Tailoring the delivery of therapeutic ions from bioactive scaffolds while inhibiting their apatite nucleation: a coaxial electrospinning strategy for soft tissue regeneration

The delivery of therapeutic ions, as a key element for the regeneration of soft tissue, represents a viable alternative to conventional drugs. Primarily designed for the regeneration of hard tissue, degradable bioactive inorganic matrices are a carrier of choice for the delivery of ionic chemical cues. However, they nucleate calcium-phosphate crystal on their surface, which could be undesired for most soft tissue regeneration. Here, a coaxial electrospinning process was engineered, generating core–shell fibres with inorganic particles enclosed within a bio-inert polymeric shell. Silicon doped vaterite (SiV) dispersed in poly(L-lactic acid) was selected as an inorganic composite core and poly(D,L-lactide-co-glycolide) (PLGA) as a shell. By careful selection of the electrospinning parameters, fibres of constant diameter (≈10 μm) with controllable shell thickness (from 1.3 to 4.2 μm) were obtained. The release of calcium and silica followed the Weibull model, showing a purely diffusive release after hydration of the PLGA layer. The rate of release could be controlled with the shell thickness. The nucleation of calcium-phosphate crystals was inhibited. In addition, with the presence of a PLGA shell layer, the mechanical properties of the fibermats were greatly improved with, for instance, an increase of the Young's modulus up to 536% as compared to original composite. These non-woven porous materials are an affordable investigation platform to study the effect of local ionic release onto the surrounding cell metabolism.

[1]  Julian R. Jones,et al.  Lithium-silicate sol–gel bioactive glass and the effect of lithium precursor on structure–property relationships , 2016, Journal of Sol-Gel Science and Technology.

[2]  Julian R. Jones,et al.  Preparation of Cotton-Wool-Like Poly(lactic acid)-Based Composites Consisting of Core-Shell-Type Fibers , 2015, Materials.

[3]  G. G. Peters,et al.  Electrospinning poly(ε-caprolactone) under controlled environmental conditions: Influence on fiber morphology and orientation , 2015 .

[4]  Aldo R Boccaccini,et al.  Bioactive glasses beyond bone and teeth: emerging applications in contact with soft tissues. , 2015, Acta biomaterialia.

[5]  Y. Sakka,et al.  Preparation of siloxane-containing vaterite doped with magnesium , 2014 .

[6]  M. Stevens,et al.  Cotton-wool-like bioactive glasses for bone regeneration. , 2014, Acta biomaterialia.

[7]  A. Obata,et al.  Preparation of electrospun fiber mats using siloxane-containing vaterite and biodegradable polymer hybrids for bone regeneration. , 2013, Journal of biomedical materials research. Part B, Applied biomaterials.

[8]  T. Kasuga,et al.  Preparation of siloxane-containing vaterite particles with red-blood-cell-like morphologies and incorporation of calcium-salt polylactide for bone regenerative medicine , 2013 .

[9]  Julian R. Jones,et al.  Tracking the formation of vaterite particles containing aminopropyl-functionalized silsesquioxane and their structure for bone regenerative medicine. , 2013, Journal of materials chemistry. B.

[10]  J. Cordeiro,et al.  The role of transcription-independent damage signals in the initiation of epithelial wound healing , 2013, Nature Reviews Molecular Cell Biology.

[11]  Wang Lu,et al.  Core-shell Fibers for Biomedical Applications-A Review , 2013 .

[12]  A. Huttenlocher,et al.  Early redox, Src family kinase, and calcium signaling integrate wound responses and tissue regeneration in zebrafish , 2012, The Journal of cell biology.

[13]  A. Obata,et al.  Effects of niobium ions released from calcium phosphate invert glasses containing Nb2O5 on osteoblast-like cell functions. , 2012, ACS applied materials & interfaces.

[14]  S. Wong,et al.  Fabrication of PVDF/PVA microtubules by coaxial electrospinning , 2012 .

[15]  M. Szczepanski,et al.  The mechanism of vascular calcification – a systematic review , 2012, Medical science monitor : international medical journal of experimental and clinical research.

[16]  Seetha S Manickam,et al.  Controlling electrospun nanofiber morphology and mechanical properties using humidity , 2011 .

[17]  M. Longaker,et al.  Calcium-Based Nanoparticles Accelerate Skin Wound Healing , 2011, PloS one.

[18]  Hirenkumar K. Makadia,et al.  Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier. , 2011, Polymers.

[19]  Delbert E Day,et al.  Bioactive glass in tissue engineering. , 2011, Acta biomaterialia.

[20]  Aldo R Boccaccini,et al.  A review of the biological response to ionic dissolution products from bioactive glasses and glass-ceramics. , 2011, Biomaterials.

[21]  A. Obata,et al.  Effect of preparation route on the degradation behavior and ion releasability of siloxane-poly(lactic acid)-vaterite hybrid nonwoven fabrics for guided bone regeneration. , 2011, Dental materials journal.

[22]  Julian R. Jones,et al.  Preparation of electrospun siloxane-poly(lactic acid)-vaterite hybrid fibrous membranes for guided bone regeneration , 2010 .

[23]  S. Ghazizadeh,et al.  Protein Kinase D Is Implicated in the Reversible Commitment to Differentiation in Primary Cultures of Mouse Keratinocytes* , 2010, The Journal of Biological Chemistry.

[24]  A. Obata,et al.  Electrospun microfiber meshes of silicon-doped vaterite/poly(lactic acid) hybrid for guided bone regeneration. , 2010, Acta biomaterialia.

[25]  Hani E Naguib,et al.  A study on the effect of degradation media on the physical and mechanical properties of porous PLGA 85/15 scaffolds. , 2009, Journal of biomedical materials research. Part B, Applied biomaterials.

[26]  M. Bohner,et al.  Can bioactivity be tested in vitro with SBF solution? , 2009, Biomaterials.

[27]  J. Boateng,et al.  Wound healing dressings and drug delivery systems: a review. , 2008, Journal of pharmaceutical sciences.

[28]  Bhupender S. Gupta,et al.  Co‐axial Electrospinning for Nanofiber Structures: Preparation and Applications , 2008 .

[29]  A. R. Boccaccini,et al.  Mechanical properties and bioactivity of porous PLGA/TiO2 nanoparticle-filled composites for tissue engineering scaffolds , 2007 .

[30]  Suwan N Jayasinghe,et al.  Cell electrospinning: a unique biotechnique for encapsulating living organisms for generating active biological microthreads/scaffolds. , 2006, Biomacromolecules.

[31]  Tadashi Kokubo,et al.  How useful is SBF in predicting in vivo bone bioactivity? , 2006, Biomaterials.

[32]  S. Ramakrishna,et al.  Coaxial electrospinning of (fluorescein isothiocyanate-conjugated bovine serum albumin)-encapsulated poly(epsilon-caprolactone) nanofibers for sustained release. , 2006, Biomacromolecules.

[33]  K. Kosmidis,et al.  On the use of the Weibull function for the discernment of drug release mechanisms. , 2006, International journal of pharmaceutics.

[34]  D. Kaplan,et al.  Production of Submicron Diameter Silk Fibers under Benign Processing Conditions by Two-Fluid Electrospinning , 2006 .

[35]  Ahmed El-Ghannam,et al.  Bone reconstruction: from bioceramics to tissue engineering , 2005, Expert review of medical devices.

[36]  G. Rutledge,et al.  Production of Submicrometer Diameter Fibers by Two‐Fluid Electrospinning , 2004 .

[37]  Panos Macheras,et al.  Fractal kinetics in drug release from finite fractal matrices , 2003 .

[38]  Ayako Oyane,et al.  Preparation and assessment of revised simulated body fluids. , 2003, Journal of biomedical materials research. Part A.

[39]  D. Bikle,et al.  Calcium- and vitamin D-regulated keratinocyte differentiation , 2001, Molecular and Cellular Endocrinology.

[40]  T. Nakamura,et al.  Evaluation of a novel alginate gel dressing: cytotoxicity to fibroblasts in vitro and foreign-body reaction in pig skin in vivo. , 1998, Journal of biomedical materials research.

[41]  T. Roth,et al.  Effects of calcium alginate on cellular wound healing processes modeled in vitro. , 1996, Journal of biomedical materials research.

[42]  David L Kaplan,et al.  Poly(lactic-co-glycolic) acid-controlled-release systems: experimental and modeling insights. , 2013, Critical reviews in therapeutic drug carrier systems.

[43]  Julian R Jones,et al.  Review of bioactive glass: from Hench to hybrids. , 2013, Acta biomaterialia.

[44]  A. Obata,et al.  Enhanced in vitro cell activity on silicon-doped vaterite/poly(lactic acid) composites. , 2009, Acta biomaterialia.

[45]  L. Perioli,et al.  Physicochemical characterization and release mechanism of a novel prednisone biodegradable microsphere formulation. , 2008, Journal of pharmaceutical sciences.

[46]  T. Kasuga Bioactive calcium pyrophosphate glasses and glass-ceramics. , 2005, Acta biomaterialia.

[47]  J. Deitzel,et al.  The effect of processing variables on the morphology of electrospun nanofibers and textiles , 2001 .