Lublin, 20-059 Lublin, Poland
5
Department of Medicine and Aging Sciences, University “G. d’Annunzio”, Chieti-Pescara, 66100 Chieti, Italy
6
Department of Materials Science and Engineering and Research Centre for Biomedical Engineering, Universitat Politècnica de Catalunya—BarcelonaTech (UPC), 08034 Barcelona, Spain
7
UdA-TechLab, Research Center, University “G. d’Annunzio”, Chieti-Pescara, 66100 Chieti, Italy
*
Authors to whom correspondence should be addressed.
Biomedicines 2025, 13(12), 3039; https://doi.org/10.3390/biomedicines13123039 (registering DOI)
Submission received: 1 November 2025 / Revised: 21 November 2025 / Accepted: 5 December 2025 / Published: 10 December 2025
(This article belongs to the Collection Feature Papers in Biomedical Materials)
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Abstract

Objectives: Bone defects, resulting from many causes, represent a challenge in maxillofacial and orthopedic surgery. Regenerative medicine offers promising strategies by introducing exogenous materials to modify the tissue environment and modulate the body’s natural healing mechanisms. Dental pulp stem cells (DPSCs) are considered an effective source for tissue repair. Small molecules such as caffeic acid phenethyl ester (CAPE), although having promising effects in promoting bone regeneration, are characterized by low chemical stability, which impairs their clinical application. This study aimed to investigate the bone regenerative capability of four CAPE derivatives, recently synthesized in our laboratory and selected based on previous studies. Methods: DPSCs were induced to osteogenic differentiation in the presence of these compounds (0–5 μM), and cell viability, matrix deposition, alkaline phosphatase activity, and osteogenic marker gene expression were evaluated. In addition, bone biomaterials composed of a chitosan/agarose matrix reinforced with nanohydroxyapatite and enriched with these CAPE derivatives were fabricated and assessed for cytotoxicity and cell adhesion. Results: Two of the tested compounds effectively enhanced DPSC differentiation toward the osteogenic lineage. The fabricated bone biomaterials showed no cytotoxicity and supported cell adhesion. Furthermore, these compounds demonstrated stability under various conditions, confirming their suitability for incorporation into bone biomaterials. Conclusions: The tested CAPE derivatives exhibit promising osteoinductive properties and stability, offering a valid alternative to traditional therapeutic strategies in regenerative medicine.
Keywords: bone regeneration; CAPE; DPSC; biomaterial; stability; natural compounds; synthetic derivatives bone regeneration; CAPE; DPSC; biomaterial; stability; natural compounds; synthetic derivatives
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MDPI and ACS Style

Balaha, M.; De Filippis, B.; Rapino, M.; Kazimierczak, P.; Przekora, A.; Esmail, T.; Toto, E.C.; Petrucci, G.; Canal, C.; Cataldi, A.; et al. CAPE Derivatives as Potent Agents for Induction of Osteogenic Differentiation in DPSCs and Biomaterial Development. Biomedicines 2025, 13, 3039. https://doi.org/10.3390/biomedicines13123039

AMA Style

Balaha M, De Filippis B, Rapino M, Kazimierczak P, Przekora A, Esmail T, Toto EC, Petrucci G, Canal C, Cataldi A, et al. CAPE Derivatives as Potent Agents for Induction of Osteogenic Differentiation in DPSCs and Biomaterial Development. Biomedicines. 2025; 13(12):3039. https://doi.org/10.3390/biomedicines13123039

Chicago/Turabian Style

Balaha, Marwa, Barbara De Filippis, Monica Rapino, Paulina Kazimierczak, Agata Przekora, Tamer Esmail, Eleonora Chiara Toto, Giulia Petrucci, Cristina Canal, Amelia Cataldi, and et al. 2025. "CAPE Derivatives as Potent Agents for Induction of Osteogenic Differentiation in DPSCs and Biomaterial Development" Biomedicines 13, no. 12: 3039. https://doi.org/10.3390/biomedicines13123039

APA Style

Balaha, M., De Filippis, B., Rapino, M., Kazimierczak, P., Przekora, A., Esmail, T., Toto, E. C., Petrucci, G., Canal, C., Cataldi, A., & di Giacomo, V. (2025). CAPE Derivatives as Potent Agents for Induction of Osteogenic Differentiation in DPSCs and Biomaterial Development. Biomedicines, 13(12), 3039. https://doi.org/10.3390/biomedicines13123039

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