title: Collagen-low molecular weight hyaluronic acid semi-interpenetrating network loaded with gelatin microspheres for cell and growth factor delivery for nucleus pulposus regeneration.
abstract: Intervertebral disc (IVD) degeneration is one of the main causes of low back pain. Current surgical treatments are complex and generally do not fully restore spine mobility. Development of injectable extracellular matrix-based hydrogels offers an opportunity for minimally invasive treatment of IVD degeneration. Here we analyze a specific formulation of collagen-low molecular weight hyaluronic acid (LMW HA) semi-interpenetrating network (semi-IPN) loaded with gelatin microspheres as a potential material for tissue engineering of the inner part of the IVD, the nucleus pulposus (NP). The material displayed a gel-like behavior, it was easily injectable as demonstrated by suitable tests and did not induce cytotoxicity or inflammation. Importantly, it supported the growth and chondrogenic differentiation potential of mesenchymal stem cells (MSC) and nasal chondrocytes (NC) in vitro and in vivo. These properties of the hydrogel were successfully combined with TGF-β3 delivery by gelatin microspheres, which promoted the chondrogenic phenotype. Altogether, collagen-LMW HA loaded with gelatin microspheres represents a good candidate material for NP tissue engineering as it combines important rheological, functional and biological features.
authors: Institute of Pathology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany. Electronic address: tsaryk@uni-mainz.de.
authors: Roman
authors: R
authors: Tsaryk
authors: Institute of Polymers, Composites and Biomaterials, National Research Council of Italy, Naples, Italy.
authors: Antonio
authors: A
authors: Gloria
authors: Institute of Polymers, Composites and Biomaterials, National Research Council of Italy, Naples, Italy.
authors: Teresa
authors: T
authors: Russo
authors: Institute of Pathology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors: Laura
authors: L
authors: Anspach
authors: Institute of Polymers, Composites and Biomaterials, National Research Council of Italy, Naples, Italy.
authors: Roberto
authors: R
authors: De Santis
authors: Institute of Pathology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany; Department for Oral, Cranio-Maxillofacial and Facial Plastic Surgery, Medical Center of the Goethe University, Frankfurt, Germany.
authors: Shahram
authors: S
authors: Ghanaati
authors: Institute of Pathology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors: Ronald E
authors: RE
authors: Unger
authors: Institute of Polymers, Composites and Biomaterials, National Research Council of Italy, Naples, Italy.
authors: Luigi
authors: L
authors: Ambrosio
authors: Institute of Pathology, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
authors: C James
authors: CJ
authors: Kirkpatrick
mesh_terms: D000818:Animals; D020219:Chondrogenesis / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology*; D055119:Elastic Modulus; D005780:Gelatin / Q000494:pharmacology*; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D020007:Implants, Experimental; D007267:Injections; D007403:Intervertebral Disc / Q000502:physiology*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology; D016513:Mice, SCID; D008863:Microspheres; D008970:Molecular Weight; D012038:Regeneration / Q000187:drug effects*; D012212:Rheology / Q000187:drug effects; D053782:Transforming Growth Factor beta3 / Q000494:pharmacology*; D014783:Viscosity
chemical_list: D053782:Transforming Growth Factor beta3; D005780:Gelatin; D006820:Hyaluronic Acid; D003094:Collagen
keywords: Chondrocyte; Collagen; Hydrogel; Intervertebral disc; Mesenchymal stem cell