Treatment Of Cartilage Injuries Research Articles

Cartilage-Inspired, High-Strength, and Heat-Tolerant Lubricating Hydrogels by Macrophase Separation.

Hydrogels are considered as a potential cartilage replacement material based on their structure being similar to natural cartilage, which are of great significance in repairing cartilage defects. However, it is difficult for the existing hydrogels to combine the high load bearing and low friction properties (37 °C) of cartilage through sample methods. Herein, we report a facile and new fabrication strategy to construct the PNIPAm/EYL hydrogel by using the macrophase separation of supersaturated N-isopropylacrylamide (NIPAm) monomer solution to promote the formation of liposomes from egg yolk lecithin (EYL) and asymmetric template method. The PNIPAm/EYL hydrogels possess a relatively high compressive strength (more than 12 MPa), fracture energy (9820 J/m2), good fatigue resistance, lubricating properties, and excellent biocompatibility. Compared with the PNIPAm hydrogel, the friction coefficient (COF 0.046) of PNIPAm/EYL hydrogel is reduced by 50%. More importantly, the COF (0.056) of PNIPAm/EYL hydrogel above lower critical solution temperature (LCST) does not increase significantly, exhibiting heat-tolerant lubricity. The finite element analysis further proves that PNIPAm/EYL hydrogel can effectively disperse the applied stress and dissipate energy under load conditions. This work not only provides new insights for the design of high-strength lubricating hydrogels but also lays a foundation for the treatment of cartilage injury as a substitute material.

The current status and future prospects of mesenchymal stem cell transplantation for the treatment of knee articular cartilage injuries and osteoarthritis

The prevalence of articular cartilage injuries and osteoarthritis (OA) is high, affecting a wide range of individuals. The self-repair ability of cartilage tissue is poor, and once damaged, it will irreversibly progress to OA. Mesenchymal stem cells (MSCs) play an important role in the field of regenerative medicine and are considered one of the most promising seed cells for cartilage repair and regeneration. In this article, based on the latest clinical research findings from both domestic and international sources, the theoretical basis, treatment goals, significance, sources, characteristics, clinical implementation plans, and efficacy of using MSCs for the treatment of cartilage injuries or osteoarthritis are reviewed. The article also discusses the challenges faced and future directions that need to be addressed in the clinical application of MSCs.

Effect of novel composite materials on human injury and rehabilitation training in athletic long jump sports

Articular cartilage injuries are prevalent in track and field long jump and can affect an athlete’s health. However, current therapeutic options cannot effectively repair the damaged cartilage tissue. It is important to find alternative treatment methods that can provide better results for injured athletes. In this study, carbon nanofibers (CNFs) were employed to enhance the properties of hyaluronic acid (HA) and develop nanocomposite hydrogel scaffolds. Bone marrow mesenchymal stem cells extracted from the joints of experimental mice were subsequently loaded onto the CNFs-HA scaffolds and evaluated for bioactivity and repair capacity. The TEM photographs of CNFs-MA displayed an orderly arrangement of fibers. Observing the FT-IR spectral characteristics of CNFs-MA revealed a telescopic vibration peak at 1700 cm−1. CNFs-HA demonstrated a rapid increase in cartilage damage repair score after 15 days, and at 1 month, the joint damage repair score of CNFs-HA was significantly different from that of pure HA and the untreated group. Based on the foregoing results, it can be inferred that CNFs-HA, as prepared, is biocompatible and efficacious in treating articular cartilage tissue injury. Furthermore, this study this study provides a reliable solution for cartilage injury treatment and establishes an experimental basis for its clinical management.

Knee Cartilage Injuries in Football Players: Clinical Outcomes and Return to Sport After Surgical Treatment: A Systematic Review of the Literature.

To systematically review the literature and analyze clinical outcomes and return-to-sport after surgical management of cartilage injuries in football players. A systematic literature review was performed in August 2023 on PubMed, WebOfScience, and Cochrane Library to collect studies on surgical strategies for cartilage lesions in football players. Methodological quality and risk of bias were assessed with the modified Coleman Methodology score and RoB2 and RoBANS2 tools. Fifteen studies on 409 football players (86% men, 14% women) were included: nine prospective and two retrospective case series, one randomized controlled trial, one prospective comparative study, one case report, and one survey. Bone marrow stimulation (BMS) techniques were the most documented. The lesion size influenced the treatment choice: debridement was used for small lesions (1.1 cm2), BMS, osteochondral autograft transplantation (OAT), matrix-assisted autologous chondrocytes transplantation (MACT), and scaffold-augmented BMS for small/mid-size lesions (2.2-3.0 cm2), and autologous chondrocytes implantation (ACI) for larger lesions (5.8 cm2). The surgical options yielded different results in terms of clinical outcome and return-to-sport, with fastest recovery for debridement and scaffold-augmented BMS. The current evidence is limited with large methodological quality variation (modified Coleman Methodology score 43.5/100) and a high risk of bias. Decision-making in cartilage injuries seems to privilege early return-to-sport, making debridement and microfractures the most used techniques. The lesion size influences the treatment choice. However, the current evidence is limited. Further studies are needed to confirm these findings and establish a case-based approach to treat cartilage injuries in football players based on the specific patient and lesion characteristics and the treatments' potential in terms of both return-to-sport and long-term results. Systematic review, level IV.

Nature‐Inspired Strategies for the Treatment of Osteoarthritis

AbstractArticular cartilage is devoid of nerves and blood vessels, and its nutrients must be obtained from the joint fluid; therefore, its ability to repair itself is limited. Manufactured materials such as artificial cartilage or synthetic materials are typically used in traditional approaches for knee cartilage repair. However, durability, postimplant rejection, and tissue incompatibility are the problems associated with these materials. In recent decades, tissue engineering and regenerative medicine have focused on the development of functional substitutes, particularly those based on naturally inspired biopolymers. This review focuses on sustainably produced biopolymers based on materials derived from natural sources. Furthermore, these materials have many advantages, including low antigenicity, biocompatibility, and degradability. Of course, there are also many challenges associated with natural materials, such as the lack of clinical studies and long‐term follow‐up data, unstable mechanical properties of the materials, and high demands placed on preparation and molding techniques. In this review, an overview of natural and nature‐inspired polymers that are the subject of research to date, as well as their structural designs and product performances is provided. This review provides scientific guidance for enhancing the development of naturally inspired materials for treating cartilage injuries.

Glucosamine-loaded injectable hydrogel promotes autophagy and inhibits apoptosis after cartilage injury

The ability of cartilage to regenerate and repair is limited. N-acetyl- d-glucosamine (GlcNAc) is a nutritional supplement commonly used to activate chondrocytes. To prolong the duration of action of GlcNAc and improve its curative effect after cartilage injury, a GlcNAc thermosensitive hydrogel is prepared based on Pluronic F127 (PF127). The physicochemical properties results indicate that this hydrogel is injectable and retards the release of GlcNAc. Further, the therapeutic benefits of GlcNAc hydrogel are detected through intra-articular injection in rat specimens with cartilage injury. Behavioral experiments results indicate that the rats treated with GlcNAc hydrogel had longer step lengths, smaller foot angles and slower fall times. Compared with the sham group, the expression of Sox9 was 1.5 times and the level of collagen II was 2.4 times in the hydrogel treated group. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining result confirmed that the GlcNAc hydrogel reduce apoptosis by about 50%. Our results of immunohistochemical staining, Western blotting assays and enzyme activity detection all suggested that GlcNAc hydrogel reduce the expression of cleaved-caspase3 and caspase8 (Compared to the sham group, the protein contents were reduced by about 50% in the GlcNAc hydrogel group). We also found that GlcNAc hydrogel activates autophagy through ERK signal pathway. The results of Western blotting indicated that GlcNAc hydrogel increase the levels of LC3B and Becline1 (hydrogel group & sham group, LC3B: 1.56 ± 0.07 & 1.00 ± 0.14; Becline1: 1.98 ± 0.07 & 1.00 ± 0.13). Whereas, the content of P62 reduced after GlcNAc hydrogel treatment, the relative level in sham group and hydrogel group are 1.00 ± 0.02 and 0.73 ± 0.06. Our results revealed that the number of P-ERK positive cells in the hydrogel group (57.36 ± 3.56%) was higher when compared with the sham (24.82 ± 2.72%). And, the ratio of P-ERK and ERK was higher than that in the sham group (1.48 ± 0.07 & 1.00 ± 0.08). The GlcNAc thermosensitive hydrogel is a promising and sustainable drug delivery system for intra-articular injection in the treatment of cartilage injury.

Biomimetic approach for an articular cartilage patch: Combination of decellularized cartilage matrix and silk-elastin-like-protein (SELP) hydrogel

Articular cartilage degradation due to injury, disease and aging is a common clinical issue as current regenerative therapies are unable to fully replicate the complex microenvironment of the native tissue which, being avascular, is featured by very low ability to self-regenerate. The extracellular matrix (ECM), constituting almost 90% of the entire tissue, plays a critical role in its function and resistance to compressive forces. In this context, the current tissue engineering strategies are only partially effective in restoring the biology and function of the native tissue. A main issue in tissue regeneration is treatment failure due to scarce integration of the engineered construct, often following a gradual detachment of the graft. In this scenario, we aimed to create an adhesive patch able to adequately support cartilage regeneration as a promising tool for the treatment of cartilage injuries and diseases. For this, we produced an engineered construct composed of decellularized ECM (dECM) obtained from horse joint cartilage, to support tissue regeneration, coupled with a Silk-Elastin-Like Proteins (SELP) hydrogel, which acts as a biological glue, to guarantee an adequate adherence to the host tissue. Following the production of the two biomaterials we characterized them by assessing: 1) dECM morphological, chemical, and ultrastructural features along with its capability to support chondrocyte proliferation, specific marker expression and ECM synthesis; 2) SELP microarchitecture, cytocompatibility and mechanical properties. Our results demonstrated that both materials hold unique properties suitable to be exploited to produce a tailored microenvironment to support cell growth and differentiation providing a proof of concept concerning the in vitro biological and mechanical efficacy of the construct. The SELP hydrogel displayed a very interesting physical behavior due to its high degree of resistance to mechanical stress, which is generally associated with physiological mechanical load during locomotion. Intriguingly, the shear-thinning behavior of the hydrogel may also make it suitable to be applied and spread over non-homogeneous surfaces, therefore, we hypothesize that the hybrid biomaterial proposed may be a real asset in the treatment of cartilage defects and injuries.

Mesenchymal progenitor cells from non-inflamed versus inflamed synovium post-ACL injury present with distinct phenotypes and cartilage regeneration capacity

BackgroundOsteoarthritis (OA) is a chronic debilitating disease impacting a significant percentage of the global population. While there are numerous surgical and non-invasive interventions that can postpone joint replacement, there are no current treatments which can reverse the joint damage occurring during the pathogenesis of the disease. While many groups are investigating the use of stem cell therapies in the treatment of OA, we still don’t have a clear understanding of the role of these cells in the body, including heterogeneity of tissue resident adult mesenchymal progenitor cells (MPCs).MethodsIn the current study, we examined MPCs from the synovium and individuals with or without a traumatic knee joint injury and explored the chondrogenic differentiation capacity of these MPCs in vitro and in vivo.ResultsWe found that there is heterogeneity of MPCs with the adult synovium and distinct sub-populations of MPCs and the abundancy of these sub-populations change with joint injury. Furthermore, only some of these sub-populations have the ability to effect cartilage repair in vivo. Using an unbiased proteomics approach, we were able to identify cell surface markers that identify this pro-chondrogenic MPC population in normal and injured joints, specifically CD82LowCD59+ synovial MPCs have robust cartilage regenerative properties in vivo.ConclusionsThe results of this study clearly show that cells within the adult human joint can impact cartilage repair and that these sub-populations exist within joints that have undergone a traumatic joint injury. Therefore, these populations can be exploited for the treatment of cartilage injuries and OA in future clinical trials.

Hyalofast Cartilage Repair Surgery with a Full Load-Bearing Rehabilitation Program One Day after Operation Reduces the Time for Professional Athletes to Return to Play.

Background and Objectives: This study evaluated the effectiveness of Hyalofast cartilage repair surgery with an early, full load-bearing rehabilitation program one day after the operation for reducing the time needed for professional athletes to return to play. Materials and Methods: This prospective study included 49 patients aged between 19 and 38 years who had undergone surgical reconstruction of cartilage using the microfracture technique combined with a Hyalofast scaffold. All patients were active professional athletes. Early rehabilitation was implemented from the first postoperative day, fully loading the operated limb. A clinical evaluation was based on the KOOS and SF-36 questionnaires used during subsequent follow-up visits. All patients underwent magnetic resonance imaging (MRI) to evaluate the effect of the surgery after one year. Results: The clinical results demonstrated a statistically significant improvement in the number of complaints about pain and in the quality of life of the patients, measured in all of the applied scales, with comparisons made between six months or one year post-surgery and pre-surgery. Importantly for athletes, the parameter related to sports and recreation improved from 14 ± 11.1 to 95 ± 7.7 6 months after surgery and to 99.8 ± 1.8 one year after surgery. The overall quality of life score improved from 30 ± 18 to 88 ± 8.8 one year after surgery. Conclusions: These results show that this approach significantly shortened the time needed for the athletes to return to sports at the same level as before the surgery (athletes returned to sports in approximately 2.5-3 months). The mean follow-up time was 19.75 months. This technique can be considered a viable option for the treatment of cartilage injuries in professional athletes, allowing them to return to play more quickly in a safe and healthy way.

Rethinking Cartilage Lesions of the Ankle: An Update on the Role of Biologic Adjuvants.

Osteochondral lesions of the talus are common injuries in the ankle joint often resulting in early-onset osteoarthritis if left untreated. The avascular nature of articular cartilage limits healing capacity; therefore, surgical strategies are typically used in the treatment of these injuries. These treatments often result in the production of fibrocartilage rather than the native hyaline cartilage, which has decreased mechanical and tribological properties. Strategies to improve the ability of fibrocartilage to be more hyaline-like and thus more mechanically robust have been widely investigated. Biologic augmentation, including concentrated bone marrow aspirate, platelet-rich plasma, hyaluronic acid, and micronized adipose tissue, has been used in the augmentation of cartilage healing, with studies demonstrating promise. This article provides an overview and update on the various biologic adjuvants used in the treatment of cartilage injuries in the ankle joint.

Repair of Rabbit Knee Cartilage by Bipolar Radiofrequency with Different Energy Settings and Recovery Periods.

Arthroscopic bipolar radiofrequency energy (bRFE) is a common method for minimally invasive treatment of cartilage injuries. The benefits of bRFE are still controversial, and its safety has become the focus of attention. This study aimed to reveal the effects of energy setting and recovery period on the efficacy and safety of bRFE. The New Zealand white rabbit knee cartilage injury model was established, and bRFE was used to treat the cartilage with different energy settings, including 20 W and 40 W, and recovery periods of 0 and 1 month. By observing the immediate and late results on damaged cartilage, along with chondrocyte apoptosis, the effects of energy setting and recovery period on the efficacy and safety of bRFE were accessed. The pathological conditions, surface profile and chondrocyte viability in the bRFE treatment group produced greater late effects and were significantly better than those in the model group. Nevertheless, bRFE produced a timely injury that resulted in an increased rate of apoptosis (p < 0.05), which was alleviated in subsequent recovery (p < 0.05). bRFE can effectively trim and improve the cartilage lesion area, and reduce cracks. Although bRFE produced timely chondrocyte damage, this was alleviated on subsequent recovery. Therefore, bRFE with appropriate energy is beneficial to the recovery of cartilage damage, proper attention should be paid to the recovery period.

Current problems and persprectives of the treatment of cartilage injuries using mesenchimal stem cells

Annotation. Since standard methods of treatment of cartilage trauma and inflammatory diseases lack effectiveness, at present one of the most promising strategies is mesenchymal stem cell transplantation. Despite the successes in this field, many issues, such as the selection of the tissue-source of mesenchymal stem cells (MSCs) and their optimization or modification in culture in order to achieve the maximum therapeutic effect, remains an actual task for both global and domestic scientists. The purpose of the study is to prepare a review of literature sources for the period 2004-2022 (in the vast majority on publications of the last five years) and to systematize new data on the biological characteristics of MSCs from various tissue sources, which are used in strategies for the treatment of cartilage lesions tissues, to analyze existing problems and further prospects, as well as potential ways of optimizing MSC cultivation methods to increase their regenerative potential. A study of 49 sources that met the inclusion criteria was carried out. A significant variety of strategies for the use of MSCs in animal models and in clinical practice was revealed. The main mechanisms ensuring the therapeutic effect of MSCs have been determined and can be used as criteria for optimizing cellular material. However, it was found that the question of the effectiveness of the use of differentiated MSCs, the selection of the tissue-source of MSCs, and the specifics of the use of MSCs from neonatal sources remains open. Thus, the analysis of literary sources revealed further promising ways to improve the therapeutic efficiency of MSC grafting in a wide range of cartilaginous lesions. There is a need to research the effects of MSCs from neonatal tissues, and especially the umbilical cord. This will become possible due to experimental research that will be carried out in the future.

Hypoxia-mimicking scaffolds with controlled release of DMOG and PTHrP to promote cartilage regeneration via the HIF-1α/YAP signaling pathway

Efficiently driving chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) while avoiding undesired hypertrophy remains a challenge in the field of cartilage tissue engineering. Here, we report the sequential combined application of dimethyloxalylglycine (DMOG) and parathyroid hormone-related protein (PTHrP) to facilitate chondrogenesis and prevent hypertrophy. To support their delivery, poly(lactic-co-glycolic acid) (PLGA) microspheres were fabricated using a double emulsion method. Subsequently, these microspheres were incorporated onto a poly(l-lactic acid) (PLLA) scaffold with a highly porous structure, high interconnectivity and collagen-like nanofiber architecture to construct a microsphere-based scaffold delivery system. These functional constructs demonstrated that the spatiotemporally controlled release of DMOG and PTHrP effectively mimicked the hypoxic microenvironment to promote chondrogenic differentiation with phenotypic stability in a 3D culture system, which had a certain correlation with the interaction between hypoxia-inducible Factor 1 alpha (HIF-1α) and yes-associated protein (YAP). Subcutaneous implantation in nude mice revealed that the constructs were able to maintain cartilage formation in vivo at 4 and 8 weeks. Overall, this study indicated that DMOG and PTHrP controlled-release PLGA microspheres incorporated with PLLA nanofibrous scaffolds provided an advantageous 3D hypoxic microenvironment for efficacious and clinically relevant cartilage regeneration and is a promising treatment for cartilage injury.

Sericin-reinforced dual-crosslinked hydrogel for cartilage defect repair

Articular cartilage is essential for normal daily joint function activities. However, it is difficult for articular cartilage to repair itself after injury due to the lack of nerves and blood vessels, so an effective cartilage repair method is necessary. As a three-dimensional polymer network structure with high water content, hydrogel is a good candidate material for cartilage repair, and it is also a research hotspot in the treatment of cartilage injury. Here, a porous dual-crosslinked hydrogel containing sodium alginate (SA) and silk sericin (SS) was designed for in situ repair of cartilage damage. The degradation rate of the hydrogel was regulated by changing the content of SS to match the rate of cartilage regeneration. The hydrogel had excellent mechanical properties (compressive strength≈245 kPa, compressibility≈60%), high water content (85%−88%) and porosity(>20%), and when the content of SS is 1%, the scaffold has the best comprehensive performance. Existing excellent cytocompatibility, the scaffold can promote the adhesion and proliferation of chondrocytes while reducing inflammatory cell infiltration. The cartilage defect repair experiments in vivo showed that artificial cartilage was formed at 4 weeks with molecular structure similar to natural cartilage. It is expected to be applied to clinical cartilage repair through the dual-crosslinked three-dimensional cartilage scaffold.

Biomimetic injectable hydrogel based on silk fibroin/hyaluronic acid embedded with methylprednisolone for cartilage regeneration

Articular cartilage injury is characterized by limited self-repair capacity due to the shortage of blood vessels, lymphatics, and nerves. Hence, this study aims to exploit a classic injectable hydrogel platform that can restore the cartilage defects with minimally invasive surgery, which is similar to the natural extracellular microenvironment, and highly porous network for cell adhesion and proliferation. In this study, an injectable scaffold system comprised of silk fibroin (SF) and hyaluronic acid (HA) was developed to adapt the above requirements. Besides, methylprednisolone (MP) was encapsulated by SF/HA scaffold for alleviating inflammation. The SF/HA hydrogel scaffold was prepared by chemical cross-linking between the lysine residues of SF via Schiff base formation, and pore diameter of the obtained hydrogels was 100.47 ± 32.09 µm. The highly porous nature of hydrogel could further benefit the soft tissue regeneration. Compared with HA-free hydrogels, SF/HA hydrogel showed more controlled release on MP. In ovo experiment of chick embryo chorioallantoic membrane (CAM) demonstrated that SF/HA hydrogels not altered the angiogenesis and formation of blood vessels, thus making it suitable for cartilage regeneration. Furthermore, in vivo gel formation was validated in mice model, suggesting in situ gel formation of SF/HA hydrogels. More importantly, SF/HA hydrogels exhibited the controlled biodegradation. Overall, SF/HA hydrogels provide further insights to the preparation of effective scaffold for tissue regeneration and pave the way to improve the articular cartilage injury treatment.

Dynamic protein hydrogel with supramolecularly enveloped kartogenin promotes cartilage regeneration through mitochondrial activation

Limited self-renewal potency of cartilage impedes the repair and regeneration at the site of damage. Investigating small-molecule compounds to boost chondrogenesis has yielded the dawn. However, the durability and targeting of current drug delivery and the adaptive integration for cartilage defects are not addressed. Herein, we fabricated a dynamic hydrogel based on the coordination between metal ions and collagen and then supramolecularly enveloped with a chondro-inductive factor kartogenin (KGN) via cyclodextrin (CD). The self-recovery and injectability of dynamic hydrogel enabled minimally invasive and precise treatment of cartilage injury assisted by continuous KGN administration. The hydrogel could significantly promote the expression of cartilage matrix components (type II collagen and aggrecan) in articular chondrocytes without affecting cell proliferation or migration in vitro. Mechanistically, the protective effects depended on enhancing chondrocyte mitochondrial function and intracellular antioxidant properties. In situ hydrogel injection strengthened cartilage regenerative potential and facilitated the reconstruction of subchondral bone following full-thickness defects in vivo. This study revealed that the dynamic chondrogenic hydrogel could benefit cartilage repair via mitochondrial reinforcement, acting as a novel therapeutic strategy for refractory cartilage damage.

Peripheral Blood-Derived Stem Cells for the Treatment of Cartilage Injuries: A Systematic Review

Background: The treatment of cartilage damage is a hot topic at present, and cell therapy is an emerging alternative therapy. Stem cells derived from peripheral blood have become the focus of current research due to the ease of obtaining materials and a wide range of sources. Methods: We used a text search strategy using the [“mesenchymal stem cells” (MeSH term) OR “MSC” OR “BMMSC” OR “PBMSC” OR” PBMNC” OR “peripheral blood stem cells”] AND (cartilage injury [MeSH term] OR “cartilage” OR “chondral lesion”). After searching the literature, through the inclusion and exclusion criteria, the last included articles were systematically reviewed. Result: We found that peripheral blood-derived stem cells have chondrogenic differentiation ability and can induce chondrogenic differentiation and repair in vivo and have statistical significance in clinical and imaging prognosis. It is an improvement of academic differences. Compared with the bone marrow, peripheral blood is easier to obtain, widely sourced, and simple to obtain. In the future, peripheral blood will be a more potential cell source for cell therapy in the treatment of cartilage damage. Conclusion: Stem cells derived from peripheral blood can repair cartilage and are an important resource for the treatment of cartilage damage in the future. The specific mechanism and way of repairing cartilage need further study.

Paper 40: Improved Cartilage Healing with Microfracture Augmented with Fisetin &amp; Bone Marrow Aspirate Concentrate in Acute Osteochondral Defect

Paper 40: Improved Cartilage Healing with Microfracture Augmented with Fisetin &amp; Bone Marrow Aspirate Concentrate in Acute Osteochondral Defect

3D-Printed Porous Scaffolds of Hydrogels Modified with TGF-β1 Binding Peptides to Promote In Vivo Cartilage Regeneration and Animal Gait Restoration.

The treatment of cartilage injury and osteoarthritis has been a classic problem for many years. The idea of in situ tissue regeneration paves a way for osteochondral repair in vivo. Herein, a hydrogel scaffold linked with bioactive peptides that can selectively adsorb transforming growth factor β1 (TGF-β1) was hypothesized to not only afford cell ingrowth space but also induce the endogenous TGF-β1 recruitment for chondrogenesis promotion. In this study, bilayered porous scaffolds with gelatin methacryloyl (GelMA) hydrogels as a matrix were constructed via three-dimensional (3D) printing, of which the upper layer was covalently bound with bioactive peptides that can adsorb TGF-β1 for cartilage repair and the lower layer was blended with hydroxyapatite for subchondral regeneration. The scaffolds showed promising therapeutic efficacy proved by cartilage and osteogenic induction in vitro and osteochondral repair of rats in vivo. In particular, the animal gait behavior was recovered after the in situ tissue regeneration, and the corresponding gait analysis demonstrated the promotion of tissue regeneration induced by the porous hydrogels with the binding peptides.

Tissue Engineering and Cell Therapy for Cartilage Repair: Preclinical Evaluation Methods.

A chondral injury is a limiting disease that can affect the quality of life and be an economic burden due to the cost of immediate treatment and loss in work productivity. If left untreated, such an injury may progress to osteoarthritis, a degenerative and debilitating joint disease characterized by pain and functional impairment. Mesenchymal stromal cells (MSCs), which have immune-modulatory properties and the ability to differentiate into chondroblasts and osteoblasts, are a predictable source for the treatment of cartilage injuries. This article presents tools to evaluate cartilage restoration by tissue engineering and cell therapy treatment in a translational and preclinical large animal model. In this controlled experimental study with 14 miniature pigs, a scaffold-free tissue engineering construct (TEC) derived from dental pulp and synovial MSCs for cartilage therapy was tested. Total thickness cartilage defects were performed in both posterior knees. The defect was left empty in one of the knees, and the other received the TEC. The tissue repair was morphologically assessed by magnetic resonance imaging (MRI) using the three-dimensional double echo steady-state (3D-DESS) sequence, and compositional assessment was carried out based on the T2 mapping technique. The osteochondral specimens were fixed for histopathology, decalcified, subjected to standard histological processing, sectioned, and stained with hematoxylin and eosin. The sections stained for immunohistochemical detection of collagen types were digested with pepsin and chondroitinase and incubated with antibodies against them. The mechanical evaluation involved analysis of Young's modulus of the cartilage samples based on the indentation and maximum compression test. In addition, a finite element model was used to simulate and characterize properties of the osteochondral block. At 6 months after surgery, there were no complications with the animals and the MRI, histological, immunohistochemical, and biomechanical evaluations proved to be effective and qualified to differentiate good quality chondral repair from inadequate repair tissue. The proposed methods were feasible and capable to properly evaluate the defect filled with TEC containing stromal cells after 6 months of follow-up in a large animal model for articular cartilage restoration. Impact Statement Articular chondral injuries are prevalent and represent an economic burden due to the cost of treatment. The engineering of cartilage tissue can promote the repair of chondral injuries and is dependent on selecting appropriate cells and biocompatible frameworks. In this article, methods for evaluation of a scaffold-free cell delivery system made from mesenchymal stromal cells were present in a translational study that allows further clinical safety and efficacy trials.