Bone tissue engineering using polymer based scaffolds have been studied a lot in last decades. Considering the qualities of all the polymers desired to be used as scaffolds, Polycaprolactone (PCL) polyester apart from being biocompatible and biodegradable qualifies to an appreciable level due its easy availability, cost efficacy and suitability for modification. Its adjustable physio-chemical state, biological properties and mechanical strength renders it to withstand physical, chemical and mechanical, insults without significant loss of its properties. This review aims to critically analyse the efficacy of PCL as a biomaterial for bone scaffolds. 1.1. Polymers as biomaterial for scaffolds The characteristics of a biomaterial that must be scrutinized thoroughly before considering it for bone tissue engineering applications includes chemical composition, biological and structural characteristics, degradation behavior and fabrication process. Polymeric scaffolds are of considerable interest due to their distinctive features, such

(2), or as a negative feedback mechanism to limit Ca 2ϩ entry by hyperpolarizing the plasma membrane and closing voltagedependent Ca 2ϩ channels (3) previously opened by pressure (4) or vasoconstrictors like 5-hydroxytriptamine (5-HT) and Angiotensin II (AngII) (5, 6). In vitro evidence suggests that MaxiK also may play a role in vasoconstriction as it is inhibited by the potent constrictors AngII (7) and thromboxane A2 (8) in bilayers. However, the functional role of MaxiK channels in agonist-induced contraction has not been demonstrated.Pharmacomechanical and biochemical evidence indicate that one mechanism of agonist-induced contraction may involve tyrosine phosphorylation͞dephosphorylation with phosphorylation associated with vasoconstriction (9). However, most studies have been performed by using inhibitors with broad actions (e.g., tyrphostin and genistein) (10, 11). Using more selective inhibitors for Src-family tyrosine kinases, PP1 and PP2 (12) recent studies in rat aorta (13) and mesenteric arteries (14) show that 5-HT and AngII contractions involve a Src tyrosine kinase, likely c-Src. However, the downstream effector(s) of c-Src promoting vasoconstriction are unknown.We hypothesized that MaxiK may be a potential downstream effector of c-Src favoring vasoconstriction. This is based on the facts that both c-Src tyrosine kinase and MaxiK are particularly abundant in smooth muscles including the vasculature (15-18), and that Lavendustin A (LavA), a c-Src and Lck inhibitor (10,19), increases the activity of rat tail artery MaxiK (20). Here, we provide evidence showing that agonist-induced vasoconstriction by 5-HT, AngII, and phenylephrine involves inhibition of MaxiK channels by c-Src via direct phosphorylation of the channel protein. This new signaling pathway has a significant role in human and rat vasoconstriction, providing a link between electromechanical and pharmacomechanical coupling (21). Furthermore, the results indicate that MaxiK channels can function as a rheostat controlling both vasoconstriction and vasorelaxation. Experimental ProceduresTissue. Human coronary arteries were obtained from explanted hearts (University of California, Los Angeles, Medical Center). Male 3-mo-old F344 rats were used. Protocols received institutional approval.Isometric Contraction. Arterial rings (2.0-to 3.0-mm internal diameter, 3 mm long) without endothelium were stretched to an optimal resting tension (2 g, human coronaries; 1.2 g, rat aorta) and equilibrated for 60 min in Krebs solution. Percentage relaxation after drug application was calculated for tonic contractions from: percentage relaxation ϭ (max -min)͞(maxbasal) ϫ 100; where max ϭ maximal steady-state tension after constricting agonist stimulation, min ϭ minimal tension attained after drug application, basal ϭ basal tension prior constricting agonist stimulation. For phasic contractions, percentage relaxation ϭ (cycles͞h before drug application ͞cycles͞h after drug application ) ϫ 100. Because IbTx treatment abolished phasic contractions, in this case p...

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Developing stiff and resilient injectable hydrogels that can mechanically support load-bearing joints while enabling chondrogenic differentiation of stem cells is a major challenge in the field of cartilage tissue engineering. In the present work, a triplenetwork injectable hydrogel system was engineered using Bombyx mori silk fibroin, carboxymethyl cellulose (CMC), and gelatin. The developed hydrogel demonstrated a simultaneous increase in both stiffness and contraction over time, thereby imparting a fourdimensional (4D) evolving niche to the cells. While resilience was provided by CMC, the dynamic alterations in the hydrogel matrix were attributed to the formation of β-sheets in silk. The engineered contraction facilitated condensation of cells that mimicked an important step during cartilage development. Subsequently, this led to downregulation of YAP signaling and enhanced chondrogenic commitment of stem cells. More importantly, the in vivo study showed that the ectopically regenerated cartilage was mature and closely resembled native articular cartilage. Overall, this strategy of engineering mechanotransduction that promotes chondrogenesis by contraction-mediated condensation is a promising and translatable approach for cartilage repair.

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