Gradient nano-engineered in situ forming composite hydrogel for osteochondral regeneration

Radhakrishnan, Janani; Manigandan, Amrutha; Chinnaswamy, Prabu; Subramanian, Anuradha; Sethuraman, Swaminathan

doi:10.1016/j.biomaterials.2018.01.056

Cited by 146 publications

(91 citation statements)

References 43 publications

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“…These scaffolds ensure continuity between phases to avoid a barrier in the interface, together with biomaterials integrity, while mimicking the natural hierarchical structure of the osteochondral tissue. Developed functional materials focused on mimicking specific anisotropic orientation of the subchondral bone and calcified cartilage region in single 3D constructs, demonstrating a favorable control of stem cell fate toward osteogenic and chondrogenic-lineages [17,18]. Cartilage-to-bone engineered strategies mainly rely on scaffold-based approaches due to the tunability and versatility of materials to achieve the mechanical and physical requirements of the tissue for proper regeneration.…”

Section: A Multifactorial Toolbox For Designing Tissue Engineering Stmentioning

confidence: 99%

A Physiology-Inspired Multifactorial Toolbox in Soft-to-Hard Musculoskeletal Interface Tissue Engineering

Calejo

Costa‐Almeida

Reis

et al. 2020

Trends in Biotechnology

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Section: A Multifactorial Toolbox For Designing Tissue Engineering Stmentioning

confidence: 99%

A Physiology-Inspired Multifactorial Toolbox in Soft-to-Hard Musculoskeletal Interface Tissue Engineering

Calejo

Costa‐Almeida

Reis

et al. 2020

Trends in Biotechnology

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“…Dotted lines delineate the neotissue from native host tissue. D, defect site; NT, native tissue (Radhakrishnan et al, )…”

Section: The Functions Of Nanoparticles In Osteochondral Engineeringmentioning

confidence: 99%

“…Li, Xianfang, Xuening, Hongsong, & Xingdong, 2014;K. S. Park et al, 2018;Radhakrishnan, Manigandan, Chinnaswamy, Subramanian, & Sethuraman, 2018;Shou-Cang et al, 2011;Tampieri et al, 2011) and nondegradable nanomaterials, such as lipid, dendrimer, silica, and gold nanoparticles have been used (Fedena et al, 2011;Oliveira et al, 2009;G. Wang, Mostafa, Incani, Kucharski, & Uluda g, 2012;W.…”

Section: Drug Deliverymentioning

confidence: 99%

“…Yang et al, 2018;Zhu, Zhu, Zhang, & Shi, 2013). Previously, chondroitin sulfate and hydroxyapatite were used in a nanoengineered composite to facilitate hyaline cartilage regeneration and promote subchondral bone formation, and lateral host-tissue integration ( Figure 5) (Radhakrishnan et al, 2018). Similar to chondroitin sulfate and hydroxyapatite, the synthetic glucocorticoid dexamethasone has been proven to stimulate in vitro osteogenic differentiation.…”

Section: Drug Deliverymentioning

confidence: 99%

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Advances of nanotechnology in osteochondral regeneration

Deng

Zhou

et al. 2019

WIREs Nanomed Nanobiotechnol

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In the past few decades, nanotechnology has proven to be one of the most powerful engineering strategies. The nanotechnologies for osteochondral tissue engineering aim to restore the anatomical structures and physiological functions of cartilage, subchondral bone, and osteochondral interface. As subchondral bone and articular cartilage have different anatomical structures and the physiological functions, complete healing of osteochondral defects remains a great challenge. Considering the limitation of articular cartilage to self‐healing and the complexity of osteochondral tissue, osteochondral defects are in urgently need for new therapeutic strategies. This review article will concentrate on the most recent advancements of nanotechnologies, which facilitates chondrogenic and osteogenic differentiation for osteochondral regeneration. Moreover, this review will also discuss the current strategies and physiological challenges for the regeneration of osteochondral tissue. Specifically, we will summarize the latest developments of nanobased scaffolds for simultaneously regenerating subchondral bone and articular cartilage tissues. Additionally, perspectives of nanotechnology in osteochondral tissue engineering will be highlighted. This review article provides a comprehensive summary of the latest trends in cartilage and subchondral bone regeneration, paving the way for nanotechnologies in osteochondral tissue engineering. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement

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“…In particular, bilayer hydrogels have emerged as a promising platform for osteochondral tissue engineering due to their high water content, tunable biochemical cues and stiffness in each layer, and in situ forming capabilities to deliver cells minimally invasively. Examples of bilayer hydrogels include synthetic polymers that combine hyaluronic acid or chondroitin sulphate into the chondral layer and hydroxyapatite particles embedded into the bone layer (Radhakrishnan, Manigandan, Chinnaswamy, Subramanian, & Sethuraman, 2018;Schutz, Despang, Lode, & Gelinsky, 2014). Other studies have varied both the biochemical cues and the stiffness within each hydrogel layer (Steinmetz, Aisenbrey, Westbrook, Qi, & Bryant, 2015).…”

Section: Introductionmentioning

confidence: 99%

The effects of dynamic compressive loading on human mesenchymal stem cell osteogenesis in the stiff layer of a bilayer hydrogel

Aziz

Eckstein

Ferguson

et al. 2019

J Tissue Eng Regen Med

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Bilayer hydrogels with a soft cartilage‐like layer and a stiff bone‐like layer embedded with human mesenchymal stem cells (hMSCs) are promising for osteochondral tissue engineering. The goals of this work were to evaluate the effects of dynamic compressive loading (2.5% applied strain, 1 Hz) on osteogenesis in the stiff layer and spatially map local mechanical responses (strain, stress, hydrostatic pressure, and fluid velocity). A bilayer hydrogel was fabricated from soft (24 kPa) and stiff (124 kPa) poly (ethylene glycol) hydrogels. With hMSCs embedded in the stiff layer, osteogenesis was delayed under loading evident by lower OSX and OPN expressions, alkaline phosphatase activity, and collagen content. At Day 28, mineral deposits were present throughout the stiff layer without loading but localized centrally and near the interface under loading. Local strains mapped by particle tracking showed substantial equivalent strain (~1.5%) transferring to the stiff layer. When hMSCs were cultured in stiff single‐layer hydrogels subjected to similar strains, mineralization was inhibited. Finite element analysis revealed that hydrostatic pressures ≥~600 Pa correlated to regions lacking mineralization in both hydrogels. Fluid velocities were low (~1–10 nm/s) in the hydrogels with no apparent correlation to mineralization. Mineralization was recovered by inhibiting ERK1/2, indicating cell‐mediated inhibition. These findings suggest that high strains (~1.5%) combined with higher hydrostatic pressures negatively impact osteogenesis, but in a manner that depends on the magnitude of each mechanical response. This work highlights the importance of local mechanical responses in mediating osteogenesis of hMSCs in bilayer hydrogels being studied for osteochondral tissue engineering.

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Gradient nano-engineered in situ forming composite hydrogel for osteochondral regeneration

Cited by 146 publications

References 43 publications

A Physiology-Inspired Multifactorial Toolbox in Soft-to-Hard Musculoskeletal Interface Tissue Engineering

A Physiology-Inspired Multifactorial Toolbox in Soft-to-Hard Musculoskeletal Interface Tissue Engineering

Advances of nanotechnology in osteochondral regeneration

The effects of dynamic compressive loading on human mesenchymal stem cell osteogenesis in the stiff layer of a bilayer hydrogel

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