Cartilage lesions can progress into secondary osteoarthritis and cause severe clinical problems in numerous patients. As a prospective treatment of such lesions, human-derived induced pluripotent stem cells (iPSCs) were shown to be 3D bioprinted into cartilage mimics using a nanofibrillated cellulose (NFC) composite bioink when co-printed with irradiated human chondrocytes. Two bioinks were investigated: NFC with alginate (NFC/A) or hyaluronic acid (NFC/HA). Low proliferation and phenotypic changes away from pluripotency were seen in the case of NFC/HA. However, in the case of the 3D-bioprinted NFC/A (60/40, dry weight % ratio) constructs, pluripotency was initially maintained, and after five weeks, hyaline-like cartilaginous tissue with collagen type II expression and lacking tumorigenic Oct4 expression was observed in 3D -bioprinted NFC/A (60/40, dry weight % relation) constructs. Moreover, a marked increase in cell number within the cartilaginous tissue was detected by 2-photon fluorescence microscopy, indicating the importance of high cell densities in the pursuit of achieving good survival after printing. We conclude that NFC/A bioink is suitable for bioprinting iPSCs to support cartilage production in co-cultures with irradiated chondrocytes.

Human embryonic stem cells (hESCs) have great potential for the repair of damaged articular cartilage. We developed a serum-free 14-day protocol for hESC differentiation into chondrocyte progenitors, which surprisingly lacked strong cartilage matrix production in in vitro tests. In order to direct these progenitors to a more mature phenotype, we investigated substituting different members of the TGFβ family in the protocol. Initially, we supplemented, or substituted GDF5 (day 11–14), with combinations of BMP7 and TGFβ-1, or −3, but these modifications yielded no improvement in matrix gene expression. However, replacing BMP4 with BMP2 (days 3–10 of the protocol) resulted in a more rapid increase in SOX9 gene expression and increased expression of chondrogenic genes SOX5, ACAN and COL2A1. The replacement of BMP4 with BMP2 also enhanced the formation of chondrogenic cell aggregates, with greater deposition of type II collagen. This change was not accompanied by hypertrophic chondrocyte marker COL10A1 expression. The results demonstrate that BMP2 has greater specificity for the generation of chondrogenic cells from hESCs than BMP4 and this was consistent in two hESC lines (HUES1 and MAN7). hESC-chondrogenic cells derived with either BMP2 or BMP4 were tested in vivo by implanting them in fibrin into osteochondral defects in the femur of RNU rats. Repaired cartilage tissue, positive for Safranin O and type II collagen was detected at 6 and 12 weeks with both cell sources, but the BMP2 cells scored higher for tissue quality (Pineda score). Therefore, BMP2 is more effective at driving chondrogenic differentiation from human pluripotent stem cells than BMP4 and the effect on the resulting chondroprogenitors is sustained in an in vivo setting.

BackgroundAutologous chondrocyte transplantation is a promising technique for treatment of cartilage defects. Three dimensional chondrocyte cultures on a scaffold are widely used to retain the chondrogenic phenotype. Using a biodegradable gelatin scaffold is one option for the cell delivery system, but molecular and histological studies of the method have not yet been done.MethodsWe evaluated the chondrogenic property of the primary human chondrocyte on a gelatin scaffold as compared to a collagen scaffold over a period of 21 days. We examined the production of glycosaminoglycan by quantitative and histological analysis. Gene expression of cartilage-associated molecules was assessed by quantitative RT-PCR.ResultsThe gelatin scaffold showed the ability to promote chondrocyte expansion, chondrogenic phenotype retention at molecular and mRNA levels.ConclusionsThis scaffold is thus suitable for use as an in vitro model for chondrocyte 3D culture.

Background: The process of returning to work after cartilage treatment has not been studied in depth, even though a better understanding of potential outcomes could lead to significant benefits for the general population. Purpose: To determine which surgical interventions are most effective in helping patients return to work after cartilage repair and to identify factors that affect the ability to return to work. Study Design: Systematic review; Level of evidence, 4. Methods: This systematic review followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines in analyzing reports on articular cartilage treatment and return to work published from January 1966 (when the first system of classifying articular cartilage injuries based on the mechanism of injuries and type of lesions was developed) to January 2019. General surgical information and available clinical scores were used to assess outcomes. Results: Only 5 studies describing 283 patients were found to be relevant to our objectives and were therefore included in the analysis. Autologous chondrocyte implantation (ACI) and osteochondral allografts were the only 2 procedures for which information was included regarding patient return to work rates. The mean (overall) return-to-work time after a cartilage repair operation was 4.80 ± 3.02 months. ACI was the most common procedure (3 studies; 227 patients). Return to work after ACI or ACI with high tibial osteotomy (HTO) occurred in almost 100% of cases, whereas the rate of return to work was 51.78% for patients who underwent osteochondral allograft ( P < .01); further, patients who had ACI or ACI+HTO returned to work sooner compared with patients who underwent osteochondral allograft. The Knee injury and Osteoarthritis Outcome Score (KOOS) and Single Assessment Numerical Evaluation (SANE) scores were significantly higher in patients who fully returned to work. No significant difference was found in rates of return to work after ACI related to sex, area of the lesion, or size of the defect. Conclusion: The vast majority of published results on articular cartilage repair do not include data on return to work. Although available data on articular cartilage repair in the general population reveal a high rate of return to work, including those patients treated with ACI, the data do not stratify patients by the type and demand of work. No randomized studies have examined return-to-work rates. Hence, authors should include these data in future studies. A refined definition of work intensity, rather than just return to work, may provide a clearer picture of the relative effectiveness of different surgical interventions. To that end, the authors propose a return to work prognostic score called the Prognostic Cartilage Repair Return to Work Score, or PROCART-RTW score.