TY - JOUR

T1 - 3D-Printed composite scaffolds based on poly(ε-caprolactone) filled with poly(glutamic acid)-modified cellulose nanocrystals for improved bone tissue regeneration

AU - Averianov, Ilia

AU - Stepanova, Mariia

AU - Solomakha, Olga

AU - Gofman, Iosif

AU - Serdobintsev, Mikhail

AU - Blum, Natalya

AU - Kaftuirev, Aleksander

AU - Baulin, Ivan

AU - Nashchekina, Juliya

AU - Lavrentieva, Antonina

AU - Vinogradova, Tatiana

AU - Korzhikov-Vlakh, Viktor

AU - Korzhikova-Vlakh, Evgenia

N1 - Funding Information: The Interdisciplinary Resource Center for Nanotechnology and Centre for X-ray Diffraction Studies of Research Park of St. Petersburg State University are acknowledged for SEM and EDX analysis, and micro-CT, respectively. The authors are very grateful to Mr. Vladimir Kalganov and Mr. Alexander Kulkov for their kind help in processing of SEM/EDX and micro-CT data, respectively. Mr. Ilia Averianov thanks G-RISC program for one-month scholarship supporting his work in Institute of Technical Chemistry, Leibniz University of Hannover (project #M-2019b-6_d).

PY - 2022/9/16

Y1 - 2022/9/16

N2 - The manufacturing of modern scaffolds with customized geometry and personalization has become possible due to the three-dimensional (3D) printing technique. A novel type of 3D-printed scaffolds for bone tissue regeneration based on poly(ε-caprolactone) (PCL) filled with nanocrystalline cellulose modified by poly(glutamic acid) (PGlu-NCC) has been proposed in this study. The 3D printing set-ups were optimized in order to obtain homogeneous porous scaffolds. Both polymer composites and manufactured 3D scaffolds have demonstrated mechanical properties suitable for a human trabecular bone. Compression moduli were in the range of 334–396 MPa for non-porous PCL and PCL-based composites, and 101–122 MPa for porous scaffolds made of the same materials. In vitro mineralization study with the use of human mesenchymal stem cells (hMSCs) revealed the larger Ca deposits on the surface of PCL/PGlu-NCC composite scaffolds. Implantation of the developed 3D scaffolds into femur of the rabbits was carried out to observe close and delayed effects. The histological analysis showed the lowest content of immune cells and thin fibrous capsule, revealing low toxicity of the PCL/PGlu-NCC scaffolds seeded with rabbit MSCs (rMSCs) to the surrounding tissues. The most pronounced result on the generation of new bone tissue after implantation of PCL/PGlu-NCC + rMSCs scaffolds was detected by both microcomputed tomography and histological analysis. Around 33% and 55% of bone coverage were detected for composite 3D scaffolds with adhered rMSCs after 1 and 3 months of implantation, respectively. This achievement can be a result of synergistic effect of PGlu, which attracts calcium ions, and stem cells with osteogenic potential.

AB - The manufacturing of modern scaffolds with customized geometry and personalization has become possible due to the three-dimensional (3D) printing technique. A novel type of 3D-printed scaffolds for bone tissue regeneration based on poly(ε-caprolactone) (PCL) filled with nanocrystalline cellulose modified by poly(glutamic acid) (PGlu-NCC) has been proposed in this study. The 3D printing set-ups were optimized in order to obtain homogeneous porous scaffolds. Both polymer composites and manufactured 3D scaffolds have demonstrated mechanical properties suitable for a human trabecular bone. Compression moduli were in the range of 334–396 MPa for non-porous PCL and PCL-based composites, and 101–122 MPa for porous scaffolds made of the same materials. In vitro mineralization study with the use of human mesenchymal stem cells (hMSCs) revealed the larger Ca deposits on the surface of PCL/PGlu-NCC composite scaffolds. Implantation of the developed 3D scaffolds into femur of the rabbits was carried out to observe close and delayed effects. The histological analysis showed the lowest content of immune cells and thin fibrous capsule, revealing low toxicity of the PCL/PGlu-NCC scaffolds seeded with rabbit MSCs (rMSCs) to the surrounding tissues. The most pronounced result on the generation of new bone tissue after implantation of PCL/PGlu-NCC + rMSCs scaffolds was detected by both microcomputed tomography and histological analysis. Around 33% and 55% of bone coverage were detected for composite 3D scaffolds with adhered rMSCs after 1 and 3 months of implantation, respectively. This achievement can be a result of synergistic effect of PGlu, which attracts calcium ions, and stem cells with osteogenic potential.

KW - 3D printing

KW - biodegradable composites

KW - bone defects

KW - bone regeneration

KW - cellulose nanocrystals

KW - mesenchymal stem cells

KW - poly(glutamic acid)

KW - poly(ε-caprolactone)

KW - scaffolds

UR - http://www.scopus.com/inward/record.url?scp=85130600786&partnerID=8YFLogxK

U2 - 10.1002/jbm.b.35100

DO - 10.1002/jbm.b.35100

M3 - Article

C2 - 35618683

AN - SCOPUS:85130600786

VL - 110

SP - 2422

EP - 2437

JO - Journal of Biomedical Materials Research - Part B Applied Biomaterials

JF - Journal of Biomedical Materials Research - Part B Applied Biomaterials

SN - 1552-4973

IS - 11

ER -