Wound healing is a common physiological process which consists of a sequence of molecular and cellular events that occur following the onset of a tissue lesion in order to reconstitute barrier between body and external environment. The inherent properties of hydrogels allow the damaged tissue to heal by supporting a hydrated environment which has long been explored in wound management to aid in autolytic debridement. However, chronic non-healing wounds require added therapeutic features that can be achieved by incorporation of biomolecules and supporting cells to promote faster and better healing outcomes. In recent decades, numerous hydrogels have been developed and modified to match the time scale for distinct stages of wound healing. This review will discuss the effects of various types of hydrogels on wound pathophysiology, as well as the ideal characteristics of hydrogels for wound healing, crosslinking mechanism, fabrication techniques and design considerations of hydrogel engineering. Finally, several challenges related to adopting hydrogels to promote wound healing and future perspectives are discussed.
Controlling the formation of new lymphatic vessels has been postulated as an innovative therapeutic strategy for various disease phenotypes, including neurodegenerative diseases, metabolic syndrome, cardiovascular disease, and lymphedema. Yet, compared to the blood vascular system, little is known about the molecular regulation that controls lymphatic tube formation in a synthetic matrix. In this study, we utilize hyaluronic acid (HA)-hydrogels to design a novel platform for decoupled investigation into how mechanical and biochemical cues regulate lymphatic vessel formation in a synthetic matrix. Using HA and controlling the degree of modification provides a method to preserve and modulate key lymphatic markers Prox1, LYVE-1, and Pdpn. The chemistry of the system allows for spatial and temporal patterning of specific peptides and substrate stiffnesses, and an MMP-sensitive crosslinker allowed cells to degrade and remodel their matrix. Through systematic optimization of multiple parameters, we have designed a system that allows human lymphatic endothelial cells (LECs) to self-assemble into vessels in vitro within 3 days. These engineered vessels can be cultured for up to 3 weeks and can be used for high-throughput mechanistic studies, or can be implanted into immunodeficient mice where they have demonstrated the ability to integrate and mature. Collectively, these studies report a novel, fully-defined 3D synthetic matrix system capable of generating lymphatic vessels in vitro that provide promise as an in vitro screening platform and as a therapeutic vessel transplant, which to our knowledge, is the first ever 3D lymphatic tissue engineering approach to not require the use of support cells.
Surface coating with dopamine conjugated hyaluronic acid (HA–DP) can interact with lymphatic vessel endothelial hyaluronan receptor-1 ( LYVE-1 ) to preserve the phenotypes and functionality of lymphatic endothelial cells (LECs).
Introduction: Generating new lymphatic vessels has been postulated as an innovative therapeutic strategy for various disease phenotypes, including neurodegenerative diseases, metabolic syndrome, cardiovascular disease, and lymphedema. Yet, compared to the blood vascular system, protocols to differentiate human induced pluripotent stem cells (hiPSCs) into lymphatic endothelial cells (LECs) are still lacking. Methods: Transcription factors, ETS2 and ETV2 are key regulators of embryonic vascular development, including lymphatic specification. While ETV2 has been shown to efficiently generate blood endothelial cells, little is known about ETS2 and its role in lymphatic differentiation. Here, we describe a method for rapid and efficient generation of LECs using transcription factors, ETS2 and ETV2. Results: This approach reproducibly differentiates four diverse hiPSCs into LECs with exceedingly high efficiency. Timely activation of ETS2 was critical, to enable its interaction with Prox1, a master lymphatic regulator. Differentiated LECs express key lymphatic markers, VEGFR3, LYVE-1, and Podoplanin, in comparable levels to mature LECs. The differentiated LECs are able to assemble into stable lymphatic vascular networks in vitro, and secrete key lymphangiocrine, reelin. Conclusion: Overall, our protocol has broad applications for basic study of lymphatic biology, as well as toward various approaches in lymphatic regeneration and personalized medicine.
Mechanoregulation of cell–extracellular matrix (ECM) interactions are crucial for dictating pluripotent stem cell differentiation. However, not all pluripotent cells respond homogeneously which results in heterogeneous cell populations. When cells, such as mouse epiblast stem cells (EpiSCs), are cultured in clusters, the heterogeneity effect during differentiation is even more pronounced. While past studies implicated variations in signaling pathways to be the root cause of heterogeneity, the biophysical aspects of differentiation have not been thoroughly considered. Here, we demonstrate that the heterogeneity of EpiSC differentiation arises from differences in the colony size and varying degrees of interactions between cells within the colonies and the ECM. Confocal imaging demonstrates that cells in the colony periphery established good contact with the surface while the cells in the colony center were separated by an average of 1–2 µm from the surface. Traction force measurements of the cells within the EpiSC colonies show that peripheral cells generate large tractions while the colony center cells do not. A finite element modeling of EpiSC colonies shows that tractions generated by the cells at the colony periphery lift off the colony center preventing the colony center from undergoing differentiation. Together, our results demonstrate a biophysical regulation of heterogeneous EpiSC colony differentiation.
In developing countries including Bangladesh injuries and deaths due to Road Traffic Accident (RTA) are appeared to be major and alarming problems and it requires noticeable measures and efforts for prevention of morbidity and mortality rate. The objective of present study was to investigate the pattern of injuries in RTA. This descriptive cross-sectional study was conducted among the victims who died of RTA from 2006 to 2012 and were autopsied at Dhaka Medical College Morgue. Among 1000 cases of death due to RTA, the numbers of deaths only due to head injuries are 472, the numbers of death due to head & other injuries are 272 & the numbers of deaths only due to other injuries are 256. According to this study head injury is the most common cause of death due to RTA & which is about 47.2%. Mediscope 2022;9(1): 5-8