Symptomatic articular cartilage defects are one of the most common knee injuries, arising from acute trauma, overuse, ligamentous instability, malalignment, meniscectomy, osteochondritis dissecans. Surgical treatment options include bone marrow–stimulating techniques such as abrasion arthroplasty and microfracture, osteochondral mosaicplasty, corrective osteotomy, cartilage resurfacing techniques and tissue engineering techniques using combinations of autologous cells (chondrocytes and mesenchymal stem cells), bioscaffolds, and growth factors. Matrix induced autologous chondrocyte implantation (MACI) is considered the most surgically simple form of autologous chondrocyte implantation. Our group has involved in the development of MACI since 2000 and has led to the FDA approval of MACI as the first tissue engineering product for cartilage repair in 2016. In this article, we have documented the characterisation of autologous chondrocytes, the surgical procedure of MACI and the long term clinical assessment (15 years) of patients with treatment of MACI. We have also reported the retrospective survey in patients with MACI in Australia. Our results suggest that MACI has gained good to excellent long term clinical outcome and probably can delay total knee replacement. However, restoration of hyaline-like cartilage by MACI may be interrupted by the osteoarthritic condition of the joint in patients with progressed osteoarthritis. In addition, because articular cartilage and subchondral bone are considered a single functional unit that is essential for joint function, many cartilage repair technologies including MACI and microfractures have failed short to address the functional barrier structure of osteochondral unit. Further studies are required to develop tissue engineering osteochondral construct that is able to fulfil the function of articular cartilage-subchondral bone units.

Orthopaedic infection with bacteria leads to high societal cost and is detrimental to the life quality. Particularly, deep bone infection leading to osteomyelitis results in an inflammatory response whereby localized bone destruction occurs. Current treatments like antibiotic-containing polymethymethacrylate (PMMA) still has the high risk of bacterial resistance. Taking advantages of silver which has antibacterial and anti-inflammatory effect and bioactive collagen, we fabricated a silver nanoparticle (AgNP)-coated collagen membrane by sonication and sputtering. SEM showed good deposition of AgNPs on collagen membrane by both coating methods. The optimal coating concentration was finalized by assessing optimal antibacterial effect against cytotoxicity and finally collagen membrane coated with 1mg/mL AgNPs solution was selected. We also found that the coated collagen membrane demonstrating short-term cytotoxicity within 24 hours with damage to the cell membrane, which was evidenced by MTS and LDH release test, but had no significant influence (p > 0.05) thereafter. The amount of released AgNPs from coated collagen membrane had negligible cytotoxicity (p > 0.05). Confocal laser scanning microscope displayed similar cell morphology in both coated and uncoated collagen membrane. ELISA and qPCR presented the decreased secretion and expression (p < 0.001) of IL-6 and TNF-alpha. Upregulated expression (p < 0.001) of osteogenesis markers (RUNX2, ALP and OPN) could be found and this might be attributed to the modified collagen fibre surface coated by AgNPs. Collectively, the osteogenesis induced by AgNPs demonstrates a promising application in orthopaedic surgery for its use both as an antimicrobial agent, and to enhance bone regeneration.

Osteocytes are terminally differentiated long-lived cells and account for greater than 95% of the bone cell population. It has been established that osteocytes are connected through their highly developed dendritic network, which is necessary for the maintenance of optimal bone homeostasis. However, little is known on how osteocytes use the network to coordinate their cellular function and communication that requires energy and protein turnover. Here using super-resolution confocal imaging on both live and fixed osteocytes, we demonstrated conclusively that mitochondria are widely distributed and dynamically shared between osteocytes. Using confocal live cell imaging analysis we showed that inhibiting the contact between mitochondria and endoplasmic reticulum (ER) by the knockdown of MFN2 in osteocytes impedes the transfer of mitochondria suggesting the involvement of ER contact with mitochondria in the transfer process. Moreover, we showed that transport of mitochondria between osteocytes within the network enables rescue of osteocytes with dysfunction of mitochondria. Using the 3D tetraculture system with confocal imaging, we identify the transfer of mitochondria from healthy osteocytes enables recovery of mitochondria activities in osteocytes that devoid of mitochondrial DNA by ethidium bromide. The results indicated that when osteocytes are depleted of functional mitochondria, normal parental osteocytes can transfer mitochondria to these stressed osteocytes to provide them with energy. Collectively we show for the first time that the utilisation of mitochondrial transfer enables osteocytes to function with a network and coordinate their cellular activities in response to different energy demands.