845222370cb072909ad857686d802d87 pmc_11507435.pdf 65607948b07f05fef8efb626aa9ff756032b6261 pmc_11507435.pdf 3483af78f83569c55c0f5f08bb04560456ef57e128cc652e57a442a5969f64a1 pmc_11507435.pdf Title: BioMOF@cellulose Glycerogel Scaffold with Multifold Bioactivity: Perspective in Bone Tissue Repair Subject: The development of new biomaterials for musculoskeletal tissue repair is currently an important branch in biomedicine research. The approach presented here is centered around the development of a prototypic synthetic glycerogel scaffold for bone regeneration, which simultaneously features therapeutic activity. The main novelty of this work lies in the combination of an open meso and macroporous nanocrystalline cellulose (NCC)-based glycerogel with a fully biocompatible microporous bioMOF system (CaSyr-1) composed of calcium ions and syringic acid. The bioMOF framework is further impregnated with a third bioactive component, i.e., ibuprofen (ibu), to generate a multifold bioactive system. The integrated CaSyr-1(ibu) serves as a reservoir for bioactive compounds delivery, while the NCC scaffold is the proposed matrix for cell ingrowth, proliferation and differentiation. The measured drug delivery profiles, studied in a phosphate-buffered saline solution at 310 K, indicate that the bioactive components are released concurrently with bioMOF dissolution after ca. 30 min following a pseudo-first-order kinetic model. Furthermore, according to the semi-empirical Korsmeyer-Peppas kinetic model, this release is governed by a case-II mechanism, suggesting that the molecular transport is influenced by the relaxation of the NCC matrix. Preliminary in vitro results denote that the initial high concentration of glycerol in the NCC scaffold can be toxic in direct contact with human osteoblasts (HObs). However, when the excess of glycerol is diluted in the system (after the second day of the experiment), the direct and indirect assays confirm full biocompatibility and suitability for HOb proliferation. Keywords: glycerogel; cellulose; bioMOF; composite; scaffold; tissue repair Author: Albert Rosado, Alejandro Borrás, Miguel Sánchez-Soto, Magdaléna Labíková, Hubert Hettegger, Rosa Ana Ramírez-Jiménez, Luís Rojo, Luís García-Fernández, María Rosa Aguilar, Falk Liebner, Ana M. López-Periago, José A. Ayllón and Concepción Domingo Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Tue Oct 8 10:41:16 2024 CEST ModDate: Tue Oct 8 10:50:42 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 16 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 3940653 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- JYPLJJ+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 FWIIXA+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 BDICNP+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 XQKNEE+URWPalladioL-Ital Type 1 Custom yes yes yes 27 0 THNCCD+VnURWPalladioL Type 1 Custom yes yes yes 32 0 HWCLVA+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 48 0 LMEWJS+CMSY10 Type 1 Builtin yes yes yes 66 0 AOZOVO+EURM10 Type 1 Builtin yes yes yes 74 0 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IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Results and Discussion Destination: section.2 Children: Item: Title: Composite Synthesis and Composition Destination: subsection.2.1 Item: Title: Scaffold Structure and Porosity Destination: subsection.2.2 Item: Title: Mechanical Properties Destination: subsection.2.3 Item: Title: Release of Bioactive Compounds Destination: subsection.2.4 Item: Title: In Vitro Tests Destination: subsection.2.5 Item: Title: Conclusions Destination: section.3 Item: Title: Materials and Methods Destination: section.4 Children: Item: Title: Materials Destination: subsection.4.1 Item: Title: Synthetic Procedure Destination: subsection.4.2 Item: Title: Characterization Destination: subsection.4.3 Children: Item: Title: Physicochemical, Morphological, and Mechanical Properties Destination: subsubsection.4.3.1 Item: Title: Release of Bioactive Compounds Destination: subsubsection.4.3.2 Item: Title: In Vitro Tests Destination: subsubsection.4.3.3 Item: Title: References Destination: appendix.A. Info: Title: BioMOF@cellulose Glycerogel Scaffold with Multifold Bioactivity: Perspective in Bone Tissue Repair Author: Albert Rosado, Alejandro Borrás, Miguel Sánchez-Soto, Magdaléna Labíková, Hubert Hettegger, Rosa Ana Ramírez-Jiménez, Luís Rojo, Luís García-Fernández, María Rosa Aguilar, Falk Liebner, Ana M. López-Periago, José A. Ayllón and Concepción Domingo Subject: The development of new biomaterials for musculoskeletal tissue repair is currently an important branch in biomedicine research. The approach presented here is centered around the development of a prototypic synthetic glycerogel scaffold for bone regeneration, which simultaneously features therapeutic activity. The main novelty of this work lies in the combination of an open meso and macroporous nanocrystalline cellulose (NCC)-based glycerogel with a fully biocompatible microporous bioMOF system (CaSyr-1) composed of calcium ions and syringic acid. The bioMOF framework is further impregnated with a third bioactive component, i.e., ibuprofen (ibu), to generate a multifold bioactive system. The integrated CaSyr-1(ibu) serves as a reservoir for bioactive compounds delivery, while the NCC scaffold is the proposed matrix for cell ingrowth, proliferation and differentiation. The measured drug delivery profiles, studied in a phosphate-buffered saline solution at 310 K, indicate that the bioactive components are released concurrently with bioMOF dissolution after ca. 30 min following a pseudo-first-order kinetic model. Furthermore, according to the semi-empirical Korsmeyer-Peppas kinetic model, this release is governed by a case-II mechanism, suggesting that the molecular transport is influenced by the relaxation of the NCC matrix. Preliminary in vitro results denote that the initial high concentration of glycerol in the NCC scaffold can be toxic in direct contact with human osteoblasts (HObs). However, when the excess of glycerol is diluted in the system (after the second day of the experiment), the direct and indirect assays confirm full biocompatibility and suitability for HOb proliferation. 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