scholarly journals Treatment of Focal Cartilage Defects in Minipigs with Zonal Chondrocyte/Mesenchymal Progenitor Cell Constructs

2019 ◽  
Vol 20 (3) ◽  
pp. 653 ◽  
Author(s):  
Friederike Bothe ◽  
Anne-Kathrin Deubel ◽  
Eliane Hesse ◽  
Benedict Lotz ◽  
Jürgen Groll ◽  
...  
Keyword(s):  
Bone Erosion ◽  
Cartilage Regeneration ◽  
Bottom Layer ◽  
Cartilage Defects ◽  
Treatment Groups ◽  
Calcified Cartilage ◽  
Important Challenge ◽  
Zonal Organization

Despite advances in cartilage repair strategies, treatment of focal chondral lesions remains an important challenge to prevent osteoarthritis. Articular cartilage is organized into several layers and lack of zonal organization of current grafts is held responsible for insufficient biomechanical and biochemical quality of repair-tissue. The aim was to develop a zonal approach for cartilage regeneration to determine whether the outcome can be improved compared to a non-zonal strategy. Hydrogel-filled polycaprolactone (PCL)-constructs with a chondrocyte-seeded upper-layer deemed to induce hyaline cartilage and a mesenchymal stromal cell (MSC)-containing bottom-layer deemed to induce calcified cartilage were compared to chondrocyte-based non-zonal grafts in a minipig model. Grafts showed comparable hardness at implantation and did not cause visible signs of inflammation. After 6 months, X-ray microtomography (µCT)-analysis revealed significant bone-loss in both treatment groups compared to empty controls. PCL-enforcement and some hydrogel-remnants were retained in all defects, but most implants were pressed into the subchondral bone. Despite important heterogeneities, both treatments reached a significantly lower modified O’Driscoll-score compared to empty controls. Thus, PCL may have induced bone-erosion during joint loading and misplacement of grafts in vivo precluding adequate permanent orientation of zones compared to surrounding native cartilage.

Combined Effects of Bone Marrow-Derived Mesenchymal Stem Cells and PLGA-PEG-PLGA Scaffolds on Repair of Articular Cartilage Defect

2013 ◽  
Vol 815 ◽  
pp. 345-349 ◽  
Author(s):  
Ching Wen Hsu ◽  
Ping Liu ◽  
Song Song Zhu ◽  
Feng Deng ◽  
Bi Zhang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Articular Cartilage ◽  
Growth Factor ◽  
Cartilage Defect ◽  
Cartilage Regeneration ◽  
Tissue Growth ◽  
Cartilage Defects

Here we reported a combined technique for articular cartilage repair, consisting of bone arrow mesenchymal stem cells (BMMSCs) and poly (dl-lactide-co-glycolide-b-ethylene glycol-b-dl-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymers carried with tissue growth factor (TGF-belat1). In the present study, BMMSCs seeded on PLGA-PEG-PLGA with were incubated in vitro, carried or not TGF-belta1, Then the effects of the composite on repair of cartilage defect were evaluated in rabbit knee joints in vivo. Full-thickness cartilage defects (diameter: 5 mm; depth: 3 mm) in the patellar groove were either left empty (n=18), implanted with BMMSCs/PLGA (n=18), TGF-belta1 modified BMMSCs/PLGA-PEG-PLGA. The defect area was examined grossly, histologically at 6, 24 weeks postoperatively. After implantation, the BMMSCs /PLGA-PEG-PLGA with TGF-belta1 group showed successful hyaline-like cartilage regeneration similar to normal cartilage, which was superior to the other groups using gross examination, qualitative and quantitative histology. These findings suggested that a combination of BMMSCs/PLGA-PEG-PLGA carried with tissue growth factor (TGF-belat1) may be an alternative treatment for large osteochondral defects in high loading sites.

scholarly journals Microfracture Versus Drilling of Articular Cartilage Defects: A Systematic Review of the Basic Science Evidence

2020 ◽  
Vol 8 (8) ◽  
pp. 232596712094531 ◽  
Author(s):  
Matthew J. Kraeutler ◽  
Gianna M. Aliberti ◽  
Anthony J. Scillia ◽  
Eric C. McCarty ◽  
Mary K. Mulcahey
Keyword(s):  
Systematic Review ◽  
Articular Cartilage ◽  
Cartilage Repair ◽  
Basic Science ◽  
Science Studies ◽  
Cartilage Regeneration ◽  
Cartilage Defects ◽  
Repair Tissue ◽  
Marrow Stimulation

Background: Microfracture (MFx) is one of the most common techniques used for the treatment of articular cartilage defects, although recently there has been a trend toward the use of drilling rather than MFx for the treatment of these defects. Purpose: To perform a systematic review of basic science studies to determine the effect of microfracture versus drilling for articular cartilage repair. Study Design: Systematic review. Methods: A systematic review was performed by searching PubMed, the Cochrane Library, and EMBASE to identify basic science studies comparing outcomes of MFx versus drilling. The search phrase used was microfracture AND (drilling OR microdrilling). Inclusion criteria were basic science studies that directly compared the effect of MFx versus drilling on subchondral bone, bone marrow stimulation, and cartilage regeneration. Results: A total of 7 studies met the inclusion criteria and were included in this systematic review. Of these, 4 studies were performed in rabbits, 1 study in sheep, and 2 studies in humans. All of the included studies investigated cartilage repair in the knee. In the animal studies, microfracture produced fractured and compacted bone and led to increased osteocyte necrosis compared with drilling. Deep drilling (6 mm) was superior to both shallow drilling (2 mm) and MFx in terms of increased subchondral hematoma with greater access to marrow stroma, improved cartilage repair, and increased mineralized bone. However, the overall quality of cartilage repair tissue was poor regardless of marrow stimulation technique. In 2 studies that investigated repair tissue after MFx and/or drilling in human patients with osteoarthritis and cartilage defects, the investigators found that cartilage repair tissue did not achieve the quality of normal hyaline articular cartilage. Conclusion: In the limited basic science studies that are available, deep drilling of cartilage defects in the knee resulted in improved biological features compared with MFx, including less damage to the subchondral bone and greater access to marrow stroma. Regardless of marrow stimulation technique, the overall quality of cartilage regeneration was poor and did not achieve the characteristics of native hyaline cartilage. Overall, there is a general lack of basic science literature comparing microfracture versus drilling for focal chondral defects.

scholarly journals Progress and Applications of Polyphosphate in Bone and Cartilage Regeneration

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yan Wang ◽  
Min Li ◽  
Pei Li ◽  
Haijun Teng ◽  
Dehong Fan ◽  
...  
Keyword(s):  
Cartilage Regeneration ◽  
High Energy ◽  
Cartilage Defects ◽  
Artificial Bone ◽  
Cellular Mechanisms ◽  
Inorganic Polyphosphate ◽  
Morphogenetic Effects ◽  
And Cartilage

Patients with bone and cartilage defects due to infection, tumors, and trauma are quite common. Repairing bone and cartilage defects is thus a major problem for clinicians. Autologous and artificial bone transplantations are associated with many challenges, such as limited materials and immune rejection. Bone and cartilage regeneration has become a popular research topic. Inorganic polyphosphate (polyP) is a widely occurring biopolymer with high-energy phosphoanhydride bonds that exists in organisms from bacteria to mammals. Much data indicate that polyP acts as a regulator of gene expression in bone and cartilage tissues and exerts morphogenetic effects on cells involved in bone and cartilage formation. Exposure of these cells to polyP leads to the increase of cytokines that promote the differentiation of mesenchymal stem cells into osteoblasts, accelerates the osteoblast mineralization process, and inhibits the differentiation of osteoclast precursors to functionally active osteoclasts. PolyP-based materials have been widely reported in in vivo and in vitro studies. This paper reviews the current cellular mechanisms and material applications of polyP in bone and cartilage regeneration.

scholarly journals Investigation of molecular parameters on cartilage regeneration in experimental models of cartilage defects and osteoarthritis

2014 ◽  
Author(s):  
Ελευθέριος Μακρής
Keyword(s):  
Cartilage Regeneration ◽  
Experimental Models ◽  
Cartilage Defects ◽  
Molecular Parameters

Ο αρθρικός και ο ινώδης χόνδρος έχουν περιορισμένη ικανότητα αναγέννησης μετά από τραυματικές κακώσεις και παθήσεις των αρθρώσεων. Δεδομένου του κριτικού ρόλου των ιστών αυτών στην προστασία των αρθρικών οστικών δομών και στην εξασφάλιση σταθερών λειτουργικών αρθρώσεων, η ανάπτυξη μεθόδων που προάγουν την αναγέννηση ή / και την επιδιορθώση των ιστών αυτών ειναι εξαιρετικά σημαντική. Η επιστήμη της ανάπτυξης μηχανικών ιστών παρέχει σήμερα εξαιρετικές προοπτικές στη θεραπεία των εκφυλισμένων και παθολογικών χόνδρινων ιστών. Και ενώ μεγάλη πρόοδος έχει επιτευχθεί πρόσφατα ως προς την ανάπτυξη νεοχόνδρινων ιστών με θλιπτικές μηχανικές ιδιότητες ανάλογες των φυσικών ιστών, ωστόσο οι ιδιότητες εφελκυσμού των νεοϊστών ειναι συγκριτικά υποδιαίστερες. Ως εκ τούτου, η ανάγκη ανάπτυξης νέων βελτιωμένων μεθόδων για να δημιουργία λειτουργικών νεοϊστών και την αποτελεσματική αντιμετώπιση των περίπου 46.4 εκατομμυρίων ασθένών που υποφέρουν σήμερα από αρθρίτιδα μόνο στις Ηνωμένες Πολιτείες, καθίσταται ιδιαίτερα επιτακτική.Δεδομένης της προόδου που έχει επιτευχθεί την τελευταία δεκαετία στην ανάπτυξη μηχανικών χόνδρινων ιστών, η παρούσα διδακτορική διατριβή έχει τρεις γενικούς στόχους: 1) τη διερεύνηση νέων μοριακών/βιολογικών μεθόδων αναγέννησης του αρθρικού χόνδρου σε in vitro και in vivo πειραματικά μοντέλα χόνδρινων βλαβών και οστεοαρθρίτιδας, 2) την ανάπτυξη ή/και βελτίωση μεθόδων αναγέννησης νεοχόνδρινών ιστών με ευρεία κλινική εφαρμογή, και 3) την ανάπτυξη μεθόδων βιολογικής και μηχανικής ωρίμανσης των νεοϊστών και μεθόδων ενσωμάτωσης τους με το φυσικό ιστό μετά απο μεταμόσχευση. Για την επίτευξη των στόχων αυτών, η παρούσα διατριβή περιγράφει την διερεύνηση νέων εξωγενών βιολογικών παραγόντων για την ανάπτυξη μηχανικών νεοϊστών με δομική οργάνωση ανάλογης των αντίστοιχων φυσικών ιστών. Αρχικά, μελετήθηκε η χρήση του χαλκού και της υδροξυλυσίνης, δύο σημαντικών μεσολαβητών της φυσιολογικής διαδικασίας ανάπτυξης διασταυρώμενων δέσμών κολλαγόνου, για την ενίσχυση της περιεκτικότητας των διασταυρώμενων δεσμών κολλαγόνου στους μηχανικούς ιστούς. Αναλόγως, σε μια διαφορετική μελέτη διερευνήθηκε η in vitro καλλιέργεια φυσικών μυοσκελετικών ιστών και μηχανικών νεοϊστών σε υποξικό περιβάλλον, με στόχο την ενίσχυση της περιεκτικότητάς τους σε διασταυρώμενους δεσμούς κολλαγόνου, και ως εκ τούτου, τη βελτίωση των λειτουργικών τους ιδιοτήτων. Λαμβάνοντας υπόψη την εκταινώς περιγεγραμένη στη βιβλιογραφία θετική συσχέτιση μεταξύ της περιεκτικότητας διασταυρούμενων δεσμών κολλαγόνου και εφελκυστικών μηχανικών ιδιοτήτων των νεοϊστών, μελετήθηκε μία νέα μέθοδος για την αύξηση αυτών των διασταυρούμενων δεσμών κολλαγόνου βασιζόμενη στην εξωγενή χορήγηση του ενζύμου λυσυλική οξειδάση (LOX) κατά τη καλλιέργεια των νεοϊστών, με απώτερο στόχο την περαιτέρω ενισχυση των λειτουργικών τους ιδιοτήτων.Άλλες μελέτες της παρούσας διατριβής επικεντρώνονται στην ανάπτυξη μεθόδων ενίσχυσης της περιεκτικότητας των μηχανικών ιστών σε κολλαγόνο, που όταν συνδυάζονται με τις τεχνικές ενίσχυσης των διασταυρούμενων δεσμών κολλαγόνου θα μπορούσαν να βελτιώσουν περαιτερώ την μηχανική ωρίμανση των νεοϊστών για την αποτελεσματική αποκατάσταση χόνδρινών ελλειμάτων σε πειραματικά μοντέλα αρθρικών παθήσεων. Ειδικότερα, δύο παράγοντες που είναι γνωστοί ρυθμιστές της ενδοκυτταρικής σηματοδότησης του Ca2+ (η διγοξίνη και η τριφωσφορική αδενοσίνη), εξετάστηκαν ως εναλλακτικές μέθοδοι για τη μηχανική βελτίωση των ιστών μέσω αύξησης της περιεκτικότητάς τους σε κολλαγόνο και σε διασταυρούμενους δεσμούς κολλαγόνου. Επιπλέον, ανάλογες μελέτες επικεντρώθηκαν στην βελτίωση μιας θεραπευτικής αγωγής που περιλαμβάνει το βιοφυσικό παράγοντα χονδροϊτινάση-ABC (C-ABC) και τον βιοχημικό παράγοντα αυξητικό παράγοντα μετασχηματισμού -β1 (ΤGF-β1) με στόχο πάλι την ενισχύση τών λειτουργικών ιδιοτήτων των νεοχόνδρινων ιστών. Μια διαφορετική μελέτη εξέτασε την ικανότητα της εμβιομηχανικής διέγερσης με τη μορφή παθητικής αξονικής θλιπτικής φόρτισης να συμβάλλει σε in vitro ανάπτυξη νεοχόνδρινών ιστών με προδιαγεγραμμένο σχήμα/αρχιτεκτονική. Τέλος, μια πρόσθετη μελέτη διερεύνησε την χρήση χονδροκυττάρων απο την ποδοκνημική άρθρωση για την κατασκευή νεοχόνδρινων μοσχευμάτων προοριζόμενων για την βλάβες της ποδοκνημικής άρθρωσης.Καταλεικτικά, η παρούσα διατριβή διερεύνησε τη δυνατότητα ενσωμάτωσης του νεοχόνδρινου με τον φυσικό ιστό μέσω της εξωγενούς χορήγησης του ενζύμου LOX. Μια αρχική μελέτη διερεύνησε τη δυνατότητα του LOX να προώθηση της ενσωμάτωσης μεταξύ του νεοχόνδρου και του φυσικού αρθρικού χόνδρου σε in vitro περιβάλλον καλλιέργειας των ιστών. Ελπιδοφόρα αποτελέσματα αυτής της μέλετης οδήγησαν σε συνδυασμό του ενζύμου LOX με τους παράγοντες C-ABC και ΤGF-β1 με στόχο την ταυτόχρονη ενίσχυση της ωρίμανσης του νεοχόνδρου και τη ενσωμάτωση του με τον φυσικό αρθρικό χόνδρο. Ειδικότερα, ο συνδυασμός των παραγόντων αυτών εφαρμόστηκε πρώτα σε ένα in vitro μοντέλο ενσωμάτωσης των δύο ιστών, και στη συνέχεια σε ένα πειραματικό ζωικό μοντέλο για τη διερεύνηση της ικανότητας του in νίνο περιβάλλοντος να ενισχύσει περαιτέρω της βιολογική αυτή διεργασία.Σε γενικές γραμμές, η σειρά των μελετών που περιγράφονται στην παρούσα διατριβή αντιπροσωπεύουν πρωτοπόρες και δυνητικώς κλινικά εφαρμόσιμες μοριακές μεθόδους για την ενίσχυση των λειτουργικών ιδιοτήτων ενός μεγάλου φάσματος κολλαγόνων ιστών και νεοϊστών. Συγκεκριμένα, ο χαλκός, η ενδογενής παραγώγη του ενζύμου LOX μέσω της καλλιεργειας των ιστών σε υποξίκό περιβάλλον, και η εξωγενή χορήγηση του LOX βελτιώνουν τις μηχανικές ιδιότητες των μηχανικών ιστών αναδεικνύοντας την ικανότητα στόχευσης της αύξησης των διαστραυρούμενων δεσμών κολλαγόνου για την ανάπτυξη βιομιμητικών και μηχανικά ισχυρών νεοχονδρινών ιστών. Εναλλακτικά, η διγοξίνη, η τριφωσφορική αδενοσίνη, ο C-ABC, ο ΤGF -β1, και η στατική εφαρμογή βάρους αποτελουν αποτελεσματικές μεθόδους για την ενίσχυση του κολλαγόνου και την αυξηση των διαστραυρούμενων δεσμών κολλαγόνου στους νεοϊστούς. Τέλος, η εξωγενής χορήγηση του LOX, μονομερώς ή σε συνδυασμό με τους παράγοντες C-ABC και ΤGF -β1, βρέθηκε να προάγει την in vitro και in vivo ωρίμανση των νεοϊστών και την ενσωμάτωση τους με το φυσικό ιστό, αντανακλώντας την πολλά υπόσχόμενη συνδιαστική χρήση των παραγόντων αυτών για την θεραπευτική αντιμετώπιση χόνδρινων βλαβών in νίνο. Συνολικά, οι μελέτες που περιγράφονται στην παρούσα διατριβή αποτελούν μια επισκόπηση διαφορετικών και πολλά υποσχόμενων νέων τεχνολογιών με στόχο 1) την ενίσχυση των μηχανικών ιδιοτήτων των φυσικών ιστών και νεοϊστών, και 2) την ενίσχυση των δυνατοτήτων τους να ενσωματώνονται in vitro, υπογραμμίζοντας τη δυνατότητα για εφαρμογή των τεχνολογιών αυτών στη ανάπτυξη κλινικά λειτουργικών νεοϊστών για την επιδιόρθωση και / ή αντικατάσταση των ιστών που έχουν καταστραφεί από τραυματισμό ή ασθένεια.

scholarly journals Spatiotemporal regulation of endogenous MSCs using a functional injectable hydrogel system for cartilage regeneration

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Yunsheng Dong ◽  
Yufei Liu ◽  
Yuehua Chen ◽  
Xun Sun ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Cartilage Tissue Engineering ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Cartilage Defects ◽  
In Vivo Experiments ◽  
Spatiotemporal Regulation ◽  
Stromal Cell Derived Factor ◽  
Hydrogel System

AbstractHydrogels have been extensively favored as drug and cell carriers for the repair of knee cartilage defects. Recruiting mesenchymal stem cells (MSCs) in situ to the defect region could reduce the risk of contamination during cell delivery, which is a highly promising strategy to enhance cartilage repair. Here, a cell-free cartilage tissue engineering (TE) system was developed by applying an injectable chitosan/silk fibroin hydrogel. The hydrogel system could release first stromal cell-derived factor-1 (SDF-1) and then kartogenin (KGN) in a unique sequential drug release mode, which could spatiotemporally promote the recruitment and chondrogenic differentiation of MSCs. This system showed good performance when formulated with SDF-1 (200 ng/mL) and PLGA microspheres loaded with KGN (10 μΜ). The results showed that the hydrogel had good injectability and a reticular porous structure. The microspheres were distributed uniformly in the hydrogel and permitted the sequential release of SDF-1 and KGN. The results of in vitro experiments showed that the hydrogel system had good cytocompatibility and promoted the migration and differentiation of MSCs into chondrocytes. In vivo experiments on articular cartilage defects in rabbits showed that the cell-free hydrogel system was beneficial for cartilage regeneration. Therefore, the composite hydrogel system shows potential for application in cell-free cartilage TE.

scholarly journals 3D Cartilage Regeneration With Certain Shape and Mechanical Strength Based on Engineered Cartilage Gel and Decalcified Bone Matrix

2021 ◽  
Vol 9 ◽  
Author(s):  
Zheng Ci ◽  
Ying Zhang ◽  
Yahui Wang ◽  
Gaoyang Wu ◽  
Mengjie Hou ◽  
...  
Keyword(s):  
Mechanical Strength ◽  
Bone Matrix ◽  
Cartilage Regeneration ◽  
Cartilage Tissue ◽  
Cartilage Defects ◽  
High Porosity ◽  
Good Biocompatibility ◽  
Engineered Cartilage ◽  
Decalcified Bone Matrix

Scaffold-free cartilage-sheet technology can stably regenerate high-quality cartilage tissue in vivo. However, uncontrolled shape maintenance and mechanical strength greatly hinder its clinical translation. Decalcified bone matrix (DBM) has high porosity, a suitable pore structure, and good biocompatibility, as well as controlled shape and mechanical strength. In this study, cartilage sheet was prepared into engineered cartilage gel (ECG) and combined with DBM to explore the feasibility of regenerating 3D cartilage with controlled shape and mechanical strength. The results indicated that ECG cultured in vitro for 3 days (3 d) and 15 days (15 d) showed good biocompatibility with DBM, and the ECG–DBM constructs successfully regenerated viable 3D cartilage with typical mature cartilage features in both nude mice and autologous goats. Additionally, the regenerated cartilage had comparable mechanical properties to native cartilage and maintained its original shape. To further determine the optimal seeding parameters for ECG, the 3 d ECG regenerated using human chondrocytes was diluted in different concentrations (1:3, 1:2, and 1:1) for seeding and in vivo implantation. The results showed that the regenerated cartilage in the 1:2 group exhibited better shape maintenance and homogeneity than the other groups. The current study established a novel mode of 3D cartilage regeneration based on the design concept of steel (DBM)-reinforced concrete (ECG) and successfully regenerated homogenous and mature 3D cartilage with controlled shape and mechanical strength, which hopefully provides an ideal cartilage graft for the repair of various cartilage defects.

scholarly journals Protocols for Culturing and Imaging a Human Ex Vivo Osteochondral Model for Cartilage Biomanufacturing Applications

Materials ◽  
2019 ◽  
Vol 12 (4) ◽  
pp. 640 ◽  
Author(s):  
Serena Duchi ◽  
Stephanie Doyle ◽  
Timon Eekel ◽  
Cathal D. O’Connell ◽  
Cheryl Augustine ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Cartilage Regeneration ◽  
Light Sheet ◽  
Cartilage Tissue ◽  
Cartilage Defects ◽  
Label Free ◽  
Microscopy Imaging ◽  
Microscopy Technique

Cartilage defects and diseases remain major clinical issues in orthopaedics. Biomanufacturing is now a tangible option for the delivery of bioscaffolds capable of regenerating the deficient cartilage tissue. However, several limitations of in vitro and experimental animal models pose serious challenges to the translation of preclinical findings into clinical practice. Ex vivo models are of great value for translating in vitro tissue engineered approaches into clinically relevant conditions. Our aim is to obtain a viable human osteochondral (OC) model to test hydrogel-based materials for cartilage repair. Here we describe a detailed step-by-step framework for the generation of human OC plugs, their culture in a perfusion device and the processing procedures for histological and advanced microscopy imaging. Our ex vivo OC model fulfils the following requirements: the model is metabolically stable for a relevant culture period of 4 weeks in a perfusion bioreactor, the processing procedures allowed for the analysis of 3 different tissues or materials (cartilage, bone and hydrogel) without compromising their integrity. We determined a protocol and the settings for a non-linear microscopy technique on label free sections. Furthermore, we established a clearing protocol to perform light sheet-based observations on the cartilage layer without the need for tedious and destructive histological procedures. Finally, we showed that our OC system is a clinically relevant in terms of cartilage regeneration potential. In conclusion, this OC model represents a valuable preclinical ex vivo tool for studying cartilage therapies, such as hydrogel-based bioscaffolds, and we envision it will reduce the number of animals needed for in vivo testing.

scholarly journals Physioxia Expanded Bone Marrow Derived Mesenchymal Stem Cells Have Improved Cartilage Repair in an Early Osteoarthritic Focal Defect Model

Biology ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 230
Author(s):  
Girish Pattappa ◽  
Jonas Krueckel ◽  
Ruth Schewior ◽  
Dustin Franke ◽  
Alexander Mench ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cartilage Repair ◽  
Rabbit Model ◽  
Cartilage Regeneration ◽  
Cartilage Defects ◽  
Large Animal ◽  
Large Animal Models ◽  
Early Oa

Focal early osteoarthritis (OA) or degenerative lesions account for 60% of treated cartilage defects each year. The current cell-based regenerative treatments have an increased failure rate for treating degenerative lesions compared to traumatic defects. Mesenchymal stem cells (MSCs) are an alternative cell source for treating early OA defects, due to their greater chondrogenic potential, compared to early OA chondrocytes. Low oxygen tension or physioxia has been shown to enhance MSC chondrogenic matrix content and could improve functional outcomes of regenerative therapies. The present investigation sought to develop a focal early OA animal model to evaluate cartilage regeneration and hypothesized that physioxic MSCs improve in vivo cartilage repair in both, post-trauma and focal early OA defects. Using a rabbit model, a focal defect was created, that developed signs of focal early OA after six weeks. MSCs cultured under physioxia had significantly enhanced in vitro MSC chondrogenic GAG content under hyperoxia with or without the presence of interleukin-1β (IL-1β). In both post-traumatic and focal early OA defect models, physioxic MSC treatment demonstrated a significant improvement in cartilage repair score, compared to hyperoxic MSCs and respective control defects. Future investigations will seek to understand whether these results are replicated in large animal models and the underlying mechanisms involved in in vivo cartilage regeneration.

Hydrogels with tunable modulus regulate chondrocyte microaggregates growth for cartilage repair

2021 ◽  
Author(s):  
Jing Chen ◽  
Peng An ◽  
Hua Zhang ◽  
Yansheng Zhang ◽  
Hua Wei ◽  
...  
Keyword(s):  
Loss Modulus ◽  
Femoral Condyle ◽  
Cartilage Regeneration ◽  
Cartilage Defects ◽  
High Viability ◽  
Chondrogenic Phenotype ◽  
A Cell ◽  
Weak Gel

Abstract Chondrocyte spheroids in 3D hydrogel are more beneficial to improve their survival and maintain chondrogenic phenotype comparing to dissociated chondrocytes. However, in-situ inducing cell into spheroids rather than encapsulating spheroids in a hydrogel remains a tremendous challenge because of the limitations of biochemical and viscoelastic controllability for hydrogel. Herein, a hydrogel consisting of photo-crosslinkable chitosan methacrylate (CHMA) and semi-interpenetrating polyvinyl alcohol (PVA) is developed as a cell-responsive matrix with controllable viscoelastic properties. The proposed CHMA-PVA precursor preferentially exhibits a weak gel-like state with a storage modulus of 16.9 Pa, loss modulus of 13.0 Pa and yielding stain of 1%, which could allow chondrocyte to vigorously move and assemble but hinder their precipitation before crosslinking. The chondrocytes could form microaggregates within 8 h in vitro and keep high viability. Moreover, subcutaneous implantation experiments demonstrate that the CHMA/PVA hydrogels are biocompatible and degrade within five weeks in vivo. The cell-free hydrogels are further placed in cylindrical cartilage defects in the rabbit femoral condyle and examined 8 weeks postoperatively. Gross, histological and immunohistochemical analyses reveal a significant acceleration for the cartilage regeneration. These findings suggest that this novel cell adhesion-responsive and histo-compatible hydrogel is promising for cartilage regeneration.

Are Stem Cells Useful in the Regeneration and Repair of Cartilage Defects in the TMJ Condyle? An In Vivo Study

2021 ◽  
Vol 7 (2) ◽  
Author(s):  
Guastaldi FPS ◽  
◽  
Hakim MA ◽  
Liapaki A ◽  
Lowe B ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cartilage Defect ◽  
Cartilage Regeneration ◽  
Cartilage Defects ◽  
Control Group ◽  
Condylar Cartilage ◽  
Group Data ◽  
Group Control Group ◽  
Safranin O

Temporomandibular Joint (TMJ) disorders affect up to 10-40% of the population and if left untreated, may eventually lead to Osteoarthritis (OA) of the TMJ. In vivo TMJ repair and regeneration has received significant attention and represents a promising approach for the treatment of degenerative TMJ disorders. The aim of this study was to present a pre-clinical mouse model of TMJ articular cartilage defect and evaluate the utility of a potential tissue engineered TMJ therapy utilizing Mesenchymal Stem Cells (MSCs) derived from mice condyle, hydrogel, and biosilica. C57BL/6 mice (n=30) were equally divided into the following groups: sham group (S-group); control group, condylar cartilage defect only (CD-group); experimental group, condylar cartilage defect + direct administration of MSCs+hydrogel+biosilica (H-group). Mice were euthanized at 4 (n=15) and 8 (n=15) weeks and TMJ joint specimens were harvested for analysis. H&E and Safranin O stained sections showed intact articular surfaces on the condyle and glenoid fossa at both time points, maturation and distribution of chondrocytes along the condyle for the H-group compared to the CD-group. Data from this preliminary study shows that MSCs+hydrogel+biosilica may represent an experimental therapeutic compound for TMJ condylar cartilage regeneration.

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