The use of scaffolds for osteochondral tissue regeneration requires an appropriate selection of materials and manufacturing techniques that provide the basis for supporting both cartilage and bone tissue formation. As scaffolds are designed to replicate a part of the replaced tissue and ensure cell growth and differentiation, implantable materials have to meet various biological requirements, e.g., biocompatibility, biodegradability, and mechanical properties. Osteoconductive materials such as tricalcium phosphate ceramics and some biodegradable polymers appear to be a perfect choice. The present work evaluates the structural, mechanical, thermal, and functional properties of a shape memory terpolymer modified with β-tricalcium phosphate (β-TCP). A new approach is using the developed materials for 4D printing, with a particular focus on its applicability in manufacturing medical implants. In this study, the manufacturing parameters of the scaffold components were developed. The scaffolds were examined via scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and mechanical testing. The cytotoxicity result was obtained with an MTT assay, and the alkaline phosphatase (ALP) activity was measured. The structural and microstructural investigations confirmed the integration of β-TCP into the filament matrix and scaffolds. Thermal stability was enhanced as β-TCP delayed depolymerization of the polymer matrix. The shape memory studies demonstrated effective recovery. The in vitro cell culture studies revealed the significantly increased cell viability and alkaline phosphatase (ALP) activity of the β-TCP-modified terpolymer after 3 weeks. The developed terpolymer can be tailored for applications in which partial shape recovery is acceptable, such as bone scaffolds.

Department of Ceramics and Refractories Faculty of Materials Science and Ceramics AGH University of Krakow 30 059 Kraków Poland

Department of Glass Technology and Amorphous Coatings Faculty of Materials Science and Ceramics AGH University of Krakow 30 059 Kraków Poland

Department of Mechanical Engineering Fundamentals Faculty of Mechanical Engineering and Computer Science University of Bielsko Biala 43 300 Bielsko Biała Poland

Department of Medical Chemistry and Biochemistry Faculty of Medicine and Dentistry Palacký University Olomouc 779 00 Olomouc Czech Republic

Faculty of Materials Civil and Environmental Engineering University of Bielsko Biala 43 300 Bielsko Biała Poland

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Asensio G., Benito-Garzón L., Ramírez-Jiménez R.A., Guadilla Y., Gonzalez-Rubio J., Abradelo C., Parra J., Martín-López M.R., Aguilar M.R., Vázquez-Lasa B., et al. Biomimetic Gradient Scaffolds Containing Hyaluronic Acid and Sr/Zn Folates for Osteochondral Tissue Engineering. Polymers. 2022;14:12. doi: 10.3390/polym14010012. PubMed DOI PMC

Rajzer I., Menaszek E., Bacakova L., Orzelski M., Błażewicz M. Hyaluronic acid-coated carbon nonwoven fabrics as potential material for repair of osteochondral defects. Fibres Text. East. Eur. 2013;99:102–107.

Loureiro J.A., Pereira M.C. PLGA based drug carrier and pharmaceutical applications: The most recent advances. Pharmaceutics. 2020;12:903. doi: 10.3390/pharmaceutics12090903. PubMed DOI PMC

Rajzer I., Kurowska A., Frankova J., Sklenářová R., Nikodem A., Dziadek M., Jabłoński A., Janusz J., Szczygieł P., Ziąbka M. 3D-Printed Polycaprolactone Implants Modified with Bioglass and Zn-Doped Bioglass. Materials. 2023;16:1061. doi: 10.3390/ma16031061. PubMed DOI PMC

Long J., Nand A., Ray S. Application of Spectroscopy in Additive Manufacturing. Materials. 2021;14:203. doi: 10.3390/ma14010203. PubMed DOI PMC

Novotná R., Franková J. Materials suitable for osteochondral regeneration. ACS Omega. 2024;9:30097–30108. doi: 10.1021/acsomega.4c04789. PubMed DOI PMC

Demoly F., Dunn M.L., Wood K.L., Qi H.J., André J.C. The status, barriers, challenges, and future in design for 4D printing. Mater. Des. 2021;212:110193. doi: 10.1016/j.matdes.2021.110193. DOI

Jolaiy S., Yousefi A., Hosseini M., Zolfagharian A., Demoly F., Bodaghi M. Limpet-inspired design and 3D/4D printing of sustainable sandwich panels: Pioneering supreme resiliency, recoverability and repairability. Appl. Mater. Today. 2024;38:102243. doi: 10.1016/j.apmt.2024.102243. DOI

Doostmohammadi H., Kashmarizad K., Baniassadi M., Bodaghi M., Mostafa Baghani M. 4D printing and optimization of biocompatible poly lactic acid/poly methyl methacrylate blends for enhanced shape memory and mechanical properties. J. Mech. Behav. Biomed. Mater. 2024;160:106719. doi: 10.1016/j.jmbbm.2024.106719. PubMed DOI

Skubis-Sikora A., Hudecki A., Sikora B., Wieczorek P., Hermyt M., Hreczka M., Likus W., Markowski J., Siemianowicz K., Kolano-Burian A., et al. Toxicological Assessment of Biodegradable Poli-ε-Caprolactone Polymer Composite Materials Containing Hydroxyapatite, Bioglass, and Chitosan as Potential Biomaterials for Bone Regeneration Scaffolds. Biomedicines. 2024;12:1949. doi: 10.3390/biomedicines12091949. PubMed DOI PMC

Spearman B.S., Agrawal N.K., Rubiano A., Simmons C.S., Mobini S., Schmidt C.E. Tunable methacrylated hyaluronic acid-based hydrogels as scaffolds for soft tissue engineering applications. J. Biomed. Mater. Res. Part A. 2020;108:279–291. doi: 10.1002/jbm.a.36814. PubMed DOI PMC

Rajzer I., Rom M., Błażewicz M. Production of carbon fibers modified with ceramic powders for medical applications. Fibers Polym. 2010;11:615–624. doi: 10.1007/s12221-010-0615-8. DOI

Helaehil J.V., Lourenço C.B., Huang B., Helaehil L.V., de Camargo I.X., Chiarotto G.B., Santamaria-Jr M., Bártolo P., Caetano G.F. In Vivo Investigation of Polymer-Ceramic PCL/HA and PCL/β-TCP 3D Composite Scaffolds and Electrical Stimulation for Bone Regeneration. Polymers. 2022;14:65. doi: 10.3390/polym14010065. PubMed DOI PMC

Esslinger S., Grebhardt A., Jaeger J., Kern F., Killinger A., Bonten C., Gadow R. Additive Manufacturing of β-Tricalcium Phosphate Components via Fused Deposition of Ceramics (FDC) Materials. 2021;14:156. doi: 10.3390/ma14010156. PubMed DOI PMC

Ghezzi B., Matera B., Meglioli M., Rossi F., Duraccio D., Faga M.G., Zappettini A., Macaluso G.M., Lumetti S. Composite PCL Scaffold With 70% β-TCP as Suitable Structure for Bone Replacement. Int. Dent. J. 2024;74:1220–1232. doi: 10.1016/j.identj.2024.02.013. PubMed DOI PMC

Orchel A., Jelonek K., Kasperczyk J., Dobrzynski P., Marcinkowski A., Pamula E., Orchel J., Bielecki I., Kulczycka A. The Influence of Chain Microstructure of Biodegradable Copolyesters Obtained with Low-Toxic Zirconium Initiator to In Vitro Biocompatibility. BioMed Res. Int. 2013;2013:176946. doi: 10.1155/2013/176946. PubMed DOI PMC

Smola A., Dobrzynski P., Cristea M., Kasperczyk J., Sobota M., Gebarowska K., Janeczeka H. Bioresorbable terpolymers based on l-lactide, glycolide and trimethylene carbonate with shape memory behavior. Polym. Chem. 2014;5:2442–2452. doi: 10.1039/c3py01557b. DOI

Formas K., Kurowska A., Janusz J., Szczygieł P., Rajzer I. Injection Molding Process Simulation of Polycaprolactone Sticks for Further 3D Printing of Medical Implants. Materials. 2022;15:7295. doi: 10.3390/ma15207295. PubMed DOI PMC

Pivodová V., Franková J., Doležel P., Ulrichová J. The response of oste-oblast-like SaOS-2 cells to modified titanium surfaces. Int. J. Oral Maxillofac. Implants. 2013;28:1386–1394. doi: 10.11607/jomi.3039. PubMed DOI

Chen Z., Zhang X., Fu Y., Jin Y., Weng Y., Bian X., Chen X. Degradation Behaviors of Polylactic Acid, Polyglycolic Acid, and Their Copolymer Films in Simulated Marine Environments. Polymers. 2024;16:1765. doi: 10.3390/polym16131765. PubMed DOI PMC

Vey E., Rodger C., Booth J., Claybourn M., Miller A.F., Saiani A. Degradation kinetics of poly(lactic-co-glycolic) acid block copolymer cast films in phosphate buffer solution as revealed by infrared and Raman spectroscopies. Polym. Degrad. Stab. 2011;96:1882–1889. doi: 10.1016/j.polymdegradstab.2011.07.011. DOI

Al-Qahtani A.S., Tulbah H.I., Binhasan M., Shabib S., Al-Aali K.A., Alhamdan M.M., Abduljabbar T. Influence of Concentration Levels of β-Tricalcium Phosphate on the Physical Properties of a Dental Adhesive. Nanomaterials. 2022;12:853. doi: 10.3390/nano12050853. PubMed DOI PMC

Jung Y., Lee S.H., Kim S.H., Lim J.C., Kim S.H. Synthesis and characterization of the biodegradable and elastic terpolymer poly(glycolide-co-l-lactide-co-ϵ-caprolactone) for mechanoactive tissue engineering. J. Biomater. Sci. Polym. Ed. 2013;24:386–397. doi: 10.1080/09205063.2012.690281. PubMed DOI

Kim D., Kim K.H., Yang Y.S., Jang K.S., Jeon S., Jun-Ho Jeong J.H., Park S.A. 4D printing and simulation of body temperature-responsive shape-memory polymers for advanced biomedical applications. Int. J. Bioprint. 2024;10:3035. doi: 10.36922/ijb.3035. DOI

Senatov F., Niaza K., Zadorozhnyy M.Y., Maksimkin A., Kaloshkin S., Estrin Y. Mechanical properties and shape memory effect of 3D-printed PLA-based porous scaffolds. J. Mech. Behav. Biomed. Mater. 2016;57:139–148. doi: 10.1016/j.jmbbm.2015.11.036. PubMed DOI

Zarek M., Mansour N., Shapira S., Cohn D. 4D printing of shape memory-based personalized Endoluminal medical devices. Macromol. Rapid Commun. 2017;38:1600628. doi: 10.1002/marc.201600628. PubMed DOI

Thérien-Aubin H.L., Wu Z.L., Nie Z., Kumacheva E. Multiple shape transformations of composite hydrogel sheets. J. Am. Chem. Soc. 2013;135:4834–4839. doi: 10.1021/ja400518c. PubMed DOI

Hippler M., Blasco E., Qu J., Tanaka M., Barner-Kowollik C., Wegener M., Bastmeyer M. Controlling the shape of 3D microstructures by temperature and light. Nat. Commun. 2019;10:232. doi: 10.1038/s41467-018-08175-w. PubMed DOI PMC

Prakash A., Malviya R., Sridhar S.B., Shareef J. 4D printing in dynamic and adaptive bone implants: Progress in bone tissue engineering. Bioprinting. 2024;44:e00373. doi: 10.1016/j.bprint.2024.e00373. DOI

Lui Y.S., Sow W.T., Tan L.P., Wu Y., Lai Y., Li H. 4D printing and stimuli-responsive materials in biomedical aspects. Acta Biomater. 2019;92:19–36. doi: 10.1016/j.actbio.2019.05.005. PubMed DOI

Lu T., Liang Y., Zhang L., Yuan X., Ye J. Fabrication of β-TCP ceramic scaffold with hierarchical pore structure using 3D printing and porogen: Investigation of osteoinductive and bone defects. Appl. Mater. Today. 2024;40:102351. doi: 10.1016/j.apmt.2024.102351. DOI