Additive manufacturing of cartilage-mimetic scaffolds as off-the-shelf implants for joint regeneration

2021 ◽  
Author(s):  
Bin Wang ◽  
Farhad Chariyev-Prinz ◽  
Ross Burdis ◽  
Kian Eichholz ◽  
Daniel John Kelly
Keyword(s):  
Articular Cartilage ◽  
Additive Manufacturing ◽  
Transforming Growth Factor ◽  
Composite Scaffold ◽  
Cartilage Regeneration ◽  
Type Ii Collagen ◽  
Cartilage Tissue ◽  
Design Strategies ◽  
Biomimetic Scaffolds

Abstract Biomimetic scaffolds that provide a tissue-specific environment to cells are particularly promising for tissue engineering and regenerative medicine applications. The goal of this study was to integrate emerging additive manufacturing and biomaterial design strategies to produce articular cartilage (AC) mimetic scaffolds that could be used as ‘off-the-shelf’ implants for joint regeneration. To this end alginate sulfate, a sulfated glycosaminoglycan (sGAG) mimic, was used to functionalize porous alginate-based scaffolds and to support the sustained release of transforming growth factor-β3 (TGF-β3). Covalent crosslinking dramatically improved the elasticity of the alginate/alginate sulfate scaffolds, while scaffold architecture could be tailored using a directional freezing technique. Introducing such an anisotropic architecture was found to promote mesenchymal stem cell (MSC) infiltration into the scaffold and to direct the orientation of the deposited extracellular matrix, leading to the development of cartilage tissue with a biomimetic zonal architecture. In vitro experiments also demonstrated the capacity of the sulfated scaffolds to both enhance chondrogenesis of MSCs and to control the release of TGF-β3, leading to the development of a tissue rich in sGAG and type II collagen. The scaffolds were further reinforced with a 3D printed PLCL framework, leading to composite implants that were more elastic than those reinforced with PCL, and which better mimicked the bulk mechanical properties of native cartilage tissue. The ability of this composite scaffold to support chondrogenesis was then confirmed within a dynamic culture system. Altogether, these findings demonstrate the potential of such biomimetic scaffolds as putative ‘single-stage’ or ‘off-the-shelf’ strategies for articular cartilage regeneration.

A novel hybrid multichannel biphasic calcium phosphate granule-based composite scaffold for cartilage tissue regeneration

2017 ◽  
Vol 32 (6) ◽  
pp. 775-787 ◽  
Author(s):  
Albert Jung ◽  
Preeti Makkar ◽  
Jhaleh Amirian ◽  
Byong-Taek Lee
Keyword(s):  
Compressive Strength ◽  
Calcium Phosphate ◽  
Biphasic Calcium Phosphate ◽  
Composite System ◽  
Composite Scaffold ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
In Vitro Biocompatibility ◽  
Surface Modified

The objective of the present study was to develop a novel hybrid multichannel biphasic calcium phosphate granule (MCG)-based composite system for cartilage regeneration. First, hyaluronic acid-gelatin (HG) hydrogel was coated onto MCG matrix (MCG-HG). Poly(lactic-co-glycolic acid) (PLGA) microspheres was separately prepared and modified with polydopamine subsequent to BMP-7 loading (B). The surface-modified microspheres were finally embedded into MCG-HG scaffold to develop the novel hybrid (MCG-HG-PLGA-PD-B) composite system. The newly developed MCG-HG-PLGA-PD-B composite was then subjected to scanning electron microscopy, energy dispersive X-ray spectroscopy, Fourier Transform infrared spectroscopy, porosity, compressive strength, swelling, BMP-7 release and in-vitro biocompatibility studies. Results showed that 60% of BMP-7 retained on the granular surface after 28 days. A hybrid MCG-HG-PLGA-PD-B composite scaffold exhibited higher swelling and compressive strength compared to MCG-HG or MCG. In-vitro studies showed that MCG-HG-PLGA-PD-B had improved cell viability and cell proliferation for both MC3T3-E1 pre-osteoblasts and ATDC5 pre-chondrocytes cell line with respect to MCG-HG or MCG scaffold. Our results suggest that a hybrid MCG-HG-PLGA-PD-B composite scaffold can be a promising candidate for cartilage regeneration applications.

scholarly journals Preparation and Characterization of Poly(vinyl alcohol)-chondroitin Sulphate Hydrogel as Scaffolds for Articular Cartilage Regeneration

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Shivani Nanda ◽  
Nikhil Sood ◽  
B. V. K. Reddy ◽  
Tanmay S. Markandeywar
Keyword(s):  
Articular Cartilage ◽  
Chondroitin Sulphate ◽  
Articular Surface ◽  
Rheological Behaviour ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Poly Vinyl Alcohol ◽  
Cross Linking ◽  
Articular Cartilage Regeneration

The aim of the study was to develop PVA-CS hydrogel scaffolds using glutaraldehyde as a cross-linking agent by chemical cross-linking method in order to obtain biomimetic scaffolds for articular cartilage regeneration. The introduction of PVA enhances the mechanical and bioadhesive properties to the native tissue while chondroitin sulphate enhances the glycosaminoglycan content of extracellular matrix. The role of hydrogel as cartilage regeneration scaffold was evaluated by swelling study, porosity, rheological behaviour, in vitro degradation, and quantification of released chondroitin sulphate. In vivo results showed that cross-linked hydrogels repaired defects with no sign of inflammation as it was well anchored to tissue in the formation of new articular surface. It may be concluded that the addition of chondroitin sulphate to the PVA polymer develops a novel composite with significant applications in cartilage tissue engineering.

scholarly journals Dual Delivery of TGF-β3 and Ghrelin in Microsphere/Hydrogel Systems for Cartilage Regeneration

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5732
Author(s):  
Jianjing Lin ◽  
Li Wang ◽  
Jianhao Lin ◽  
Qiang Liu
Keyword(s):  
Growth Factors ◽  
Chondrogenic Differentiation ◽  
Transforming Growth Factor ◽  
Double Emulsion ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Self Healing ◽  
Tissue Formation ◽  
Extraction Technology

Articular cartilage (AC) damage is quite common, but due to AC’s poor self-healing ability, the damage can easily develop into osteoarthritis (OA). To solve this problem, we developed a microsphere/hydrogel system that provides two growth factors that promote cartilage repair: transforming growth factor-β3 (TGF-β3) to enhance cartilage tissue formation and ghrelin synergy TGF-β to significantly enhance the chondrogenic differentiation. The hydrogel and microspheres were characterized in vitro, and the biocompatibility of the system was verified. Double emulsion solvent extraction technology (w/o/w) is used to encapsulate TGF-β3 and ghrelin into microspheres, and these microspheres are encapsulated in a hydrogel to continuously release TGF-β3 and ghrelin. According to the chondrogenic differentiation ability of mesenchymal stem cells (MSCs) in vitro, the concentrations of the two growth factors were optimized to promote cartilage regeneration.

scholarly journals Coculture of hWJMSCs and pACs in Oriented Scaffold Enhances Hyaline Cartilage Regeneration In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Yu Zhang ◽  
Shuyun Liu ◽  
Weimin Guo ◽  
Chunxiang Hao ◽  
Mingjie Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Articular Cartilage ◽  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Human Umbilical Cord ◽  
Cartilage Cells ◽  
Collagen Ii ◽  
Differentiation Status

Seed cells of articular cartilage tissue engineering face many obstacles in their application because of the dedifferentiation of chondrocytes or unstable chondrogenic differentiation status of pluripotent stem cells. To overcome mentioned dilemmas, a simulation of the articular cartilage microenvironment was constructed by primary articular cartilage cells (pACs) and acellular cartilage extracellular matrix- (ACECM-) oriented scaffold cocultured with human umbilical cord Wharton’s jelly-derived mesenchymal stem cells (hWJMSCs) in vitro. The coculture groups showed more affluent cartilage special matrix ingredients including collagen II and aggrecan based on the results of histological staining and western blotting and cut down as many pACs as possible. The RT-PCR and cell viability experiments also demonstrated that hWJMSCs were successfully induced to differentiate into chondrocytes when cultured in the simulated cartilage microenvironment, as confirmed by the significant upregulation of collagen II and aggrecan, while the cell proliferation activity of pACs was significantly improved by cell-cell interactions. Therefore, compared with monoculture and chondrogenic induction of inducers, coculture providing a simulated native articular microenvironment was a potential and temperate way to regulate the biological behaviors of pACs and hWJMSCs to regenerate the hyaline articular cartilage.

Directing Chondrogenesis of Primary Chondrocytes by Exposure to Glucose Concentrations

2015 ◽  
Vol 24 ◽  
pp. 30-42
Author(s):  
Samuel C. Uzoechi ◽  
Kennedy O. Ejeta ◽  
Goddy C. Okoye ◽  
Gideon I. Ndubuka ◽  
Patrick Ugochukwu Agbasi ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Glucose Concentration ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Glycosaminoglycan Synthesis ◽  
Chondrogenic Medium ◽  
Hypoxic Conditions ◽  
Matrix Production ◽  
Engineered Cartilage

Since articular cartilage is avascular, both nutrient supply and metabolic waste excretion depend on diffusion. However, the major cause of the progression of articular cartilage defect is the poor inherent regenerative capacity of chondrocytes which limits the process of cartilage tissue repair. Creation of nutrient gradients in in vitro cell culture, however, can provide a clue on zonal distributions of cells and glycosaminoglycan synthesis throughout the tissue engineered cartilage. We hypothesized that glucose gradient, in combination with growth factors, could induce differences in matrix distributions for articular cartilage regeneration. Chondrocytes were harvested from bovine cartilage and expanded in monolayers. First, either p0 or p2 chondrocytes were differentiated in serum-free chondrogenic medium containing different glucose concentrations supplemented with TGFβ3/dex or IGF-1under hypoxic or normoxic conditions for 7 days in monolayer. The results indicate that cellular metabolism, cell numbers and glycosaminoglycan (GAG) content increased with increase in glucose concentration in all conditions. Aggrecan (AGC) expression consistently increased with decreasing glucose concentration in both normoxic and hypoxic conditions. COL II and COL I expressions increased with increasing glucose concentration up to 5mmol/L. The expression of COMP increased with increasing glucose concentration under hypoxic conditions and interestingly showed an opposite trend under normoxic conditions. However, comparing the chondrogenic capacity of p0 and p2 cells in the different glucose concentrations did not show differences, but the potential of p2 cells was in general lower compared to p0. Hypoxia had stimulatory effects on matrix production compared to normoxia in both passages. Therefore, supplemented glucose concentration in monolayer could induce differences in matrix production, but the chondrogenic potential remained equal. Therefore, this information could be use to a create gradients through a tissue-engineered cartilage.

scholarly journals Effect of different aged cartilage ECM on chondrogenesis of BMSCs in vitro and in vivo

2020 ◽  
Vol 7 (6) ◽  
pp. 583-595
Author(s):  
Xiuyu Wang ◽  
Yan Lu ◽  
Wan Wang ◽  
Qiguang Wang ◽  
Jie Liang ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Current Knowledge ◽  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
Biological Properties ◽  
Cartilage Tissue ◽  
Before And After ◽  
Marrow Mesenchymal Stem Cells

Abstract Extracellular matrix (ECM)-based biomaterials are promising candidates in cartilage tissue engineering by simulating the native microenvironment to regulate the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) without exogenous growth factors. The biological properties of ECM scaffolds are primarily depended on the original source, which would directly influence the chondrogenic effects of the ECM materials. Despite the expanding investigations on ECM scaffolds in recent years, the selection of optimized ECM materials in cartilage regeneration was less reported. In this study, we harvested and compared the articular cartilage ECM from newborn, juvenile and adult rabbits. The results demonstrated the significant differences in the mechanical strength, sulphated glycosaminoglycan and collagen contents of the different aged ECM, before and after decellularization. Consequently, different compositional and mechanical properties were shown in the three ECM-based collagen hydrogels, which exerted age-dependent chondrogenic inducibility. In general, both in vitro and in vivo results suggested that the newborn ECM promoted the most chondrogenesis of BMSCs but led to severe matrix calcification. In contrast, BMSCs synthesized the lowest amount of cartilaginous matrix with minimal calcification with adult ECM. The juvenile ECM achieved the best overall results in promoting chondrogenesis of BMSCs and preventing matrix calcification. Together, this study provides important information to our current knowledge in the design of future ECM-based biomaterials towards a successful repair of articular cartilage.

scholarly journals The Effect of Varying Concentrations and Application Periods of Chondroitinase ABC on Tissue-Engineered Cartilage

2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Eric Tong ◽  
Grace D. O'Connell ◽  
Terri-Ann N. Kelly ◽  
Clark T. Hung
Keyword(s):  
Mechanical Properties ◽  
Articular Cartilage ◽  
Treatment Option ◽  
Type Ii Collagen ◽  
Treated Group ◽  
Cartilage Tissue ◽  
Type Ii ◽  
Chondroitinase Abc ◽  
Engineered Cartilage

Osteoarthritis, a chronic malady characterized by joint pain and swelling, is caused by damage to articular cartilage and is perpetuated by low-grade inflammation.  Treatments for osteoarthritis do exist, but many treatments focus on coping with the disease rather than curing it.  Surgical options that replace damaged cartilage tissue with that of donor cartilage tissue or cartilage tissue from other parts of articular joints face complications especially when the tissue is not of the correct size or does not have native-like properties. A more suitable treatment option for osteoarthritis is to develop an in vitro tissue-engineered cartilage construct that can be grown using the patient’s own cells and to surgically remove the patient’s damaged cartilage and replace it with the tissue-engineered cartilage. A challenge in developing such a treatment option is producing tissue-engineered cartilage with mechanical properties akin to those of native human articular cartilage. This challenge may be overcome by maximizing the production of type II collagen by the chondrocytes in vitro. One way to maximize collagen production is through the application of chondroitinase ABC, an enzyme which temporarily suppresses proteoglycans in the cartilage matrix to create more space for type II collagen to develop. In this study, two two levels of cABC treatment were applied (“high” and “low”) to cartilage tissue constructs. The “low” cABC treated group received daily feeding of 0.075 U/mL from day 14 to 21 followed by a replacement of chondrogenic media without cABC.  The “high” cABC treated group received a single addition of 0.15 U/mL from day 14 to 16 followed by a replacement of chondrogenic media without cABC.  At the end of 42 days, the constructs were subjected to mechanical testing and biochemical analyses. These analyses showed that the high cABC treatment yielded more native-like mechanical properties when compared to the low cABC treatment and the control results.  Biochemical and histological analyses confirmed that the proteoglycan and collagen II content were higher in the low and high cABC treated groups when compared to the control. All analyses show that the most efficient application of chondroitinase ABC is through a two day duration treatment of a higher concentration (0.15 U/mL).

scholarly journals Combinatorial screening of biochemical and physical signals for phenotypic regulation of stem cell–based cartilage tissue engineering

2020 ◽  
Vol 6 (21) ◽  
pp. eaaz5913 ◽  
Author(s):  
Junmin Lee ◽  
Oju Jeon ◽  
Ming Kong ◽  
Amr A. Abdeen ◽  
Jung-Youn Shin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Articular Cartilage ◽  
Wnt Signaling Pathway ◽  
Cartilage Tissue Engineering ◽  
Cartilage Tissue ◽  
Tissue Formation ◽  
Design Strategies ◽  
Rgd Peptides

Despite great progress in biomaterial design strategies for replacing damaged articular cartilage, prevention of stem cell-derived chondrocyte hypertrophy and resulting inferior tissue formation is still a critical challenge. Here, by using engineered biomaterials and a high-throughput system for screening of combinatorial cues in cartilage microenvironments, we demonstrate that biomaterial cross-linking density that regulates matrix degradation and stiffness—together with defined presentation of growth factors, mechanical stimulation, and arginine-glycine-aspartic acid (RGD) peptides—can guide human mesenchymal stem cell (hMSC) differentiation into articular or hypertrophic cartilage phenotypes. Faster-degrading, soft matrices promoted articular cartilage tissue formation of hMSCs by inducing their proliferation and maturation, while slower-degrading, stiff matrices promoted cells to differentiate into hypertrophic chondrocytes through Yes-associated protein (YAP)–dependent mechanotransduction. in vitro and in vivo chondrogenesis studies also suggest that down-regulation of the Wingless and INT-1 (WNT) signaling pathway is required for better quality articular cartilage-like tissue production.

scholarly journals Chondroitin Sulphate and Gas Foaming Concurrently Improve Articular Cartilage Regeneration in Electrospun Poly(L-lactide-co-ε-caprolactone)/Silk Fibroin Based Scaffolds

2021 ◽  
Author(s):  
Yujie Chen ◽  
Wei Xu ◽  
Muhammad Shafiq ◽  
Daiying Song ◽  
Xianrui Xie ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Silk Fibroin ◽  
Three Dimensional ◽  
Cartilage Regeneration ◽  
The Other ◽  
Cartilage Tissue ◽  
High Porosity ◽  
Freeze Dried ◽  
Gas Foaming

Abstract Degenerated cartilage tissues remain a burgeoning issue to be tackled, while bioactive engineering products available for optimal cartilage regeneration are scarce. In the present study, two-dimensional (2DS) poly(L-lactide-co-ε-caprolactone)/silk fibroin (PLCL/SF)-based scaffolds were fabricated by conjugate electrospinning method, and then cross-linked with chondroitin sulfate (CS) to further enhance their mechanical and biological performance. Afterwards, three-dimensional PLCL/SF scaffolds (3DS) and CS-crosslinked three-dimensional scaffolds (3DCSS) with tailored size were successfully fabricated by in situ gas foaming in a confined mold and subsequently freeze-dried. Gas-foamed scaffolds exhibited high porosity, rapid water absorption, and stable mechanical properties. While all of the scaffolds exhibited excellent cytocompatibility in vitro; 3DCSS showed better cell seeding efficiency and chondro-protective effect as compared to the other scaffolds. Histological analysis of chondrocytes-seeded constructs after cultivation for up to 6 weeks in vitro also confirmed that 3DCSS scaffolds supported the formation of cartilage-like tissues along with the more secretion of cartilage-specific extracellular matrix than that of the other groups. The reparative potential of 3DCSS was further evaluated in an articular cartilage defect model in rabbits, which exhibited a well-integrated boundary and attenuated inflammation demonstrating less expression of pro-inflammatory cytokines, such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α. Taken together, the engineered biomimetic 3DCSS may provide a well-suited therapeutic option for cartilage tissue regeneration applications.

scholarly journals Identifying the Potential of Qur’anic Recitation on the Proliferation of Chondrocytes Derived from Rabbit Articular Cartilage: Work in Progress

2018 ◽  
Vol 17 (1) ◽  
Author(s):  
Rosyafirah Hashim ◽  
Munirah Sha’ban ◽  
Sarah Rahmat ◽  
Zainul Ibrahim Zainuddin
Keyword(s):  
Tissue Engineering ◽  
Articular Cartilage ◽  
Profile Analysis ◽  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
The Times ◽  
And Control ◽  
Rabbit Articular Cartilage

Introduction: In Islamic practice, the use of Qur’anic recitation in treatment can be traced back to the times of Prophet Muhammad (PBUH). This preliminary study aims to identify the potential of Qur’anic recitation of Surah Al-Fatihah on the proliferation of chondrocytes derived from rabbit articular cartilage. Cartilage tissue engineering offers an alternative way to facilitate cartilage regeneration in-vitro. Materials and Methods: The cellular model was established using a serially cultured and expanded chondrocytes in-vitro. The model was assigned into three groups. The first group was exposed to the Surah Al-Fatihah, recited 17 times based on the five times daily prayer unit (Raka’ah) obligated upon Muslims. The second group was exposed to an Arabic poem recitation. The third group was not exposed to any sound and served as the control. All groups were subjected to the growth profile analysis. The analysis was conducted at different passages starting from passage 0 to passage 3. Results: The results showed that the cells proliferation based on the growth kinetic analysis is higher for the cells exposed with Qur’anic recitation as compared to the Arabic poem and control groups. Conclusions: The proliferation process of the rabbit articular cartilage might be influenced with the use of Qur’anic recitation and as well as Arabic poem recitation. Exposure to the Western poem recitation and mute sound will be added for future study. It is hoped that this study could shed some light on the potential use of the Qur’anic recitation to facilitate cartilage regeneration in tissue engineering studies.

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