Gelatin Microsphere for Cartilage Tissue Engineering: Current and Future Strategies

The gelatin microsphere (GM) provides an attractive option for tissue engineering due to its versatility, as reported by various studies. This review presents the history, characteristics of, and the multiple approaches to, the production of GM, and in particular, the water in oil emulsification technique. Thereafter, the application of GM as a drug delivery system for cartilage diseases is introduced. The review then focusses on the emerging application of GM as a carrier for cells and biologics, and biologics delivery within a cartilage construct. The influence of GM on chondrocytes in terms of promoting chondrocyte proliferation and chondrogenic differentiation is highlighted. Furthermore, GM seeded with cells has been shown to have a high tendency to form aggregates; hence the concept of using GM seeded with cells as the building block for the formation of a complex tissue construct. Despite the advancement in GM research, some issues must still be addressed, particularly the improvement of GM’s ability to home to defect sites. As such, the strategy of intraarticular injection of GM seeded with antibody-coated cells is proposed. By addressing this in future studies, a better-targeted delivery system, that would result in more effective intervention, can be achieved.

Autogenous control augmentation system – A refinement in diced cartilage glue graft for augmentation of dorsum of nose

ABSTRACT Background: In the context of different grafts being used for dorsal augmentation, diced cartilage with glue has gained worldwide acceptance. Aims: To develop a system of tools to objectively evaluate the desired dimensions of the required graft for dorsal augmentation and to prepare a corresponding customized-glued-diced cartilage construct. Materials and Methods: A modification of the diced cartilage glue technique called Autogenous control augmentation system (ACAS) was used in ten patients. Results: Of the ten patients, in which this technique was used, eight underwent primary rhinoplasties and two underwent secondary rhinoplasties between July 2017 and December 2017 with a follow-up ranging from 3 to 8 months. In all the cases, the dorsum is straight, and height is maintained. Conclusion: The technique has all the advantages of the diced cartilage glue. The shape resembles alloplastic implant with height and width varying from radix to tip. There is tapering of the cephalic and caudal ends for more natural results. The brow tip aesthetic lines are better defined. The limitation of this study is short follow up.

Successful Low-Cost Scaffold-Free Cartilage Tissue Engineering Using Human Cartilage Progenitor Cell Spheroids Formed by Micromolded Nonadhesive Hydrogel

The scaffold-free tissue engineering using spheroids is pointed out as an approach for optimizing the delivery system of cartilage construct. In this study, we aimed to evaluate the micromolded nonadhesive hydrogel (MicroTissues®) for spheroid compaction (2-day culture) and spontaneous chondrogenesis (21-day culture) using cartilage progenitors cells (CPCs) from human nasal septum without chondrogenic stimulus. CPC spheroids showed diameter stability (486 μm ± 65), high percentage of viable cells (88.1 ± 2.1), and low percentage of apoptotic cells (2.3%). After spheroid compaction, the synthesis of TGF-β1, TGF-β2, and TGF-β3 was significantly higher compared to monolayer (p<0.005). Biomechanical assay revealed that the maximum forces applied to spheroids after chondrogenesis were 2.6 times higher than for those cultured for 2 days. After spontaneous chondrogenesis, CPC spheroids were entirely positive for N-cadherin, collagen type II and type VI, and aggrecan and chondroitin sulfate. Comparing to monolayer, the expression of SOX5 and SOX6 genes analyzed by qPCR was significantly upregulated (p<0.01). Finally, we observed the capacity of CPC spheroids starting to fuse. To the best of our knowledge, this is the first time in the scientific literature that human CPC spheroids were formed by micromolded nonadhesive hydrogel, achieving a successful scaffold-free cartilage engineering without chondrogenic stimulus (low cost).