<scp>C</scp>ontinuous multilayered composite hydrogel as osteochondral substitute

Leone, Gemma; Volpato, M. D.; Nelli, Nicola; Lamponi, Stefania; Boanini, Elisa; Bigi, Adriana; Magnani, Agnese

doi:10.1002/jbm.a.35389

Cited by 26 publications

(12 citation statements)

References 30 publications

(52 reference statements)

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“…PVA and modified PVA hydrogels with a modulus of 1 to 5 MPa have been developed to repair cartilage tissues [65–70]. However, PVA is non-biodegradable so that it can only be used as permanent cartilage implant.…”

Section: Designing Hydrogels For Reconstruction Of Osteochondral Imentioning

confidence: 99%

Cell-laden hydrogels for osteochondral and cartilage tissue engineering

et al. 2017

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Despite tremendous advances in the field of regenerative medicine, it still remains challenging to repair the osteochondral interface and full-thickness articular cartilage defects. This inefficiency largely originates from the lack of appropriate tissue engineered artificial matrices that can replace the damaged regions and promote tissue regeneration. Hydrogels are emerging as a promising class of biomaterials for both soft and hard tissue regeneration. Many critical properties of hydrogels, such as mechanical stiffness, elasticity, water content, bioactivity, and degradation, can be rationally designed and conveniently tuned by proper selection of the material and chemistry. Particularly, advances in the development of cell-laden hydrogels have opened up new possibilities for cell therapy. In this article, we describe the problems encountered in this field and review recent progress in designing cell-hydrogel hybrid constructs for promoting the reestablishment of osteochondral/cartilage tissues. Our focus centers on the effects of hydrogel type, cell type, and growth factor delivery on achieving efficient chondrogenesis and osteogenesis. We give our perspective on developing next-generation matrices with improved physical and biological properties for osteochondral/cartilage tissue engineering. We also highlight recent advances in biomanufacturing technologies (e.g. molding, bioprinting, and assembly) for fabrication of hydrogel-based osteochondral and cartilage constructs with complex compositions and microarchitectures to mimic their native counterparts.

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Section: Designing Hydrogels For Reconstruction Of Osteochondral Imentioning

confidence: 99%

Cell-laden hydrogels for osteochondral and cartilage tissue engineering

et al. 2017

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“…As already reported, for samples tested in native status, a great difference was observed in the region 30–200°C relative to total water loss. Another significant difference was seen in terms of R , that is the ratio between the weight loss in region 200–400°C, relative to the free carbon chain, and the weight loss in region 400–600°C, relative to condensed and more structured carbon component (Leone et al, ). The higher the R value, the softer is the matrix.…”

Section: Resultsmentioning

confidence: 99%

Homogentisic acid induces morphological and mechanical aberration of ochronotic cartilage in alkaptonuria

Bernardini

Leone

Millucci

et al. 2018

Journal Cellular Physiology

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Alkaptonuria (AKU) is a disease caused by a deficient homogentisate 1,2-dioxygenase activity leading to systemic accumulation of homogentisic acid (HGA), that forms a melanin-like polymer that progressively deposits onto connective tissues causing a pigmentation called "ochronosis" and tissue degeneration. The effects of AKU and ochronotic pigment on the biomechanical properties of articular cartilage need further investigation. To this aim, AKU cartilage was studied using thermal (thermogravimetry and differential scanning calorimetry) and rheological analysis.We found that AKU cartilage had a doubled mesopore radius compared to healthy cartilage. Since the mesoporous structure is the main responsible for maintaining a correct hydrostatic pressure and tissue homoeostasis, drastic changes of thermal and rheological parameters were found in AKU. In particular, AKU tissue lost its capability to enhance chondrocytes metabolism (decreased heat capacity) and hence the production of proteoglycans. A drastic increase in stiffness and decrease in dissipative and lubricant role ensued in AKU cartilage. Multiphoton and scanning electron microscopies revealed destruction of cell-matrix microstructure and disruption of the superficial layer. Such observations on AKU specimens were confirmed in HGAtreated healthy cartilage, indicating that HGA is the toxic responsible of morphological and mechanical alterations of cartilage in AKU. K E Y W O R D Salkaptonuria, glycosaminoglycan, heat capacity, mesoporosity, ochronosis, rheology

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“…[1] Cartilage has a limited ability to self-repair, most often requiring surgical intervention to address damage to this tissue. [2–5] While small fissure, < 2 cm, focal defects in cartilage are asymptomatic, they can slowly grow in size and ultimately lead to osteoarthritis if left untreated. [3] Currently, small defects are treated using techniques such as microfracture and mosaicplasty; however, these techniques often result in the formation of fibrous tissue rather than hyaline cartilage and suffer from poor lateral integration with the surrounding native tissue.…”

Section: Introductionmentioning

confidence: 99%

“…[2, 5, 8–20] Hydrogels can be formed through a variety of methods and recent reviews discuss these strategies. [9, 21, 22] Injectable hydrogel systems, which can be gelled in situ , are advantageous since their applications can be minimally invasive and directly delivered to the damage site.…”

Section: Introductionmentioning

confidence: 99%

“…[9] Such injectable hydrogel systems include those based on poly(ethylene glycol),[23–25] gelatin,[26, 27] chitosan,[27, 28] alginate,[29] chondroitin sulfate,[30] carboxymethylcellulose,[31] poly(vinyl alcohol),[32, 33] and HA. [34–39] While implanted materials must be biocompatible and meet the mechanical needs of the tissue,[5, 8, 9] they must also integrate with the surrounding tissue, in this case forming a cartilage-hydrogel interface. Without the formation of a stable interface upon or shortly after repair, the implanted hydrogel may loosen within the defect and eventually fail, requiring further surgical intervention.…”

Section: Introductionmentioning

confidence: 99%

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Photocrosslinked tyramine-substituted hyaluronate hydrogels with tunable mechanical properties improve immediate tissue-hydrogel interfacial strength in articular cartilage

Donnelly

Chen

Finch

et al. 2017

Journal of Biomaterials Science, Polymer Edition

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Articular cartilage lacks the ability to self-repair and a permanent solution for cartilage repair remains elusive. Hydrogel implantation is a promising technique for cartilage repair; however for the technique to be successful hydrogels must interface with the surrounding tissue. The objective of this study was to investigate the tunability of mechanical properties in a hydrogel system using a phenol-substituted polymer, tyramine-substituted hyaluronate (TA-HA), and to determine if the hydrogels could form an interface with cartilage. We hypothesized that tyramine moieties on hyaluronate could crosslink to aromatic amino acids in the cartilage extracellular matrix. Ultraviolet (UV) light and a riboflavin photosensitizer were used to create a hydrogel by tyramine self‐crosslinking. The gel mechanical properties were tuned by varying riboflavin concentration, TA-HA concentration, and UV exposure time. Hydrogels formed with a minimum of 2.5 min of UV exposure. The compressive modulus varied from 5–16 kPa. Fluorescence spectroscopy analysis found differences in dityramine content. Cyanine-3 labelled tyramide reactivity at the surface of cartilage was dependent on the presence of riboflavin and UV exposure time. Hydrogels fabricated within articular cartilage defects had increasing peak interfacial shear stress at the cartilage-hydrogel interface with increasing UV exposure time, reaching a maximum shear stress 3.5× greater than a press‐fit control. Our results found that phenol-substituted polymer/riboflavin systems can be used to fabricate hydrogels with tunable mechanical properties and can interface with the surface tissue, such as articular cartilage.

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Continuous multilayered composite hydrogel as osteochondral substitute

Cited by 26 publications

References 30 publications

Cell-laden hydrogels for osteochondral and cartilage tissue engineering

Cell-laden hydrogels for osteochondral and cartilage tissue engineering

Homogentisic acid induces morphological and mechanical aberration of ochronotic cartilage in alkaptonuria

Photocrosslinked tyramine-substituted hyaluronate hydrogels with tunable mechanical properties improve immediate tissue-hydrogel interfacial strength in articular cartilage

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