다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

Cartilage regeneration and repair remain a clinical challenge due to the limited capability of cartilage to self-regenerate. Worldwide, the costs associated with cartilage regeneration per patient are estimated on average £30 000 for producing and supplying cells. Regenerative approaches may include the use of cell therapies and tissue engineering by combining relevant cells, scaffolds and instructive biomolecules to stimulate or modulate cartilage repair. Hydrogels have been of great interest within these fields to be used as 3D substrates to cultivate and grow cartilage cells. Currently, biomimetic hydrogels with adequate biological and physicochemical properties, such as mechanical properties, capable of supporting load-bearing capability, are yet to succeed. In this review, biomaterials’ advantages and disadvantages for the manufacturing of biomimetic hydrogels for cartilage regeneration are presented. Different studies on the formulation of cartilage-like hydrogels based on materials such as gelatin, chondroitin sulfate, hyaluronic acid and polyethylene glycol are summarised and contrasted in terms of their mechanical properties (e.g. elastic modulus) and ability to enhance cell function such as cell viability and GAG content. Current limitations and challenges of biomimetic hydrogels for cartilage regeneration are also presented.

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Biomimetic hydrogels designed for cartilage tissue engineering

Chitosan hydrogel/3D-printed poly(ε-caprolactone) hybrid scaffold containing synovial mesenchymal stem cells for cartilage regeneration based on tetrahedral framework nucleic acid recruitment.

van Gastel, N., Stegen, S., Eelen, G., Schoors, S., Carlier, A., Daniels, V. W., Baryawno, N., Przybylski, D., Depypere, M., Stiers, P-J., Lambrechts, D., Van Looveren, R., Torrekens, S., Sharda, A., Agostinis, P., Lambrechts, D., Maes, F., Swinnen, J., Geris, L., ... Carmeliet, G. (2020). Lipid availability determines fate of skeletal progenitor cells via SOX9. Nature, 579(7797), 111-117. https://doi.org/10.1038/s41586-0202050-1

/pdf/lipid-availability-determines-fate-of-skeletal-progenitor-4u58oloeoy.pdf

Lipid availability determines fate of skeletal progenitor cells via SOX9

Clinically, microfracture is the most commonly applied surgical technique for cartilage defects. However, an increasing number of studies have shown that the clinical improvement remains questionable, and the reason remains unclear. Notably, recent discoveries revealed that signals from regenerated niches play a critical role in determining mesenchymal stem cell fate specification and differentiation. We speculate that a microenvironmentally optimized scaffold that directs mesenchymal stem cell fate will be a good therapeutic strategy for cartilage repair. Therefore, we first explored the deficiency of microfractures in cartilage repair. The microfracture not only induced inflammatory cell aggregation in blood clots but also consisted of loose granulation tissue with increased levels of proteins related to fibrogenesis. We then fabricated a functional cartilage scaffold using two strong bioactive cues, transforming growth factor-β3 and decellularized cartilage extracellular matrix, to modulate the cell fate of mesenchymal stem cells. Additionally, poly(ε-caprolactone) was also coprinted with extracellular matrix-based bioinks to provide early mechanical support. The in vitro studies showed that microenvironmentally optimized scaffolds exert powerful effects on modulating the mesenchymal stem cell fate, such as promoting cell migration, proliferation and chondrogenesis. Importantly, this strategy achieved superior regeneration in sheep via scaffolds with biomechanics (restored well-organized collagen orientation) and antiapoptotic properties (cell death-related genes were also downregulated). In summary, this study provides evidence that microenvironmentally optimized scaffolds improve cartilage regeneration in situ by regulating the microenvironment and support further translation in human cartilage repair. STATEMENT OF SIGNIFICANCE: Although microfracture (MF)-based treatment for chondral defects has been commonly used, critical gaps exist in understanding the biochemistry of MF-induced repaired tissue. More importantly, the clinically unsatisfactory effects of MF treatment have prompted researchers to focus on tissue engineering scaffolds that may have sufficient therapeutic efficacy. In this manuscript, a 3D printing ink containing cartilage tissue-specific extracellular matrix (ECM), methacrylate gelatin (GelMA), and transforming growth factor-β3 (TGF-β3)-embedded polylactic-coglycolic acid (PLGA) microspheres was coprinted with poly(ε-caprolactone) (PCL) to fabricate tissue engineering scaffolds for chondral defect repair. The sustained release of TGF-β3 from scaffolds successfully directed endogenous stem/progenitor cell migration and differentiation. This microenvironmentally optimized scaffold produced improved tissue repair outcomes in the sheep animal model, explicitly guiding more organized neotissue formation and therefore recapitulating the anisotropic structure of native articular cartilage. We hypothesized that the cell-free scaffolds might improve the clinical applicability and become a new therapeutic option for chondral defect repair.

Microenvironmentally optimized 3D-printed TGFβ-functionalized scaffolds facilitate endogenous cartilage regeneration in sheep.

Kgn Releasing Ducwj Scaffold Promotes Rotator Cuff Fibrocartilaginous Interface Regeneration

The goal of meniscal tissue engineering is tissue remodeling and functional recovery. Autologous, tissue-engineered adipose-derived stem cell (ADSC) sheets promote meniscal regeneration in rabbit meniscal defects in vivo. Moreover, compared with a control group, in the ADSC sheet model, both histologic scores and gene expression are more similar to normal meniscal tissue. ADSC sheets promote meniscal regeneration regardless of whether the defect involves the whole width or inner half of a meniscal defect. Mechanical properties are also important, and experimental data show encouraging mechanical properties of meniscus tissue reconstructed from ADSC sheets. Cell sheet technology is a promising therapeutic strategy for meniscal regenerative medicine and tissue engineering. Theoretically, cell sheet transplantation could result in superior outcomes to traditional cell-free scaffolds, and further research is needed before clinical application. 

Hao Li

Papers

Microenvironmentally optimized 3D-printed TGFβ-functionalized scaffolds facilitate endogenous cartilage regeneration in sheep.

Kgn Releasing Ducwj Scaffold Promotes Rotator Cuff Fibrocartilaginous Interface Regeneration

Editorial Commentary: Meniscus Regeneration Based on Adipose-Derived Stem Cells: How Far Are We From Clinical Application?