4.4 Article

Chondrogenic differentiation of mesenchymal stem/stromal cells on 3D porous poly (ε-caprolactone) scaffolds: Effects of material alkaline treatment and chondroitin sulfate supplementation

Journal

JOURNAL OF BIOSCIENCE AND BIOENGINEERING
Volume 129, Issue 6, Pages 756-764

Publisher

SOC BIOSCIENCE BIOENGINEERING JAPAN
DOI: 10.1016/j.jbiosc.2020.01.004

Keywords

Articular cartilage tissue engineering; Bone marrow mesenchymal stem/stromal cells; Chondroitin sulfate; Fused deposition modeling; Hypoxia; Poly (epsilon-caprolactone) scaffolds

Funding

  1. FCT -Portuguese Foundation for Science and Technology [UID/BIO/04565/2020, UID/Multi/04044/2019, UIDB/500022/2020, PTDC/BBB-BMC/5655/2014]
  2. PRECISE e Accelerating progress toward the new era of precision medicine [PAC-PRECISE-LISBOA-01-0145-FEDER - 016394]
  3. Stimuli2BioScaffold (FCT) [PTDC/EMESIS/32554/2017]
  4. Programa Operacional Regional de Lisboa 2020 [007317]
  5. MIT Portugal Program
  6. FCT [SFRH/BD/73970/2010, SFRH/BD/105771/2014]
  7. [POCI-01-0145-FEDER-016800]
  8. Fundação para a Ciência e a Tecnologia [SFRH/BD/73970/2010, PTDC/BBB-BMC/5655/2014] Funding Source: FCT

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Cartilage defects resultant from trauma or degenerative diseases (e.g., osteoarthritis) can potentially be repaired using tissue engineering (TE) strategies combining progenitor cells, biomaterial scaffolds and bio-physical/chemical cues. This work examines promoting chondrogenic differentiation of human bone marrow mesenchymal stem/stromal cells (BM-MSCs) by combining the effects of modified poly (epsilon-caprolactone) (PCL) scaffolds hydrophilicity and chondroitin sulfate (CS) supplementation in a hypoxic 5% oxygen atmosphere. 3D-extruded PCL scaffolds, characterized by mCT, featured a 21 mm(-1) surface area to volume ratio, 390 mm pore size and approximately 100% pore interconnectivity. Scaffold immersion in sodium hydroxide solutions for different periods of time had major effects in scaffold surface morphology, wettability and mechanical properties, but without improvements on cell adhesion. In-situ chondrogenic differentiation of BM-MSC seeded in 3D-extruded PCL scaffolds resulted in higher cell populations and ECM deposition along all scaffold structure, when chondrogenesis was preceded by an expansion phase. Additionally, CS supplementation during BM-MSC expansion was crucial to enhance aggrecan gene expression, known as a hallmark of chondrogenesis. Overall, this study presents an approach to tailor the wettability and mechanical properties of PCL scaffolds and supports the use of CS-supplementation as a biochemical cue in integrated TE strategies for cartilage regeneration. (C) 2020, The Society for Biotechnology, Japan. All rights reserved.

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