Biological scaffold or implant is a popular choice for the preparation of tissue-engineered organs and has the potential to address donor shortage in the clinics. However, biological scaffolds prepared by physical or chemical agents cause damage to the extracellular matrix by potentially inducing immune responses after implantation. The current study explores an alternative route for the preparation of acellular scaffolds and explores the fate of the prepared scaffolds in a milieu of immune cells following implantation without using immunosuppressant. Using the syngeneic (Lewis male-Lewis female) and allogeneic (Brown Norway male-Lewis female) models and different tissue routes (subcutaneous vs omentum) for transplantation, normal blood vascular scaffolds were implanted which was converted to acellular vascular scaffolds by in vivo natural decellularization at the end of 2 months of observation. We also prepared chemically decellularized acellular scaffolds from normal untreated blood vascular scaffolds using a cocktail of chemicals which was also similarly placed in subcutaneous and omentum sites. Here, we applied in-depth quantitative proteomics along with histology and image analysis to comprehensively describe and compare the proteome of the natural and chemically decellularized scaffold. Our data confirm that site-specific advantages exist in modulating the ECM and regulating the immune responses (macrophage and T cells) following implantation, which possibly led to the production of an acellular scaffold (natural decellularization) under in vivo conditions. The current approach opens up the possibility to create tailor-made acellular scaffolds to build functional blood vessels. In addition, the identification of different tissue sites facilitates differential immune response against the scaffolds. This study provides a rich resource aimed toward an enhanced mechanistic understanding to study immune responses under similar settings in the field of transplantation and regenerative medicine.

The development of a suitable biological scaffold or implant is a pre-requisite for the functional development of organs including blood vessels. Biological scaffold prepared by physical or chemical agents cause damage to the extracellular matrix architecture and induce immune response after scaffold implantation/engraftment. During the current study, taking advantage of different host tissue environments (subcutaneous vs omentum), acellular scaffolds/implants were prepared based on syngeneic vs allogeneic model of scaffold implantation (in vivo decellularization) and compared with chemically decellularized scaffolds. Employing molecular, proteomics, and histologic techniques, we confirmed that site-specific advantages exist in modulating the ECM as well as regulating the immune responses (macrophage and T-cells) to produce an acellular scaffold without the need for immunosuppressants. The current approach opens up the possibility to create tailor-made scaffolds for further use in the clinics with a potential for long term acceptability without eliciting adverse reactions in the host. The scaffolds prepared thus would open up a further possibility to build functional organs following cell engraftment.Impact statementDuring the current study an alternative strategy of preparing a scaffold by natural means was investigated which would also give an option to avoid the detrimental effect of chemicals used while preparing a biological scaffold. Understanding the cellular milieu of an implanted scaffold would help to modify the immunological trigger upon scaffold implantation, an aspect also studied during the current research. The infiltrating cells and their putative relationship with the biological scaffold could help the researcher to target immune cells to avoid scaffold/implant rejection. In a nutshell, the study carried out without any immunosuppressive agents could help further exploration of (a) alternative strategies for preparing biological scaffolds and (b) implantable sites as potential bioreactors with the aim to avoid any adverse immune reactions for further acceptance of the scaffold/implant post implantation.

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Background: Stenosis of cerebral aqueduct (CA) is featured in many studies related to elevated intracranial cerebral pressures (ICP). It also presents a challenging situation to clinicians. Compressive forces play a lead role in pathological situations like tumor presence and hence can cause obstruction to the flow of cerebrospinal fluid (CSF). Due to this barrier, excessive retention of CSF in ventricles can occur. This in turn could contribute to increased pressure gradients inside the cranium. In literature, most of the numerical models are restricted to modeling the CSF flow by considering ventricle walls as rigid material unlike its behavior a deformable character. This paper, therefore, addresses the same from a holistic perspective by taking into consideration the dynamics of the flexible character of the ventricular wall. This adds to the novelty of this work by reconstructing an anatomically realistic ventricular wall behavior. To do this, the authors aim to develop a computational model of stenosis of CA due to brain tumor by invoking a fluid-structure interaction (FSI) method. The proposed 3D FSI model is simulated under two cases. First, simulation of pre-stenosis case with no interaction of tumor forces and secondly, a stenosis condition together-with dynamic interaction of tumor forces. Results: Comparing the forces with and without tumor reveals a marked obstruction of CSF outflow post third ventricle and the cerebral aqueduct. Not only this but a drastic rise of CSF velocity from 21.2 mm/s in pre-stenosis case to 54.1 mm/s stenosis case is also observed along with a net deformation increase of 0.144 mm on walls of ventricle. Conclusions: This is a significant contribution to brain simulation studies for pressure calculations, wherein the presence of tumors is a major concern.