PMID- 36671479 OWN - NLM STAT- MEDLINE DCOM- 20230124 LR - 20230214 IS - 2218-273X (Electronic) IS - 2218-273X (Linking) VI - 13 IP - 1 DP - 2023 Jan 2 TI - Optimization of an Injectable, Resorbable, Bioactive Cement Able to Release the Anti-Osteoclastogenic Biomolecule ICOS-Fc for the Treatment of Osteoporotic Vertebral Compression Fractures. LID - 10.3390/biom13010094 [doi] LID - 94 AB - Vertebral compression fractures are typical of osteoporosis and their treatment can require the injection of a cement through a minimally invasive procedure to restore vertebral body height. This study reports the development of an injectable calcium sulphate-based composite cement able to stimulate bone regeneration while inhibiting osteoclast bone resorption. To this aim, different types of strontium-containing mesoporous glass particles (Sr-MBG) were added to calcium sulphate powder to impart a pro-osteogenic effect, and the influence of their size and textural features on the cement properties was investigated. Anti-osteoclastogenic properties were conferred by incorporating into poly(lactic-co-glycolic)acid (PLGA) nanoparticles, a recombinant protein able to inhibit osteoclast activity (i.e., ICOS-Fc). Radiopaque zirconia nanoparticles (ZrO(2)) were also added to the formulation to visualize the cement injection under fluoroscopy. The measured cement setting times were suitable for the clinical practice, and static mechanical testing determined a compressive strength of ca. 8 MPa, comparable to that of human vertebral bodies. In vitro release experiments indicated a sustained release of ICOS-Fc and Sr(2+) ions up to 28 days. Overall, the developed cement is promising for the treatment of vertebral compression fractures and has the potential to stimulate bone regeneration while releasing a biomolecule able to limit bone resorption. FAU - Banche-Niclot, Federica AU - Banche-Niclot F AUID- ORCID: 0000-0002-5855-4490 AD - Department of Applied Science and Technology, Politecnico di Torino, Corso Duca Degli Abruzzi 24, 10129 Torino, Italy. FAU - Corvaglia, Ilaria AU - Corvaglia I AD - Department of Applied Science and Technology, Politecnico di Torino, Corso Duca Degli Abruzzi 24, 10129 Torino, Italy. FAU - Cavalera, Caterina AU - Cavalera C AD - Department of Applied Science and Technology, Politecnico di Torino, Corso Duca Degli Abruzzi 24, 10129 Torino, Italy. FAU - Boggio, Elena AU - Boggio E AUID- ORCID: 0000-0003-2700-3597 AD - NOVAICOS s.r.l.s., Via Amico Canobio 4/6, 28100 Novara, Italy. AD - Department of Health Sciences, Universita del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy. FAU - Gigliotti, Casimiro Luca AU - Gigliotti CL AUID- ORCID: 0000-0002-3127-5686 AD - NOVAICOS s.r.l.s., Via Amico Canobio 4/6, 28100 Novara, Italy. AD - Department of Health Sciences, Universita del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy. FAU - Dianzani, Umberto AU - Dianzani U AD - Department of Health Sciences, Universita del Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy. FAU - Tzagiollari, Antzela AU - Tzagiollari A AUID- ORCID: 0000-0001-6157-6378 AD - Centre for Medical Engineering Research, School of Mechanical and Manufacturing Engineering, Dublin City University, D09 NA55 Dublin, Ireland. AD - Biodesign Europe, Dublin City University, D09 NA55 Dublin, Ireland. FAU - Dunne, Nicholas AU - Dunne N AUID- ORCID: 0000-0003-4649-2410 AD - Centre for Medical Engineering Research, School of Mechanical and Manufacturing Engineering, Dublin City University, D09 NA55 Dublin, Ireland. AD - Biodesign Europe, Dublin City University, D09 NA55 Dublin, Ireland. FAU - Manca, Antonio AU - Manca A AUID- ORCID: 0000-0002-8193-5208 AD - Department of Radiology, Candiolo Cancer Institute, FPO-IRCCS, 10060 Torino, Italy. FAU - Fiorilli, Sonia AU - Fiorilli S AD - Department of Applied Science and Technology, Politecnico di Torino, Corso Duca Degli Abruzzi 24, 10129 Torino, Italy. AD - National Interuniversity Consortium of Materials Science and Technology, RU Politecnico di Torino, 50121 Firenze, Italy. FAU - Vitale-Brovarone, Chiara AU - Vitale-Brovarone C AD - Department of Applied Science and Technology, Politecnico di Torino, Corso Duca Degli Abruzzi 24, 10129 Torino, Italy. AD - National Interuniversity Consortium of Materials Science and Technology, RU Politecnico di Torino, 50121 Firenze, Italy. LA - eng GR - 814410/European Union's Horizon 2020 research and innovation program/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230102 PL - Switzerland TA - Biomolecules JT - Biomolecules JID - 101596414 RN - WAT0DDB505 (Calcium Sulfate) RN - 0 (Bone Cements) RN - 0 (ICOS protein, human) RN - 0 (Inducible T-Cell Co-Stimulator Protein) SB - IM MH - Humans MH - *Fractures, Compression/drug therapy MH - *Spinal Fractures/drug therapy MH - Calcium Sulfate MH - Bone Cements/pharmacology/therapeutic use MH - *Bone Resorption MH - Inducible T-Cell Co-Stimulator Protein PMC - PMC9855932 OTO - NOTNLM OT - ICOS-Fc OT - PLGA nanoparticles OT - bone OT - calcium sulphate OT - injectable cement OT - mesoporous bioactive glasses OT - osteoporosis OT - tissue regeneration COIS- Authors Elena Boggio and Casimiro Luca Gigliotti are, respectively CTO and CEO of the company NOVAICOS s.r.l.s. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/01/22 06:00 MHDA- 2023/01/25 06:00 PMCR- 2023/01/02 CRDT- 2023/01/21 01:07 PHST- 2022/10/31 00:00 [received] PHST- 2022/12/22 00:00 [revised] PHST- 2022/12/26 00:00 [accepted] PHST- 2023/01/21 01:07 [entrez] PHST- 2023/01/22 06:00 [pubmed] PHST- 2023/01/25 06:00 [medline] PHST- 2023/01/02 00:00 [pmc-release] AID - biom13010094 [pii] AID - biomolecules-13-00094 [pii] AID - 10.3390/biom13010094 [doi] PST - epublish SO - Biomolecules. 2023 Jan 2;13(1):94. doi: 10.3390/biom13010094.