Injectable porous microspheres form highly porous scaffolds after injection

Injectable scaffolds are of interest in the field of regenerative medicine because of their minimally invasive mode of delivery. For tissue repair applications, it is essential that such scaffolds have the mechanical properties, porosity and pore diameter to support the formation of new tissue. In the current study, porous poly(DL-lactic acid-co-glycolic acid) (PLGA) microspheres were fabricated with an average size of 84 ± 24 lm for use as injectable cell carriers. Treatment with ethanolic sodium hydroxide for 2 min was observed to increase surface porosity without causing the microsphere structure to disintegrate. This surface treatment also enabled the microspheres to fuse together at 37 C to form scaffold structures. The average compressive strength of the scaffolds after 24 h at 37 C was 0.9 ± 0.1 MPa, and the average Young’s modulus was 9.4 ± 1.2 MPa. Scaffold porosity levels were 81.6% on average, with a mean pore diameter of 54 ± 38 lm. This study demonstrates a method for fabricating porous PLGA microspheres that form solid porous scaffolds at body temperature, creating an injectable system capable of supporting NIH-3T3 cell attachment and proliferation in vitro. 2014 Acta Materialia Inc. Published by Elsevier Ltd. This is an open access article under the CC BY-NCND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

[1]  D. Puleo,et al.  Mechanical properties and dual drug delivery application of poly(lactic-co-glycolic acid) scaffolds fabricated with a poly(β-amino ester) porogen. , 2014, Acta biomaterialia.

[2]  K. Shakesheff,et al.  Controlled release of BMP‐2 from a sintered polymer scaffold enhances bone repair in a mouse calvarial defect model , 2014, Journal of tissue engineering and regenerative medicine.

[3]  K. Shakesheff,et al.  The osteogenic response of mesenchymal stem cells to an injectable PLGA bone regeneration system. , 2013, Biomaterials.

[4]  Sung‐Wook Choi,et al.  Uniform tricalcium phosphate beads with an open porous structure for tissue engineering. , 2013, Colloids and surfaces. B, Biointerfaces.

[5]  Xiaodong Cao,et al.  Facile development of a hollow composite microsphere with porous surface for cell delivery , 2013 .

[6]  Fergal J O'Brien,et al.  Cell-scaffold interactions in the bone tissue engineering triad. , 2013, European cells & materials.

[7]  Giles T S Kirby,et al.  Accelerating protein release from microparticles for regenerative medicine applications , 2013, Materials science & engineering. C, Materials for biological applications.

[8]  Giles T S Kirby,et al.  PLGA/PEG-hydrogel composite scaffolds with controllable mechanical properties. , 2013, Journal of biomedical materials research. Part B, Applied biomaterials.

[9]  Amit Bandyopadhyay,et al.  Recent advances in bone tissue engineering scaffolds. , 2012, Trends in biotechnology.

[10]  Michel Modo,et al.  Neo-vascularization of the stroke cavity by implantation of human neural stem cells on VEGF-releasing PLGA microparticles. , 2012, Biomaterials.

[11]  K. Shakesheff,et al.  Directed differentiation of human embryonic stem cells to interrogate the cardiac gene regulatory network. , 2011, Molecular therapy : the journal of the American Society of Gene Therapy.

[12]  Giles T S Kirby,et al.  PLGA-Based Microparticles for the Sustained Release of BMP-2 , 2011 .

[13]  A. C. Jayasuriya,et al.  Evaluation of cross‐linked chitosan microparticles for bone regeneration , 2010, Journal of tissue engineering and regenerative medicine.

[14]  J. S. Park,et al.  Osteogenic differentiation of human mesenchymal stem cells using RGD-modified BMP-2 coated microspheres. , 2010, Biomaterials.

[15]  Jack Price,et al.  Attachment of stem cells to scaffold particles for intra-cerebral transplantation , 2009, Nature Protocols.

[16]  R. Guldberg,et al.  Injectable poly(lactic-co-glycolic) acid scaffolds with in situ pore formation for tissue engineering. , 2009, Acta biomaterialia.

[17]  Jack Price,et al.  The support of neural stem cells transplanted into stroke-induced brain cavities by PLGA particles. , 2009, Biomaterials.

[18]  Y. Yeo,et al.  Development of highly porous large PLGA microparticles for pulmonary drug delivery. , 2009, Biomaterials.

[19]  Byung-Soo Kim,et al.  Open Macroporous Poly(lactic-co-glycolic Acid) Microspheres as an Injectable Scaffold for Cartilage Tissue Engineering , 2009, Journal of biomaterials science. Polymer edition.

[20]  David J Mooney,et al.  Cell delivery mechanisms for tissue repair. , 2008, Cell stem cell.

[21]  Ralph Müller,et al.  Nondestructive micro-computed tomography for biological imaging and quantification of scaffold-bone interaction in vivo. , 2007, Biomaterials.

[22]  Cato T Laurencin,et al.  In vitro evaluation of chitosan/poly(lactic acid-glycolic acid) sintered microsphere scaffolds for bone tissue engineering. , 2006, Biomaterials.

[23]  H. Chung,et al.  Biodegradable polymeric microspheres with "open/closed" pores for sustained release of human growth hormone. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[24]  Jie Ren,et al.  The bone formation in vitro and mandibular defect repair using PLGA porous scaffolds. , 2005, Journal of biomedical materials research. Part A.

[25]  D. Kaplan,et al.  Porosity of 3D biomaterial scaffolds and osteogenesis. , 2005, Biomaterials.

[26]  K. Leong,et al.  The design of scaffolds for use in tissue engineering. Part I. Traditional factors. , 2001, Tissue engineering.

[27]  Y. Ikada,et al.  Accelerated tissue regeneration through incorporation of basic fibroblast growth factor-impregnated gelatin microspheres into artificial dermis. , 2000, Biomaterials.

[28]  P. Rüegsegger,et al.  Direct Three‐Dimensional Morphometric Analysis of Human Cancellous Bone: Microstructural Data from Spine, Femur, Iliac Crest, and Calcaneus , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[29]  R Langer,et al.  Surface hydrolysis of poly(glycolic acid) meshes increases the seeding density of vascular smooth muscle cells. , 1998, Journal of biomedical materials research.

[30]  S D Cook,et al.  In vivo performance of a modified CSTi dental implant coating. , 1998, The International journal of oral & maxillofacial implants.

[31]  H. Ohgushi,et al.  BMP-induced osteogenesis on the surface of hydroxyapatite with geometrically feasible and nonfeasible structures: topology of osteogenesis. , 1998, Journal of biomedical materials research.

[32]  Tabatabaei Qomi,et al.  The Design of Scaffolds for Use in Tissue Engineering , 2014 .

[33]  T. Park,et al.  Gas foamed open porous biodegradable polymeric microspheres. , 2006, Biomaterials.