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Immobilization of nanocarriers within a porous chitosan scaffold for the sustained delivery of growth factors in bone tissue engineering applications.

Abstract

To guide the natural bone regeneration process, bone tissue engineering strategies rely on the development of a scaffold architecture that mimics the extracellular matrix and incorporates important extracellular signaling molecules, which promote fracture healing and bone formation pathways. Incorporation of growth factors into particles embedded within the scaffold can offer both protection of protein bioactivity and a sustained release profile. In this work, a novel method to immobilize carrier nanoparticles within scaffold pores is proposed. A biodegradable, osteoconductive, porous chitosan scaffold was fabricated via the "freeze-drying method," leading to scaffolds with a storage modulus of 8.5 kPa and 300 μm pores, in line with existing bone scaffold properties. Next, poly(methyl methacrylate-co-methacrylic acid) nanoparticles were synthesized and immobilized to the scaffold via carbodiimide-crosslinker chemistry. A fluorescent imaging study confirmed that the conventional methods of protein and nanocarrier incorporation into scaffolds can lead to over 60% diffusion out of the scaffold within the first 5 min of implantation, and total disappearance within 4 weeks. The novel method of nanocarrier immobilization to the scaffold backbone via carbodiimide-crosslinker chemistry allows full retention of particles for up to 4 weeks within the scaffold bulk, with no negative effects on the viability and proliferation of human umbilical vein endothelial cells.

Authors+Show Affiliations

Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas. Department of Biomechanical Engineering, Delft University of Technology (TU Delft), Delft, Netherlands.McKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas. Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, Austin, Texas.Department of Biomechanical Engineering, Delft University of Technology (TU Delft), Delft, Netherlands.Department of Biomechanical Engineering, Delft University of Technology (TU Delft), Delft, Netherlands.Department of Biomedical Engineering, The University of Texas at Austin, Austin, Texas. McKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas. Institute for Biomaterials, Drug Delivery, and Regenerative Medicine, The University of Texas at Austin, Austin, Texas. Department of Pediatrics, and Department of Surgery and Perioperative Care, Dell Medical School, The University of Texas at Austin, Austin, Texas. Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, Texas.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31971334

Citation

De Witte, Tinke-Marie, et al. "Immobilization of Nanocarriers Within a Porous Chitosan Scaffold for the Sustained Delivery of Growth Factors in Bone Tissue Engineering Applications." Journal of Biomedical Materials Research. Part A, 2020.
De Witte TM, Wagner AM, Fratila-Apachitei LE, et al. Immobilization of nanocarriers within a porous chitosan scaffold for the sustained delivery of growth factors in bone tissue engineering applications. J Biomed Mater Res A. 2020.
De Witte, T. M., Wagner, A. M., Fratila-Apachitei, L. E., Zadpoor, A. A., & Peppas, N. A. (2020). Immobilization of nanocarriers within a porous chitosan scaffold for the sustained delivery of growth factors in bone tissue engineering applications. Journal of Biomedical Materials Research. Part A, doi:10.1002/jbm.a.36887.
De Witte TM, et al. Immobilization of Nanocarriers Within a Porous Chitosan Scaffold for the Sustained Delivery of Growth Factors in Bone Tissue Engineering Applications. J Biomed Mater Res A. 2020 Jan 23; PubMed PMID: 31971334.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immobilization of nanocarriers within a porous chitosan scaffold for the sustained delivery of growth factors in bone tissue engineering applications. AU - De Witte,Tinke-Marie, AU - Wagner,Angela M, AU - Fratila-Apachitei,Lidy E, AU - Zadpoor,Amir A, AU - Peppas,Nicholas A, Y1 - 2020/01/23/ PY - 2019/10/14/received PY - 2020/01/20/accepted PY - 2020/1/24/pubmed PY - 2020/1/24/medline PY - 2020/1/24/entrez KW - 3D porous scaffold KW - bone regeneration KW - chitosan scaffold KW - growth factor delivery KW - sustained release JF - Journal of biomedical materials research. Part A JO - J Biomed Mater Res A N2 - To guide the natural bone regeneration process, bone tissue engineering strategies rely on the development of a scaffold architecture that mimics the extracellular matrix and incorporates important extracellular signaling molecules, which promote fracture healing and bone formation pathways. Incorporation of growth factors into particles embedded within the scaffold can offer both protection of protein bioactivity and a sustained release profile. In this work, a novel method to immobilize carrier nanoparticles within scaffold pores is proposed. A biodegradable, osteoconductive, porous chitosan scaffold was fabricated via the "freeze-drying method," leading to scaffolds with a storage modulus of 8.5 kPa and 300 μm pores, in line with existing bone scaffold properties. Next, poly(methyl methacrylate-co-methacrylic acid) nanoparticles were synthesized and immobilized to the scaffold via carbodiimide-crosslinker chemistry. A fluorescent imaging study confirmed that the conventional methods of protein and nanocarrier incorporation into scaffolds can lead to over 60% diffusion out of the scaffold within the first 5 min of implantation, and total disappearance within 4 weeks. The novel method of nanocarrier immobilization to the scaffold backbone via carbodiimide-crosslinker chemistry allows full retention of particles for up to 4 weeks within the scaffold bulk, with no negative effects on the viability and proliferation of human umbilical vein endothelial cells. SN - 1552-4965 UR - https://www.unboundmedicine.com/medline/citation/31971334/Immobilization_of_Nanocarriers_within_a_Porous_Chitosan_Scaffold_for_the_Sustained_Delivery_of_Growth_Factors_in_Bone_Tissue_Engineering_Applications L2 - https://doi.org/10.1002/jbm.a.36887 DB - PRIME DP - Unbound Medicine ER -