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- Title
Guiding Stem Cell Tenogenesis by Modulation of Growth Factor Signaling and Cell‐Scale Biophysical Cues in Bioengineered Constructs.
- Authors
Teixeira, Simão P. B.; Pardo, Alberto; Bakht, Syeda M.; Gomez‐Florit, Manuel; Reis, Rui L.; Gomes, Manuela E.; Domingues, Rui M. A.
- Abstract
Tendon injuries and tendinopathies are increasingly prevalent health problems currently lacking effective treatments. Tissue engineering offers promising strategies to boost the low innate regenerative ability of tendons. Within this context, the simultaneous leveraging of both physical and biochemical cues by engineered scaffolding systems can be explored to promote a stronger tenogenic response from stem cells. Here, molecularly imprinted polymeric nanoparticles (MINPs) against transforming growth factor (TGF)‐β3 are combined with bioinspired anisotropic hydrogels to produce tenogenesis‐inductive constructs. MINPs are first solid phase‐imprinted against a TGF‐β3 epitope, achieving an affinity comparable to monoclonal antibodies. MINPs and magnetically‐responsive microfibers are then encapsulated together with adipose‐derived stem cells within gelatin‐based hydrogels, applying a magnetostatic field during gelation to align the microfibers. The created anisotropic microstructure guides cell growth and elongation unidirectionally, while MINPs act as artificial receptors for TGF‐β3, potentiating its paracrine action in the cellular microenvironment. The combination of both stimuli proves effective at increasing TGF‐β signaling, which promotes the expression of tendon‐associated genes and corresponding protein synthesis, suggesting that microstructural cues and biomolecule sequestration act in tandem to direct cell fate commitment. Overall, this system recapitulates several elements of tendon development, constituting a promising strategy for the regeneration of this tissue.
- Subjects
GROWTH factors; STEM cells; TRANSFORMING growth factors; IMPRINTED polymers; MAGNETIC fields; TENDON injuries; SYNTHETIC receptors
- Publication
Advanced Functional Materials, 2024, Vol 34, Issue 29, p1
- ISSN
1616-301X
- Publication type
Article
- DOI
10.1002/adfm.202312961