Injectable biodegradable polycaprolactone-sebacic acid gels for bone tissue engineering.

Tissue engineering constitutes a promising alternative technology to transplantation medicine by creating viable substitutes for failing tissues or organs. The ability to manipulate and reconstitute tissue function has tremendous clinical implications and will most likely play a key role in cell and gene therapies in the coming years. In the present work, a novel injectable and biodegradable biomaterial is reported that could be injected on the human body with a surgical syringe. The material prepared is a blend of polycaprolactone (PCL), a biodegradable and elastic biomedical polymer, and sebacic acid, a natural polymer part of castor oil with low molecular weight to accelerate the slow degradation rate of PCL. The biocompatibility of the blend was evaluated in vitro and its in vivo behavior was also assessed through subcutaneous and bone implantation in rats to evaluate its tissue-forming ability and degradation rate. The results allowed the conclusion that the gel is biocompatible, promotes the differentiation of mesenchymal stem cells, and presents an adequate degradation rate for use in bone tissue engineering. In vivo the gel blends promoted tissue regeneration and adverse reactions were not observed on subcutaneous and bone implants.

[1]  B. Ratner.  The blood compatibility catastrophe. , 1993, Journal of biomedical materials research.

[2]  D W Hutmacher,et al.  The stimulation of healing within a rat calvarial defect by mPCL-TCP/collagen scaffolds loaded with rhBMP-2. , 2009, Biomaterials.

[3]  Pedro L Granja,et al.  Molecularly designed alginate hydrogels susceptible to local proteolysis as three-dimensional cellular microenvironments. , 2011, Acta biomaterialia.

[4]  R. Reis,et al.  Bioinert, biodegradable and injectable polymeric matrix composites for hard tissue replacement: state of the art and recent developments , 2004 .

[5]  T. Hefferan,et al.  Synthesis, material properties, and biocompatibility of a novel self-cross-linkable poly(caprolactone fumarate) as an injectable tissue engineering scaffold. , 2005, Biomacromolecules.

[6]  M. Harmsen,et al.  Cellular and molecular dynamics in the foreign body reaction. , 2006, Tissue engineering.

[7]  Dietmar W. Hutmacher,et al.  Biodegradable polymers applied in tissue engineering research: a review , 2007 .

[8]  M. Lamghari,et al.  Proliferation, activity, and osteogenic differentiation of bone marrow stromal cells cultured on calcium titanium phosphate microspheres. , 2005, Journal of biomedical materials research. Part A.

[9]  Toshihiro Akaike,et al.  A novel degradable polycaprolactone networks for tissue engineering. , 2003, Biomaterials.

[10]  Antonios G Mikos,et al.  Development of an injectable, in situ crosslinkable, degradable polymeric carrier for osteogenic cell populations. Part 2. Viability of encapsulated marrow stromal osteoblasts cultured on crosslinking poly(propylene fumarate). , 2002, Biomaterials.

[11]  C. Zavaglia,et al.  Porous and dense poly(L-lactic acid) and poly(D,L-lactic acid-co-glycolic acid) scaffolds: In vitro degradation in culture medium and osteoblasts culture , 2004, Journal of materials science. Materials in medicine.

[12]  Antonios G Mikos,et al.  Development of an injectable, in situ crosslinkable, degradable polymeric carrier for osteogenic cell populations. Part 1. Encapsulation of marrow stromal osteoblasts in surface crosslinked gelatin microparticles. , 2002, Biomaterials.

[13]  R. Bareille,et al.  The effect of the co-immobilization of human osteoprogenitors and endothelial cells within alginate microspheres on mineralization in a bone defect. , 2009, Biomaterials.

[14]  Rui L Reis,et al.  Bone tissue engineering: state of the art and future trends. , 2004, Macromolecular bioscience.

[15]  Bruck Sd,et al.  New ideas in biomaterials science--a path to engineered biomaterials. , 1994 .

[16]  Colleen L Flanagan,et al.  Bone tissue engineering using polycaprolactone scaffolds fabricated via selective laser sintering. , 2005, Biomaterials.

[17]  A. Albertsson,et al.  Controlled degradation by artificial and biological processes , 1996 .

[18]  B. Sykes,et al.  Characterization of cells with high alkaline phosphatase activity derived from human bone and marrow: preliminary assessment of their osteogenicity. , 1985, Bone.

[19]  S. M. Li,et al.  Bioresorbability and biocompatibility of aliphatic polyesters , 1992 .

[20]  F. Munarin,et al.  Pectin-based injectable biomaterials for bone tissue engineering. , 2011, Biomacromolecules.

[21]  C. Zavaglia,et al.  Synthesis and characterization of poly(L-lactic acid) membranes: Studies in vivo and in vitro , 2003, Journal of materials science. Materials in medicine.

[22]  D. Hutmacher,et al.  The return of a forgotten polymer : Polycaprolactone in the 21st century , 2009 .

[23]  R. Gross,et al.  Hydrolytic degradation of PCL/PEO copolymers in alkaline media , 2000, Journal of materials science. Materials in medicine.

[24]  Antonios G Mikos,et al.  Injectable matrices and scaffolds for drug delivery in tissue engineering. , 2007, Advanced drug delivery reviews.

[25]  M. Lamghari,et al.  Biological evaluation of calcium alginate microspheres as a vehicle for the localized delivery of a therapeutic enzyme. , 2005, Journal of biomedical materials research. Part A.

[26]  Swee Hin Teoh,et al.  Evaluation of polycaprolactone scaffold degradation for 6 months in vitro and in vivo. , 2009, Journal of biomedical materials research. Part A.

[27]  C. Chu.  Biodegradable Polymeric Biomaterials: An Updated Overview , 2007 .

[28]  James M. Anderson,et al.  Quantitative in vivo cytokine analysis at synthetic biomaterial implant sites. , 2008, Journal of biomedical materials research. Part A.

[29]  K. Ghosh,et al.  Tissue engineering for cutaneous wounds. , 2007, The Journal of investigative dermatology.

[30]  M. Sefton,et al.  Viability and protein secretion from human Hepatoma (HepG2) cells encapsulated in 400‐μm polyacrylate microcapsules by submerged nozzle–liquid jet extrusion , 1994, Biotechnology and bioengineering.

[31]  J. Polak,et al.  Bioactive materials to control cell cycle , 2000 .

[32]  L. Ambrosio,et al.  Human bone marrow stromal cells: In vitro expansion and differentiation for bone engineering. , 2006, Biomaterials.

[33]  David J Mooney,et al.  Upregulation of bone cell differentiation through immobilization within a synthetic extracellular matrix. , 2007, Biomaterials.

[34]  Buddy D. Ratner,et al.  Biomaterials Science: An Introduction to Materials in Medicine , 1996 .

[35]  R. Soares,et al.  Immobilization of human mesenchymal stem cells within RGD-grafted alginate microspheres and assessment of their angiogenic potential. , 2010, Biomacromolecules.

[36]  A. Domb,et al.  Poly(sebacic acid-co-ricinoleic acid) biodegradable carrier for paclitaxel: in vitro release and in vivo toxicity. , 2004, Journal of biomedical materials research. Part A.

[37]  Jacqueline A. Jones,et al.  Lymphocyte/macrophage interactions: biomaterial surface-dependent cytokine, chemokine, and matrix protein production. , 2008, Journal of biomedical materials research. Part A.

[38]  A. Domb,et al.  Copolymers of pharmaceutical grade lactic acid and sebacic acid: drug release behavior and biocompatibility. , 2006, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[39]  P. Bongrand,et al.  Is there a predictable relationship between surface physical-chemical properties and cell behaviour at the interface? , 2004, European cells & materials.

[40]  S C Woodward,et al.  The intracellular degradation of poly(epsilon-caprolactone). , 1985, Journal of biomedical materials research.

[41]  F. Moatamed,et al.  The intracellular degradation of poly(ε-caprolactone) , 1985 .