Creating In Vitro Three-Dimensional Tumor Models: A Guide for the Biofabrication of a Primary Osteosarcoma Model.

Osteosarcoma (OS) is a highly aggressive primary bone tumor. The mainstay for its treatment is multiagent chemotherapy and surgical resection, with a 50-70% 5-year survival rate. Despite the huge effort made by clinicians and researchers in the past 30 years, limited progress has been made to improve patient outcomes. As novel therapeutic approaches for OS become available, such as monoclonal antibodies, small molecules, and immunotherapies, the need for OS preclinical model development becomes equally pressing. Three-dimensional (3D) OS models represent an alternative system to study this tumor: In contrast to two-dimensional monolayers, 3D matrices can recapitulate key elements of the tumor microenvironment (TME), such as the cellular interaction with the bone mineralized matrix. The advancement of tissue engineering and biofabrication techniques enables the incorporation of specific TME aspects into 3D models, to investigate the contribution of individual components to tumor progression and enhance understanding of basic OS biology. The use of biomaterials that mimic the extracellular matrix could also facilitate the testing of drugs targeting the TME itself, allowing a larger range of therapeutics to be tested, while averting the ethical implications and high cost associated with in vivo preclinical models. This review aims at serving as a practical guide by delineating the OS TME ("what it is like") and, in turn, propose various biofabrication strategies to create a 3D model ("how to recreate it"), to improve the in vitro representation of the OS tumor and ultimately generate more accurate drug response profiles.

Evaluation of the efficacy of cysteamine cream compared to hydroquinone in the treatment of melasma: A randomised, double-blinded trial.

BACKGROUND/OBJECTIVE: Melasma is a commonly acquired disorder of hyperpigmentation that often poses a therapeutic challenge for dermatologists. Recently, cysteamine cream has shown promising results compared to placebo. This study aims to determine the efficacy of cysteamine cream compared to hydroquinone cream in the treatment of melasma. METHODS: A randomised, double-blinded, single-centre trial was conducted in Victoria, Australia. 20 recruited participants were given either cysteamine cream or hydroquinone cream for 16 weeks. The primary outcome measure was a change in the modified Melasma Area and Severity Index (mMASI). Quality of life at baseline and week 16 as well as standard digital photography at each follow-up visit was assessed as secondary outcome measures. RESULTS: At week 16, 14 participants completed the study with 5 participants in the cysteamine group and 9 patients in the hydroquinone group. In the intention to treat analysis, there was a 1.52 ± 0.69 (21.3%) reduction in mMASI for the cysteamine group and a 2.96 ± 1.15 (32%) reduction in the hydroquinone group. The difference between groups was not statistically significant (P = 0.3). Hydroquinone cream was generally better tolerated that cysteamine cream. CONCLUSION: Our study suggests that topical cysteamine may have comparable efficacy to topical hydroquinone. Cysteamine thus provides a possible alternative to patients and clinicians who wish to avoid or rotate off topical hydroquinone. While side effects were more common for participants using cysteamine compared with hydroquinone, these were mild and reversible. Larger studies comparing cysteamine and hydroquinone are required to support these findings.