Fabrication of Tissue-Engineered Cartilage Grafts With Anatomic Surface Contours for Repair of Large Focal Defects

2013 ◽  
Author(s):  
Brendan L. Roach ◽  
Andrea R. Tan ◽  
Aaron M. Stoker ◽  
James L. Cook ◽  
Keith J. Yeager ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Surgical Intervention ◽  
Articular Surface ◽  
Treatment Options ◽  
Cartilage Tissue ◽  
Osteochondral Grafts ◽  
Cartilage Grafts ◽  
Defect Site ◽  
Articular Surfaces ◽  
Engineered Cartilage

Articular cartilage exhibits a poor healing response to injury that necessitates surgical intervention to repair or replace damaged tissue. Treatment options, however, are dependent on the location and size of the defect site. For small focal defects (<2 cm 2), microfracture is the primary method of treatment [8] despite the production of biologically inferior cartilage. For lesions greater than 10 cm 2 where the articular cartilage loss and morphology of the condyle is distorted, a fresh osteoarticular allograft is most likely to succeed [3], while posing a significant surgical challenge related to the technical demands in restoring congruency of the articular surface (i.e., attaining a flush fit of the graft with the surrounding host cartilage tissue). This requires matching of the donor joint size to provide grafts with similar anatomical surface contours. As there is insufficient supply of suitable cartilage grafts to meet the clinical demand, the development of tissue engineered osteochondral grafts would have significant clinical impact for treatment of cartilage lesions and eventually entire articular surfaces.

scholarly journals Challenges in Fabrication of Tissue-Engineered Cartilage with Correct Cellular Colonization and Extracellular Matrix Assembly

2018 ◽  
Vol 19 (9) ◽  
pp. 2700 ◽  
Author(s):  
Mikko Lammi ◽  
Juha Piltti ◽  
Juha Prittinen ◽  
Chengjuan Qu
Keyword(s):  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Pore Size ◽  
Cartilage Tissue ◽  
Cellular Interactions ◽  
Matrix Assembly ◽  
Small Pore ◽  
Culture Models ◽  
Open Question ◽  
Engineered Cartilage

A correct articular cartilage ultrastructure regarding its structural components and cellularity is important for appropriate performance of tissue-engineered articular cartilage. Various scaffold-based, as well as scaffold-free, culture models have been under development to manufacture functional cartilage tissue. Even decellularized tissues have been considered as a potential choice for cellular seeding and tissue fabrication. Pore size, interconnectivity, and functionalization of the scaffold architecture can be varied. Increased mechanical function requires a dense scaffold, which also easily restricts cellular access within the scaffold at seeding. High pore size enhances nutrient transport, while small pore size improves cellular interactions and scaffold resorption. In scaffold-free cultures, the cells assemble the tissue completely by themselves; in optimized cultures, they should be able to fabricate native-like tissue. Decellularized cartilage has a native ultrastructure, although it is a challenge to obtain proper cellular colonization during cell seeding. Bioprinting can, in principle, provide the tissue with correct cellularity and extracellular matrix content, although it is still an open question as to how the correct molecular interaction and structure of extracellular matrix could be achieved. These are challenges facing the ongoing efforts to manufacture optimal articular cartilage.

Anatomical data on the craniocervical junction and their correlation with degenerative changes in 30 cadaveric specimens

2005 ◽  
Vol 3 (5) ◽  
pp. 379-385 ◽  
Author(s):  
Stefan A. König ◽  
Axel Goldammer ◽  
Hans-Ekkehart Vitzthum
Keyword(s):  
Articular Cartilage ◽  
Articular Surface ◽  
Craniocervical Junction ◽  
Degenerative Changes ◽  
Content Type ◽  
Articular Surfaces ◽  
Anatomical Data ◽  
Grade Ii ◽  
Grade Iii ◽  
Fine Print

>Object. The goal of this project was to measure vertebral dimensions at the craniocervical junction and to investigate degenerative changes in this region and their correlations with the anatomical data. These studies will assist in an understanding of biomechanical conditions in this region, which are clinically relevant in cases of cervicogenic headaches and vertigo. Methods. The authors examined 30 cadaveric specimens obtained from patients ranging in age from 24 to 88 years at death. Measurements of angles of the vertebrae were conducted using an imprint method. Microsections of osseous endplates and articular cartilage were graded according to their degrees of degeneration by using the Petersson classification (0, no sign of degeneration; I, superficial degeneration with several fragmentations; II, deeper degeneration with cartilaginous disintegration and penetrating ulceration; or III, complete cartilaginous degeneration with the appearance of subchondral bone in > 50% of the articular surface). The authors found Grade I changes in 100% of the occiput specimens. In the superior articular cartilage of C-1 no changes (Grade 0) were found in two specimens, whereas 6% of the specimens exhibited Grade II changes and 89% exhibited Grade I changes. In the inferior articular cartilage of C-1, 57% of the specimens displayed Grade I changes, 14% Grade II, and 20% Grade III changes. In the superior articular cartilage of C-2, 62.5% of the specimens displayed Grade I changes and 25% Grade II changes. At the occiput—C1 level the authors found a higher frequency of degeneration at the upper left articular surface of the atlas (Quadrants 1 and 3), and at the C1–2 level they found a higher frequency of degeneration at the upper left and upper right articular surfaces of the axis (Quadrants 2 and 3, respectively). Using the McNemar test, the authors investigated the frequency of affection of single quadrants in a left—right side comparison (lateral reversal). Significant differences were identified for Quadrant 2 of the upper left articular surface of C-2 and Quadrant 3 of the upper right articular surface of C-2. These results correlate with the analysis of single articular surfaces of the axis, but contradict the results for the atlas, in which no significant difference in the left—right side comparison was found. Conclusions. Severe degeneration in the atlantooccipital joints appears to be a rare condition, with no Grade II or III degeneration found in the occipital condyles and 6% Grade I, 89% Grade II, but no Grade III changes in the superior articular cartilage of the atlas. Degeneration of the inferior articular cartilage of C-1 and the superior articular cartilage of C-2 indicates that the atlantoaxial joint faces more intense mechanical exposure, which is increased at the upper joint surfaces.

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.

A Comparison of Friction Measurements of Intact Articular Cartilage in Contact with Cartilage, Glass, and Metal

2019 ◽  
Vol 41 ◽  
pp. 23-35 ◽  
Author(s):  
Lyndsey R. Hayden ◽  
Sarah Escaro ◽  
Dewey R. Wilhite ◽  
R. Reid Hanson ◽  
Robert L. Jackson
Keyword(s):  
Articular Cartilage ◽  
Subchondral Bone ◽  
Normal Force ◽  
Articular Surface ◽  
Carpal Bone ◽  
Friction Testing ◽  
Articular Surfaces ◽  
The Coefficient Of Friction ◽  
Friction Measurements ◽  
Counter Surface

The goal of this study was to develop a method of friction testing utilizing cartilage counter surfaces with a complete subchondral bone plate and compare the results to the cartilage on glass and metal (steel) counter surfaces. Articular cartilage surfaces with the underlying subchondral bone intact were not isolated through plug removal. Friction testing was completed using a tribometer (n=16). The coefficient of friction (COF) was measured between the proximal articular surfaces of the second carpal bone when brought into contact with the articular surface of the distal radial facet. The COF of the distal radial facet was obtained with glass and metal counter surfaces. Cartilage-cartilage interfaces yielded the lowest COF when a normal force of 5N and 10N was applied. No statistically significant increase in COF was noted for any combination when an increased normal force was applied (10N), although an increase was observed when glass and metal was in contact with cartilage. COF significantly increased when comparing the cartilage counter surface to metal under an applied load of 5N (p=0.0002). When a 10N load was applied, a significant increase in the COF was observed when comparing the cartilage counter surface to both the glass and metal counter surfaces (p=0.0123 and p < 0.0001 respectively). Results have shown that the described methodology was accurate, repeatable, and emulates physiologic conditions when determining the friction coefficient. The determined COF of cartilage against cartilage is significantly lower than cartilage against metal or glass.

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 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 Fabrication and In Vitro Study of Tissue-Engineered Cartilage Scaffold Derived from Wharton’s Jelly Extracellular Matrix

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Tongguang Xiao ◽  
Weimin Guo ◽  
Mingxue Chen ◽  
Chunxiang Hao ◽  
Shuang Gao ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Cartilage Tissue Engineering ◽  
Wharton’S Jelly ◽  
Immunofluorescent Staining ◽  
Cartilage Tissue ◽  
Wharton's Jelly ◽  
Engineered Cartilage

The scaffold is a key element in cartilage tissue engineering. The components of Wharton’s jelly are similar to those of articular cartilage and it also contains some chondrogenic growth factors, such as insulin-like growth factor I and transforming growth factor-β. We fabricated a tissue-engineered cartilage scaffold derived from Wharton’s jelly extracellular matrix (WJECM) and compared it with a scaffold derived from articular cartilage ECM (ACECM) using freeze-drying. The results demonstrated that both WJECM and ACECM scaffolds possessed favorable pore sizes and porosities; moreover, they showed good water uptake ratios and compressive moduli. Histological staining confirmed that the WJECM and ACECM scaffolds contained similar ECM. Moreover, both scaffolds showed good cellular adherence, bioactivity, and biocompatibility. MTT and DNA content assessments confirmed that the ACECM scaffold tended to be more beneficial for improving cell proliferation than the WJECM scaffold. However, RT-qPCR results demonstrated that the WJECM scaffold was more favorable to enhance cellular chondrogenesis than the ACECM scaffold, showing more collagen II and aggrecan mRNA expression. These results were confirmed indirectly by glycosaminoglycan and collagen content assessments and partially confirmed by histology and immunofluorescent staining. In conclusion, these results suggest that a WJECM scaffold may be favorable for future cartilage tissue engineering.

The Effect of Antibody Size and Mechanical Loading on Solute Diffusion Through the Articular Surface of Cartilage

2017 ◽  
Vol 139 (9) ◽  
Author(s):  
Chris D. DiDomenico ◽  
Andrew Goodearl ◽  
Anna Yarilina ◽  
Victor Sun ◽  
Soumya Mitra ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Mechanical Loading ◽  
Articular Surface ◽  
Solute Diffusion ◽  
Cartilage Tissue ◽  
Tissue Penetration ◽  
Transport Enhancement ◽  
Healthy Cartilage ◽  
Heterogeneous Nature ◽  
Therapeutic Molecules

Because of the heterogeneous nature of articular cartilage tissue, penetration of potential therapeutic molecules for osteoarthritis (OA) through the articular surface (AS) is complex, with many factors that affect transport of these solutes within the tissue. Therefore, the goal of this study is to investigate how the size of antibody (Ab) variants, as well as application of cyclic mechanical loading, affects solute transport within healthy cartilage tissue. Penetration of fluorescently tagged solutes was quantified using confocal microscopy. For all the solutes tested, fluorescence curves were obtained through the articular surface. On average, diffusivities for the solutes of sizes 200 kDa, 150 kDa, 50 kDa, and 25 kDa were 3.3, 3.4, 5.1, and 6.0 μm2/s from 0 to 100 μm from the articular surface. Diffusivities went up to a maximum of 16.5, 18.5, 20.5, and 23.4 μm2/s for the 200 kDa, 150 kDa, 50 kDa, and 25 kDa molecules, respectively, from 225 to 325 μm from the surface. Overall, the effect of loading was very significant, with maximal transport enhancement for each solute ranging from 2.2 to 3.4-fold near 275 μm. Ultimately, solutes of this size do not diffuse uniformly nor are convected uniformly, through the depth of the cartilage tissue. This research potentially holds great clinical significance to discover ways of further optimizing transport into cartilage and leads to effective antibody-based treatments for OA.

Transport Phenomena in Engineered Cartilage With Tissue Development in Agarose Gel

2007 ◽  
Author(s):  
Y. Kitajima ◽  
S. Sugino ◽  
T. Sanada ◽  
Y. Sawae ◽  
T. Murakami ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Diffusion Coefficients ◽  
Transport Phenomena ◽  
Weight Percent ◽  
Flow Chamber ◽  
Transport Processes ◽  
Cartilage Tissue ◽  
Agarose Gel ◽  
Tissue Development ◽  
Engineered Cartilage

The primary function of articular cartilage is to absorb impact in life cycle, however once cartilage is damaged, it has poor ability to recover. And then transplant of engineered cartilage tissue is considered as the promising measure for the therapeutic approach, since it is free from immune reaction. Articular cartilage consists of 2% chondrocyte and 98% extra-cellar-matrix (ECM), which is made by chondrocyte’s metabolic action. ECM shows high osmotic pressure, mainly due to highly negative charged proteoglycan, and hence retain large amount of water. The most characteristic nature of cartilage tissue is avascularity, hence materials, such as nutrition and wastes, are transported from connective tissue or periosteum by mainly diffusion. One of the most significant key factors to control the development of the engineered cartilage is this transport phenomenon, which is, on the other hand, strongly affected by the tissue development. Therefore we study transport processes as ECM development. In this study, we selected ultra-low gelling temperature agarose gel, of different types and weight percent, as the scaffold, and chondrocytes were isolated from the bovine metacarpal-phalangeal joint. Engineered cartilage was obtained by incubating cell-agarose compounds for ECM to be produced. Engineered cartilage tissue specimens were soaked with fluorescent labeled dextran of prescribed molecular weight to observe the diffusion transport process. We evaluated diffusion coefficients by two different methods, namely, global observation in specimen by using flow chamber and local observation diffusion using FRAP method. We compare coefficients of dextran molecules both in engineered cartilage and cell-free agarose gel. First we investigate the effects of tissue development on diffusion coefficients. We observe the effects of incubation periods on the diffusion coefficients of engineered cartilage. And then we investigate the charge effects on the transport phenomena, by comparing the transport processes of charged and uncharged dextran. We also investigate the effects of scaffold type on tissue development.

Repair of Osteochondral Defects With Predifferentiated Mesenchymal Stem Cells of Distinct Phenotypic Character Derived From a Nanotopographic Platform

2020 ◽  
Vol 48 (7) ◽  
pp. 1735-1747
Author(s):  
Yingnan Wu ◽  
Zheng Yang ◽  
Vinitha Denslin ◽  
XiaFei Ren ◽  
Chang Sheng Lee ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Cartilage Defects ◽  
Defect Site

Background: Articular cartilage has a zonal architecture and biphasic mechanical properties. The recapitulation of surface lubrication properties with high compressibility of the deeper layers of articular cartilage during regeneration is essential in achieving long-term cartilage integrity. Current clinical approaches for cartilage repair, especially with the use of mesenchymal stem cells (MSCs), have yet to restore the hierarchically organized architecture of articular cartilage. Hypothesis: MSCs predifferentiated on surfaces with specific nanotopographic patterns can provide phenotypically stable and defined chondrogenic cells and, when delivered as a bilayered stratified construct at the cartilage defect site, will facilitate the formation of functionally superior cartilage tissue in vivo. Study Design: Controlled laboratory study. Methods: MSCs were subjected to chondrogenic differentiation on specific nanopatterned surfaces. The phenotype of the differentiated cells was assessed by the expression of cartilage markers. The ability of the 2-dimensional nanopattern-generated chondrogenic cells to retain their phenotypic characteristics after removal from the patterned surface was tested by subjecting the enzymatically harvested cells to 3-dimensional fibrin hydrogel culture. The in vivo efficacy in cartilage repair was demonstrated in an osteochondral rabbit defect model. Repair by bilayered construct with specific nanopattern predifferentiated cells was compared with implantation with cell-free fibrin hydrogel, undifferentiated MSCs, and mixed-phenotype nanopattern predifferentiated MSCs. Cartilage repair was evaluated at 12 weeks after implantation. Results: Three weeks of predifferentiation on 2-dimensional nanotopographic patterns was able to generate phenotypically stable chondrogenic cells. Implantation of nanopatterned differentiated MSCs as stratified bilayered hydrogel constructs improved the repair quality of cartilage defects, as indicated by histological scoring, mechanical properties, and polarized microscopy analysis. Conclusion: Our results indicate that with an appropriate period of differentiation, 2-dimensional nanotopographic patterns can be employed to generate phenotypically stable chondrogenic cells, which, when implanted as stratified bilayered hydrogel constructs, were able to form functionally superior cartilage tissue. Clinical Relevance: Our approach provides a relatively straightforward method of obtaining large quantities of zone-specific chondrocytes from MSCs to engineer a stratified cartilage construct that could recapitulate the zonal architecture of hyaline cartilage, and it represents a significant improvement in current MSC-based cartilage regeneration.

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