Abstract:This study describes a screening platform for a guided in situ vascular tissue engineering approach. Polymer rods were developed that upon 3 weeks of subcutaneous implantation evoke a controlled inflammatory response culminating in encapsulation by a tube-shaped autologous fibrocellular tissue capsule, which can form a basis for a tissue-engineered blood vessel. Rods of co-polymer were produced using different ratios of poly(ethylene oxide terephthalate) and poly(butylene terephthalate) to create a range of ph… Show more
“…To provide the maximum in situ tissue regeneration support, an ideal material device is also required to ensure the efficient and controlled biological clearance of the degraded materials to minimize FBR because the efficacy and safety of implanted biomaterials are often compromised by host immune recognition and subsequent FBRs . Given that tracking of biomaterial degradation in vivo is vital for the rational design of scaffolds, non‐invasive in vivo imaging of biomaterials has been achieved using in situ gel‐forming compounds that carry suitable imaging agents .…”
Section: Recreating Cell–ecm Interactions In a Cell Homementioning
Distilling complexity to advance regenerative medicine from laboratory animals to humans, in situ regeneration will continue to evolve using biomaterial strategies to drive endogenous cells within the human body for therapeutic purposes; this approach avoids the need for delivering ex vivo‐expanded cellular materials. Ensuring the recruitment of a significant number of reparative cells from an endogenous source to the site of interest is the first step toward achieving success. Subsequently, making the “cell home” cell‐friendly by recapitulating the natural extracellular matrix (ECM) in terms of its chemistry, structure, dynamics, and function, and targeting specific aspects of the native stem cell niche (e.g., cell–ECM and cell–cell interactions) to program and steer the fates of those recruited stem cells play equally crucial roles in yielding a therapeutically regenerative solution. This review addresses the key aspects of material‐guided cell homing and the engineering of novel biomaterials with desirable ECM composition, surface topography, biochemistry, and mechanical properties that can present both biochemical and physical cues required for in situ tissue regeneration. This growing body of knowledge will likely become a design basis for the development of regenerative biomaterials for, but not limited to, future in situ tissue engineering and regeneration.
“…To provide the maximum in situ tissue regeneration support, an ideal material device is also required to ensure the efficient and controlled biological clearance of the degraded materials to minimize FBR because the efficacy and safety of implanted biomaterials are often compromised by host immune recognition and subsequent FBRs . Given that tracking of biomaterial degradation in vivo is vital for the rational design of scaffolds, non‐invasive in vivo imaging of biomaterials has been achieved using in situ gel‐forming compounds that carry suitable imaging agents .…”
Section: Recreating Cell–ecm Interactions In a Cell Homementioning
Distilling complexity to advance regenerative medicine from laboratory animals to humans, in situ regeneration will continue to evolve using biomaterial strategies to drive endogenous cells within the human body for therapeutic purposes; this approach avoids the need for delivering ex vivo‐expanded cellular materials. Ensuring the recruitment of a significant number of reparative cells from an endogenous source to the site of interest is the first step toward achieving success. Subsequently, making the “cell home” cell‐friendly by recapitulating the natural extracellular matrix (ECM) in terms of its chemistry, structure, dynamics, and function, and targeting specific aspects of the native stem cell niche (e.g., cell–ECM and cell–cell interactions) to program and steer the fates of those recruited stem cells play equally crucial roles in yielding a therapeutically regenerative solution. This review addresses the key aspects of material‐guided cell homing and the engineering of novel biomaterials with desirable ECM composition, surface topography, biochemistry, and mechanical properties that can present both biochemical and physical cues required for in situ tissue regeneration. This growing body of knowledge will likely become a design basis for the development of regenerative biomaterials for, but not limited to, future in situ tissue engineering and regeneration.
“…Feasibility and safety up to 12 months in pediatric patients. 21 PGS + PCL sheath Porous electrospun PGS core with PCL reinforcement Mouse (IA) Long-term (1 year) functionality in arterial circulation in mice, luminal enlargement 198 PCL Electrospun microfibrous grafts Rat (AA), Pig (CA) Feasibility of regenerative PCL grafts in arterial circulation vs. ePTFE graft 130 , 199 Hyaluronan-based graft Coated onto rotating steel core Rat (AA), Rat (IVC), Pig (CA) Feasibility of regenerative hyaluronan grafts in arterial and venous circulation 200 – 202 In vivo engineered autologous tissue capsule Fibrocellular matrix created by controlling the FBR to subcutaneously implanted rods Pig (CA) Control of FBR to create fibrocellular vascular grafts with sufficient mechanical strength 203 , 204 Decellu-larized SIS Heparin + VEGF functionalized Sheep (CA) Successful in situ regeneration in arterial circulation in large animal 205 EC/SMC preseeded with fibrin Sheep (CA) Successful in situ regeneration in arterial circulation in large animal; cell pre-seeding beneficial but not required 206 Decellulariz-ed de novo engineered allograft In vitro tissue-engineered vascular graft from human cells, decellularized Baboon (AV access) Grafts maintain functionality in a high flow environment, suitable for hemodialysis. 207 Decellulariz-ed de novo engineered allograft In vitro tissue-engineered vascular graft, decellularized Growing lamb (PA) Grafts show somatic growth and maintain functionality up to ~1 year follow-up 20 Comorbidities PCL ± RGD Nanofibrous grafts Rat (AA), healthy vs. type II diabetic Increased complications and impaired regenerative capacity in diabetic vs. healthy rats …”
There is a persistent and growing clinical need for readily-available substitutes for heart valves and small-diameter blood vessels. In situ tissue engineering is emerging as a disruptive new technology, providing ready-to-use biodegradable, cell-free constructs which are designed to induce regeneration upon implantation, directly in the functional site. The induced regenerative process hinges around the host response to the implanted biomaterial and the interplay between immune cells, stem/progenitor cell and tissue cells in the microenvironment provided by the scaffold in the hemodynamic environment. Recapitulating the complex tissue microstructure and function of cardiovascular tissues is a highly challenging target. Therein the scaffold plays an instructive role, providing the microenvironment that attracts and harbors host cells, modulating the inflammatory response, and acting as a temporal roadmap for new tissue to be formed. Moreover, the biomechanical loads imposed by the hemodynamic environment play a pivotal role. Here, we provide a multidisciplinary view on in situ cardiovascular tissue engineering using synthetic scaffolds; starting from the state-of-the art, the principles of the biomaterial-driven host response and wound healing and the cellular players involved, toward the impact of the biomechanical, physical, and biochemical microenvironmental cues that are given by the scaffold design. To conclude, we pinpoint and further address the main current challenges for in situ cardiovascular regeneration, namely the achievement of tissue homeostasis, the development of predictive models for long-term performances of the implanted grafts, and the necessity for stratification for successful clinical translation.
“…It is known that the surface characteristics of an implanted biomaterial are key in driving the FBR and fibrous capsule formation [18, 51]. Ultimately, we aim to develop a TEBV to be used as vascular access site for hemodialysis.…”
Section: Overview Of Approaches For In Situ Vascular Tissue Engineeringmentioning
confidence: 99%
“…This involves an implantable biomaterial, which elicits a FBR to allow the growth of tissue around it (Figure 1.). TEBV’s made in this way would be non-toxic, elicit no immune response, and be free of pre-existing disease as the tissue is completely autologous, none of the initial foreign material remains in the body to propagate an immune response [18]. Fig.…”
It is well known that the number of patients requiring a vascular grafts for use as vessel replacement in cardiovascular diseases, or as vascular access site for hemodialysis is ever increasing. The development of tissue engineered blood vessels (TEBV’s) is a promising method to meet this increasing demand vascular grafts, without having to rely on poorly performing synthetic options such as polytetrafluoroethylene (PTFE) or Dacron. The generation of in vivo TEBV’s involves utilizing the host reaction to an implanted biomaterial for the generation of completely autologous tissues. Essentially this approach to the development of TEBV’s makes use of the foreign body response to biomaterials for the construction of the entire vascular replacement tissue within the patient’s own body. In this review we will discuss the method of developing in vivo TEBV’s, and debate the approaches of several research groups that have implemented this method.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
