The development of biomaterials, stem cells and bioactive factors has led to cartilage tissue engineering becoming a promising tactic to repair cartilage defects. Various polymer three-dimensional scaffolds that provide an extracellular matrix (ECM) mimicking environment play an important role in promoting cartilage regeneration. In addition, numerous growth factors have been found in the regenerative process. However, it has been elucidated that the uncontrolled delivery of these factors cannot fully exert regenerative potential and can also elicit undesired side effects. Considering the complexity of the ECM, neither scaffolds nor growth factors can independently obtain successful outcomes in cartilage tissue engineering. Therefore, collectively, an appropriate combination of growth factors and scaffolds have great potential to promote cartilage repair effectively; this approach has become an area of considerable interest in recent investigations. Of late, an increasing trend was observed in cartilage tissue engineering towards this combination to develop a controlled delivery system that provides adequate physical support for neo-cartilage formation and also enables spatiotemporally delivery of growth factors to precisely and fully exert their chondrogenic potential. This review will discuss the role of polymer scaffolds and various growth factors involved in cartilage tissue engineering. Several growth factor delivery strategies based on the polymer scaffolds will also be discussed, with examples from recent studies highlighting the importance of spatiotemporal strategies for the controlled delivery of single or multiple growth factors in cartilage tissue engineering applications.

Background Knee osteoarthritis (OA) is one of the most common joint diseases, and pharmacotherapy is necessary to control its symptoms. Aim To evaluate efficacy and tolerability of duloxetine in patients with knee OA. Methods PubMed, Web of Science, Embase, Cochrane Library and http://ClinicalTrials.gov were searched to identify randomised controlled trials comparing duloxetine with placebo for knee OA. Data including pain, stiffness, physical function, and adverse events were extracted for meta‐analysis. The protocol was prospectively registered in PROSPERO (CRD42018097110). Results Data from six randomised controlled trials including 2059 participants were pooled. Duloxetine achieved significant reductions in primary outcomes including Brief Pain Inventory 24‐h average pain score (weighted mean difference (WMD) = −0.74, 95% confidence interval (CI) = −0.92 to −0.57), weekly mean of the 24‐h average pain score (WMD = −0.76, 95% CI = −0.96 to −0.56), WOMAC stiffness score (WMD = −0.47, 95% CI = −0.60 to −0.34) and WOMAC physical function score (WMD = −4.44, 95% CI = −5.24 to −3.64). Furthermore, duloxetine demonstrated a higher number of treatment‐emergent adverse events (risk ratio (RR) = 1.31, 95% CI = 1.20–1.44) and discontinuations (RR = 2.26, 95% CI = 1.63–3.12); however, no difference in serious adverse events (RR = 0.92, 95% CI = 0.40–2.11) was observed. Conclusion Duloxetine is effective in the management of chronic pain and loss of physical function in knee OA with acceptable adverse events despite having no advantage in treating joint stiffness. Future trials should focus on determining the optimal treatment regimen.