Dynamically Crosslinked Poly(ethylene‐glycol) Hydrogels Reveal a Critical Role of Viscoelasticity in Modulating Glioblastoma Fates and Drug Responses in 3D

Sinha, Sauradeep; Ayushman, Manish; Tong, Xinming; Yang, Fan

doi:10.1002/adhm.202202147

Cited by 14 publications

(14 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cartilage repair scaffold materials must exhibit adequate enzymatic degradability, controlled swelling, and biocompatibility. − The hydrogel for tissue engineering is required to have controlled swelling to avoid swelling or deswelling of the hydrogel in normal tissue fluid at pH 7.4 . PBS (pH 7.4) was used as a normal tissue fluid to investigate the microscopic swelling of the BSA-GMA structures.…”

Section: Resultsmentioning

confidence: 99%

Multipatterned Chondrocytes’ Scaffolds by FL-MOPL with a BSA-GMA Hydrogel to Regulate Chondrocytes’ Morphology

Li,

Liu,

Bin

et al. 2024

ACS Appl. Bio Mater.

View full text Add to dashboard Cite

Repairing articular cartilage damage is challenging due to its low regenerative capacity. In vitro, cartilage regeneration is a potential strategy for the functional reconstruction of cartilage defects. A hydrogel is an advanced material for mimicking the extracellular matrix (ECM) due to its hydrophilicity and biocompatibility, which is known as an ideal scaffold for cartilage regeneration. However, chondrocyte culture in vitro tends to dedifferentiate, leading to fibrosis and reduced mechanical properties of the newly formed cartilage tissue. Therefore, it is necessary to understand the mechanism of modulating the chondrocytes' morphology. In this study, we synthesize photo-cross-linkable bovine serum albumin-glycidyl methacrylate (BSA-GMA) with 65% methacrylation. The scaffolds are found to be suitable for chondrocyte growth, which are fabricated by homemade femtosecond laser maskless optical projection lithography (FL-MOPL). The large-area chondrocyte scaffolds have holes with interior angles of triangle (T), quadrilateral (Q), pentagon (P), hexagonal (H), and round (R). The FL-MOPL polymerization mechanism, swelling, degradation, and biocompatibility of the BSA-GMA hydrogel have been investigated. Furthermore, cytoskeleton and nucleus staining reveals that the R-scaffold with larger interior angle is more effective in maintaining chondrocyte morphology and preventing dedifferentiation. The scaffold's ability to maintain the chondrocytes' morphology improves as its shape matches that of the chondrocytes. These results suggest that the BSA-GMA scaffold is a suitable candidate for preventing chondrocyte differentiation and supporting cartilage tissue repair and regeneration. The proposed method for chondrocyte in vitro culture by developing biocompatible materials and flexible fabrication techniques would broaden the potential application of chondrocyte transplants as a viable treatment for cartilage-related diseases.

show abstract

Section: Resultsmentioning

confidence: 99%

Multipatterned Chondrocytes’ Scaffolds by FL-MOPL with a BSA-GMA Hydrogel to Regulate Chondrocytes’ Morphology

Li,

Liu,

Bin

et al. 2024

ACS Appl. Bio Mater.

View full text Add to dashboard Cite

show abstract

“…To characterize the mechanical property of scaffolds, rheological testing was performed using a Discovery HR-2 hybrid rheometer (TA Instruments), as previously reported 36 . Briefly, scaffolds of 0.5 mm thickness and 8 mm diameter were made and equilibrated in PBS overnight.…”

Section: Methodsmentioning

confidence: 99%

Aspirin synergizes with mineral particle-coated macroporous scaffolds for bone regeneration through immunomodulation

Su,

Villicana,

Zhang

et al. 2023

Theranostics

View full text Add to dashboard Cite

Rationale: Mineral particles have been widely used in bone tissue engineering scaffolds due to their osteoconductive and osteoinductive properties. Despite their benefits, mineral particles can induce undesirable inflammation and subsequent bone resorption. Aspirin (Asp) is an inexpensive and widely used anti-inflammatory drug. The goal of this study is to assess the synergistic effect of Asp and optimized mineral particle coating in macroporous scaffolds to accelerate endogenous bone regeneration and reduce bone resorption in a critical-sized bone defect model. Methods: Four commonly used mineral particles with varying composition (hydroxyapatite v.s. tricalcium phosphate) and size (nano v.s. micro) were used. Mineral particles were coated onto gelatin microribbon (µRB) scaffolds. Macrophages (Mφ) were cultured on gelatin µRB scaffolds containing various particles, and Mφ polarization was assessed using PCR and ELISA. The effect of conditioned medium from Mφ on mesenchymal stem cell (MSC) osteogenesis was also evaluated in vitro . Scaffolds containing optimized mineral particles were then combined with varying dosages of Asp to assess the effect in inducing endogenous bone regeneration using a critical-sized cranial bone defect model. In vivo characterization and in vitro cell studies were performed to elucidate the effect of tuning Asp dosage on Mφ polarization, osteoclast (OC) activity, and MSC osteogenesis. Results: Micro-sized tricalcium phosphate (mTCP) particles were identified as optimal in promoting M2 Mφ polarization and rescuing MSC-based bone formation in the presence of conditioned medium from Mφ. When implanted in vivo , incorporating Asp with mTCP-coated µRB scaffolds significantly accelerated endogenous bone formation in a dose-dependent manner. Impressively, mTCP-coated µRB scaffolds containing 20 µg Asp led to almost complete bone healing of a critical-sized cranial bone defect as early as week 2 with no subsequent bone resorption. Asp enhanced M2 Mφ polarization, decreased OC activity, and promoted MSC osteogenesis in a dosage-dependent manner in vivo . These results were further validated using in vitro cell studies. Conclusions: Here, we demonstrate Asp and mineral particle-coated microribbon scaffold provides a promising therapy for repairing critical-sized cranial bone defects via immunomodulation. The leading formulation supports rapid endogenous bone regeneration without the need for exogenous cells or growth factors, making it attractive for translation. Our results also highlight the importance of optimizing mineral particles and Asp dosage to achieve robust bone healing while avoiding bone resorption by targeting Mφ and OCs.

show abstract

“…[ 163 ] More recently, another interesting mechanical property, stress relaxation, was also shown to affect cell fate and drug response. [ 164 ] As such, the supporting matrix for 3D culture should mimic both biochemical and biophysical cues of the native TME.…”

Section: Challenges and Future Perspectivesmentioning

confidence: 99%

3D Biomimetic Models to Reconstitute Tumor Microenvironment In Vitro: Spheroids, Organoids, and Tumor‐on‐a‐Chip

Zhou

et al. 2023

Adv Healthcare Materials

View full text Add to dashboard Cite

Decades of efforts in engineering in vitro cancer models have advanced drug discovery and the insight into cancer biology. However, the establishment of preclinical models that enable fully recapitulating the tumor microenvironment remains challenging owing to its intrinsic complexity. Recent progress in engineering techniques has allowed the development of a new generation of in vitro preclinical models that can recreate complex in vivo tumor microenvironments and accurately predict drug responses, including spheroids, organoids, and tumor‐on‐a‐chip. These biomimetic 3D tumor models are of particular interest as they pave the way for better understanding of cancer biology and accelerating the development of new anticancer therapeutics with reducing animal use. Here, the recent advances in developing these in vitro platforms for cancer modeling and preclinical drug screening, focusing on incorporating hydrogels are reviewed to reconstitute physiologically relevant microenvironments. The combination of spheroids/organoids with microfluidic technologies is also highlighted to better mimic in vivo tumors and discuss the challenges and future directions in the clinical translation of such models for drug screening and personalized medicine.

show abstract

Dynamically Crosslinked Poly(ethylene‐glycol) Hydrogels Reveal a Critical Role of Viscoelasticity in Modulating Glioblastoma Fates and Drug Responses in 3D

Cited by 14 publications

References 77 publications

Multipatterned Chondrocytes’ Scaffolds by FL-MOPL with a BSA-GMA Hydrogel to Regulate Chondrocytes’ Morphology

Multipatterned Chondrocytes’ Scaffolds by FL-MOPL with a BSA-GMA Hydrogel to Regulate Chondrocytes’ Morphology

Aspirin synergizes with mineral particle-coated macroporous scaffolds for bone regeneration through immunomodulation

3D Biomimetic Models to Reconstitute Tumor Microenvironment In Vitro: Spheroids, Organoids, and Tumor‐on‐a‐Chip

Contact Info

Product

Resources

About