{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T10:45:43Z","timestamp":1788691543562,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T00:00:00Z","timestamp":1605052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>One of the main applications of bone graft materials is filling the gap after the surgical removal of bone cancer or tumors. Insufficient healing commonly leads to non-union fracture which could lead to cancer resurgence or infection. Emerging 3D printing of on-demand bone graft biomaterials can deliver personalized solutions with minimized risk of relapse and recurrence of cancer after bone removal surgery. This research aims to explore 3D printed calcium phosphate cement (CPC) based scaffolds as novel anti-cancer drug delivery systems to treat bone cancer. For the study, various 3D printed CPC based scaffolds (diameter 5 mm) with interconnected pores were utilized. Various optimized polymeric solutions containing a model anticancer drug 5-fluorouracil (5-FU) was used to homogenously coat the CPC scaffolds. Both hydrophilic Soluplus (SOL) and polyethylene glycol (PEG) and a combination of both were used to develop stable coating solutions. The surface morphology of the coated scaffolds, observed via SEM, revealed deposition of the polymeric solution represented by a semi-smooth surface as opposed to the blank scaffolds that showed a smoother surface. An advanced surface analysis conducted via confocal microscopy showed a homogenous distribution of the drug throughout the coated scaffolds. Solid-state analysis studied by applying differential scanning calorimetry (DSC) and X-ray diffraction (XRD) revealed semi-crystalline nature of the drug whereas mechanical analysis conducted via texture analysis showed no evidence in the change of the mechanical properties of the scaffolds after polymeric solutions were applied. The FTIR analysis revealed no major intermolecular interactions between 5-FU and the polymers used for coatings except for F2 where a potential nominal interaction was evidenced corresponding to higher Soluplus content in the formulation. In vitro dissolution studies showed that almost 100% of the drug released within 2 h for all scaffolds. Moreover, in vitro cell culture using two different cell lines (Hek293T-human kidney immortalized cell line and HeLa-human bone osteosarcoma epithelial cell line) showed significant inhibition of cell growth as a function of decreased numbers of cells after 5 days. It can be claimed that the developed 5-FU coated 3D printed scaffolds can successfully be used as bone graft materials to potentially treat bone cancer or bone neoplasm and for personalized medical solutions in the form of scaffolds for regenerative medicine or tissue engineering applications.<\/jats:p>","DOI":"10.3390\/pharmaceutics12111077","type":"journal-article","created":{"date-parts":[[2020,11,11]],"date-time":"2020-11-11T20:20:33Z","timestamp":1605126033000},"page":"1077","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":51,"title":["3D Printed Calcium Phosphate Cement (CPC) Scaffolds for Anti-Cancer Drug Delivery"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0470-4908","authenticated-orcid":false,"given":"Yan","family":"Wu","sequence":"first","affiliation":[{"name":"Pharmaceutics Research Laboratory, Arundel Building, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Woodbine","sequence":"additional","affiliation":[{"name":"Sussex Centre for Genome Damage and Stability (GDSC), School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2028-2389","authenticated-orcid":false,"given":"Antony M.","family":"Carr","sequence":"additional","affiliation":[{"name":"Sussex Centre for Genome Damage and Stability (GDSC), School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9RQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit R.","family":"Pillai","sequence":"additional","affiliation":[{"name":"Pharmaceutical Engineering and 3D Printing (PharmE3D) Lab, Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3244-2482","authenticated-orcid":false,"given":"Ali","family":"Nokhodchi","sequence":"additional","affiliation":[{"name":"Pharmaceutics Research Laboratory, Arundel Building, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3373-5586","authenticated-orcid":false,"given":"Mohammed","family":"Maniruzzaman","sequence":"additional","affiliation":[{"name":"Pharmaceutical Engineering and 3D Printing (PharmE3D) Lab, Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, University of Texas at Austin, Austin, TX 78712, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e00034","DOI":"10.1016\/j.bprint.2018.e00034","article-title":"Towards preserving post-printing cell viability and improving the resolution: Past, present, and future of 3D bioprinting theory","volume":"11","author":"Lepowsky","year":"2018","journal-title":"Bioprinting"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/nbt.2958","article-title":"3D bioprinting of tissues and organs","volume":"32","author":"Murphy","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.tibtech.2017.10.015","article-title":"Biofabrication: A Guide to Technology and Terminology","volume":"36","author":"Moroni","year":"2018","journal-title":"Trends Biotechnol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mee.2018.08.004","article-title":"3D Bioprinting and its application to organ-on-a-chip","volume":"200","author":"Park","year":"2018","journal-title":"Microelectron. Eng."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/nbt.3413","article-title":"A 3D bioprinting system to produce human-scale tissue constructs with structural integrity","volume":"34","author":"Kang","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2636","DOI":"10.1002\/adhm.201600483","article-title":"3D Cell Printing of Functional Skeletal Muscle Constructs Using Skeletal Muscle-Derived Bioink","volume":"5","author":"Choi","year":"2016","journal-title":"Adv. Healthc. Mater."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"025034","DOI":"10.1088\/1758-5090\/aa71c8","article-title":"Direct 3D cell-printing of human skin with functional transwell system","volume":"9","author":"Kim","year":"2017","journal-title":"Biofabrication"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.biomaterials.2016.06.012","article-title":"A comprehensive review on droplet-based bioprinting: Past, present and future","volume":"102","author":"Gudapati","year":"2016","journal-title":"Biomaterials"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"119","DOI":"10.18063\/ijb.v1i1.119","article-title":"3D Printing for Drug Manufacturing: A Perspective on the Future of Pharmaceuticals","volume":"4","author":"Lepowsky","year":"2018","journal-title":"Int. J. Bioprinting"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1023\/A:1026394530192","article-title":"Bone cements and fillers: A review","volume":"14","author":"Kenny","year":"2003","journal-title":"J. Mater. Sci. Mater. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"17056","DOI":"10.1038\/boneres.2017.56","article-title":"Calcium phosphate cements for bone engineering and their biological properties","volume":"5","author":"Xu","year":"2017","journal-title":"Bone Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-65050-9","article-title":"3D Bioprinting of osteochondral tissue substitutes \u2013 in vitro-chondrogenesis in multi-layered mineralized constructs","volume":"10","author":"Kilian","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"12557","DOI":"10.1021\/acsami.0c00710","article-title":"A Novel Plasma-Based Bioink Stimulates Cell Proliferation and Differentiation in Bioprinted, Mineralized Constructs","volume":"12","author":"Ahlfeld","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Trombetta, R.P., Ninomiya, M.J., El-Atawneh, I.M., Knapp, E.K., Bentley, K.L.D.M., Dunman, P.M., Schwarz, E.M., Kates, S.L., and Awad, H. (2019). Calcium Phosphate Spacers for the Local Delivery of Sitafloxacin and Rifampin to Treat Orthopedic Infections: Efficacy and Proof of Concept in a Mouse Model of Single-Stage Revision of Device-Associated Osteomyelitis. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11020094"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"215","DOI":"10.2165\/00003088-198916040-00002","article-title":"Clinical Pharmacology of 5-Fluorouracil","volume":"16","author":"Diasio","year":"1989","journal-title":"Clin. Pharmacokinet."},{"key":"ref_16","unstructured":"(2020, October 19). CAMEO Chemical Datasheet, Flurouracil, Available online: https:\/\/cameochemicals.noaa.gov\/chemical\/5005."},{"key":"ref_17","unstructured":"(2020, November 10). BASF, The Chemical Company, Soluplus, Technical Information. Available online: http:\/\/www.rumapel.com.ar\/pharma_excipientes\/ficha_tecnica\/Soluplus.pdf."},{"key":"ref_18","unstructured":"BASF SE 2020 (2020, September 19). Soluplus\u2014For Better Solubility and Bioavailability. Available online: https:\/\/pharmaceutical.basf.com\/en\/Drug-Formulation\/Soluplus.html."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.carbpol.2013.04.048","article-title":"Synthesis and characterization of pullulan-mediated silver nanoparticles and its antimicrobial activities","volume":"97","author":"Kanmani","year":"2013","journal-title":"Carbohydr. Polym."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Maniruzzaman, M. (2019). 3D and 4D Printing in Biomedical Applications: Process Engineering and Additive Manufacturing, John Wiley & Sons.","DOI":"10.1002\/9783527813704"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"5011","DOI":"10.1002\/adma.201302042","article-title":"25th Anniversary Article: Engineering Hydrogels for Biofabrication","volume":"25","author":"Malda","year":"2013","journal-title":"Adv. Mater."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"100078","DOI":"10.1016\/j.mtbio.2020.100078","article-title":"Silk fibroin nanofibers: A promising ink additive for extrusion 3D bioprinting","volume":"8","author":"Sakai","year":"2020","journal-title":"Mater. Today Bio"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"116914","DOI":"10.1016\/j.carbpol.2020.116914","article-title":"Bone-derived dECM\/alginate bioink for fabricating a 3D cell-laden mesh structure for bone tissue engineering","volume":"250","author":"Lee","year":"2020","journal-title":"Carbohydr. Polym."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wu, Y., Heikal, L., Ferns, G., Ghezzi, P., Nokhodchi, A., and Maniruzzaman, M. (2019). 3D Bioprinting of Novel Biocompatible Scaffolds for Endothelial Cell Repair. Polymers, 11.","DOI":"10.3390\/polym11121924"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Pina, S., Ribeiro, V.P., Marques, C.F., Maia, F.R., Silva, T.H., Reis, R.L., and Oliveira, J. (2019). Scaffolding Strategies for Tissue Engineering and Regenerative Medicine Applications. Materials, 12.","DOI":"10.3390\/ma12111824"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1907145","DOI":"10.1002\/adfm.201907145","article-title":"Hybrid 3D Printing of Synthetic and Cell-Laden Bioinks for Shape Retaining Soft Tissue Grafts","volume":"30","author":"Torres","year":"2020","journal-title":"Adv. Funct. Mater."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kistler, S.F., and Schweizer, P.M. (1997). Liquid Film Coating: Scientific Principles and Their Technological Implications, Chapman & Hall.","DOI":"10.1007\/978-94-011-5342-3"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Hong, Y. (2016). Electrospun Fibrous Polyurethane Scaffolds in Tissue Engineering. Advances in Polyurethane Biomaterials, Woodhead Publishing.","DOI":"10.1016\/B978-0-08-100614-6.00019-6"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/jphp.12319","article-title":"An in-vitro-in-vivo taste assessment of bitter drug: Comparative electronic tongues study","volume":"67","author":"Maniruzzaman","year":"2014","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Shi, K., Tan, D.K., Nokhodchi, A., and Maniruzzaman, M. (2019). Drop-On-Powder 3D Printing of Tablets with an Anti-Cancer Drug, 5-Fluorouracil. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11040150"},{"key":"ref_31","first-page":"473","article-title":"The effects of various factors on the release rate of a poorly solubledrug (carbamazepine) from hydroxypropyl methylcellulose matrices. S.T.P","volume":"10","author":"Akbari","year":"2000","journal-title":"J. Pharma. Sci."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/11\/1077\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:31:57Z","timestamp":1760178717000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/12\/11\/1077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,11]]},"references-count":31,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["pharmaceutics12111077"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics12111077","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,11]]}}}