{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:52:36Z","timestamp":1790790756659,"version":"4.1.0"},"reference-count":81,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Republic of Kazakhstan","award":["AP26197781"],"award-info":[{"award-number":["AP26197781"]}]},{"award":["AP26197781"],"award-info":[{"award-number":["AP26197781"]}],"id":[{"id":"https:\/\/ror.org\/05tyne317","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: The development of multifunctional biomaterials for bone regeneration remains a key challenge in additive manufacturing. Although polylactic acid (PLA) is widely used in fused deposition modeling (FDM), its limited bioactivity and lack of intrinsic antibacterial functionality restrict its application in implantable constructs. This study aimed to develop a PLA-based composite filament combining ion-mediated bioactive potential and local antibacterial functionality using a Quality by Design (QbD) approach. Methods: PLA-based composite filaments incorporating a mollusk shell-derived biogenic calcium-containing filler (20 wt.%) and gentamicin (5 wt.%) were fabricated by solvent-free melt extrusion. A QbD framework was applied to define the Quality Target Product Profile (QTPP), identify critical quality attributes (CQAs), and assess critical material attributes (CMAs) and critical process parameters (CPPs). The material was characterized by SEM\u2013EDS combined with ImageJ-based quantitative image analysis, TGA\/DSC, mechanical testing, ICP-AES analysis of aqueous extracts, agar diffusion antibacterial assays, FDM printability assessment, and in vivo biocompatibility testing in a rat subcutaneous implantation model. Results: The developed PLA\u2013Gen\u2013MS material was obtained as a continuous filament with a diameter of 1.75 \u00b1 0.05 mm and was successfully used for FDM printing of model scaffold structures. SEM\u2013EDS confirmed matrix continuity and distribution of the calcium-containing mineral phase. ICP-AES revealed a calcium-dominant multicomponent ion release profile, with Ca as the predominant element and measurable levels of Sr, Mg, P, Mn, and Fe. TGA\/DSC confirmed thermal compatibility of the components under melt-processing conditions. PLA\u2013Gen\u2013MS demonstrated antibacterial activity against all tested strains, with inhibition zones of approximately 20\u201321 mm. In vivo, the material showed a favorable preliminary tissue response compared with TiLOOP\u00ae, including faster reduction of inflammatory infiltration and absence of foreign body giant cells by day 14. Conclusions: The QbD-guided strategy enabled the development of a multifunctional PLA-based filament integrating melt processability, structural integrity, ion-mediated bioactive potential, antibacterial functionality, printability, and favorable preliminary biocompatibility. PLA\u2013Gen\u2013MS can be considered a promising platform for further development of personalized bioactive and antibacterial scaffold constructs for bone regeneration.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091055","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T15:01:07Z","timestamp":1787670067000},"page":"1055","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Bioactive PLA Filament with Antibacterial and Ion-Releasing Properties for Additive Manufacturing of Bone Scaffolds: QbD-Guided Development"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2214-0165","authenticated-orcid":false,"given":"Anastassiya","family":"Khrustaleva","sequence":"first","affiliation":[{"name":"School of Pharmacy, Karaganda Medical University, 100008 Karaganda, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3047-8200","authenticated-orcid":false,"given":"Azamat","family":"Yedrissov","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Karaganda Medical University, 100008 Karaganda, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitriy","family":"Khrustalev","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Karaganda Medical University, 100008 Karaganda, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Chernykh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ryazan State Medical University, 390026 Ryazan, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9302-499X","authenticated-orcid":false,"given":"Aleksandr","family":"Samorodov","sequence":"additional","affiliation":[{"name":"Translational Research Laboratory, All-Russian Scientific Research Institute of Medicinal and Aromatic Plants, 117216 Moscow, Russia"},{"name":"Department of Pharmacology, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saule","family":"Akhmetova","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Karaganda Medical University, 100008 Karaganda, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2472-8235","authenticated-orcid":false,"given":"Artyom","family":"Savelyev","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Karaganda Medical University, 100008 Karaganda, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1869-859X","authenticated-orcid":false,"given":"Marlen","family":"Kiikbayev","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Karaganda Medical University, 100008 Karaganda, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8379-5012","authenticated-orcid":false,"given":"Polina","family":"Rusyaeva","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Karaganda Medical University, 100008 Karaganda, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6198-3167","authenticated-orcid":false,"given":"Vladimir","family":"Kazantsev","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Karaganda Medical University, 100008 Karaganda, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6694-1608","authenticated-orcid":false,"given":"Kristina","family":"Perepelitsyna","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Karaganda Medical University, 100008 Karaganda, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0063-0746","authenticated-orcid":false,"given":"Sofiya","family":"Shapovalenko","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Karaganda Medical University, 100008 Karaganda, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2026, April 05). 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