Injectable, drug-releasing hydrogel scaffolds with multifunctional properties including hemostasis and anti-bacterial activity are essential for successful wound healing; however, designing ideal materials is still challenging. Herein, we demonstrate the fabrication of a biodegradable, temperature-pH dual responsive supramolecular hydrogel (SHG) scaffold based on sodium alginate/poly(N-vinyl caprolactam) (AG/PVCL) through free radical polymerization and the subsequent chemical and ionic cross-linking. A natural therapeutic molecule, tannic acid (TA)-incorporated SHG (AG/PVCL-TA), was also fabricated and its hemostatic and wound healing efficiency were studied. In the AG/PVCL-TA system, TA acts as a therapeutic molecule and also substitutes as an effective gelation binder. Notably, the polyphenol-arm structure and diverse bonding abilities of TA can hold polymer chains through multiple bonding and co-ordinate cross-linking, which were vital in the formation of the mechanically robust AG/PVCL-TA. The SHG formation was successfully balanced by varying the composition of SA, VCL, TA and cross-linkers. The AG/PVCL-TA scaffold was capable of releasing a therapeutic dose of TA in a sustained manner under physiological temperature-pH conditions. AG/PVCL-TA displayed excellent free radical scavenging, anti-inflammatory, anti-bacterial, and cell proliferation activity towards the 3T3 fibroblast cell line. The wound healing performance of AG/PVCL-TA was further confirmed in skin excision wound models, which demonstrated the potential application of AG/PVCL-TA for skin regeneration and rapid wound healing.

Background: Radiation therapy is a widely employed modality that is used to destroy cancer cells, but it also tends to induce changes in the tumor microenvironment and promote angiogenesis. Radiation, when used as a sole means of therapeutic approach to treat cancer, tends to trigger the angiogenic pathways, leading to the upregulation of several angiogenic growth factors such as VEGF, bFGF, PDGF and angiogenin. This uncontrolled angiogenesis leads to certain angiogenic disorders like vascular outgrowth and an increase in tumor progression that can pose a serious threat to patients.Objective: This review emphasizes on various components of the tumor microenvironment, angiogenic growth factors and biological effects of radiation on tumors in provoking the relapse. It also describes the angiogenic mechanisms that trigger the tumor relapse after radiation therapy and how angiogenesis inhibitors can help in overcoming this phenomenon. It gives an overview of various angiogenesis inhibitors in pre-clinical as well as in clinical trials.Conclusion: The review focuses on the beneficial effects of the combinatorial therapeutic approach of anti-angiogenesis therapy and radiation in tumor management.