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The dura mater protects underlying tissues and cerebrospinal fluid, but dural abnormalities can cause leaking and meningitis and wound infections. This review emphasizes the relevance of dural repair and the progress of dural reconstruction materials, focusing on biological scaffolds. A comprehensive assessment of dural substitution literature focused on composite, acellular, natural, synthetic, and homologous materials. Decellularized dura scaffolds as viable natural biomaterials for tissue engineering are explored in this overview of these materials' properties, effectiveness, and therapeutic uses. The evaluation also compares materials and assesses host tissue response in preclinical and clinical studies. The review highlights various dural substitution findings. There is no gold standard for dural repair, despite the variety of materials used. Replicating natural dura mater's mechanical and structural qualities is difficult. Recent research suggests that decellularized dura scaffolds can regenerate tissue while reducing inflammation and transplant rejection. Furthermore, the movement toward personalized medicine in this sector suggests that bespoke alternatives might be chosen depending on patient characteristics, improving treatment effects. Synthesizing dural replacement research and clinical uses in this review adds to knowledge. It tackles standard materials' shortcomings and shows how biological scaffolds might improve dural repair. The analysis opens the door to personalized dural repair research that might enhance patient outcomes and advance neurosurgery. The insights presented herein highlight the intriguing prospects for appropriate dural restorative materials, seeking to improve dural defect treatment. [ABSTRACT FROM AUTHOR]

Decellularized matrices derived from diseased tissues/organs have evolved in the most recent years, providing novel research perspectives for understanding disease occurrence and progression and providing accurate pseudo models for developing new disease treatments. Although decellularized matrix maintaining the native composition, ultrastructure, and biomechanical characteristics of extracellular matrix (ECM), alongside intact and perfusable vascular compartments, facilitates the construction of bioengineered organ explants in vitro and promotes angiogenesis and tissue/organ regeneration in vivo, the availability of healthy tissues and organs for the preparation of decellularized ECM materials is limited. In this paper, we review the research advancements in decellularized diseased matrices. Considering that current research focuses on the matrices derived from cancers and fibrotic organs (mainly fibrotic kidney, lungs, and liver), the pathological characterizations and the applications of these diseased matrices are mainly discussed. Additionally, a contrastive analysis between the decellularized diseased matrices and decellularized healthy matrices, along with the development in vitro 3D models, is discussed in this paper. And last, we have provided the challenges and future directions in this review. Deep and comprehensive research on decellularized diseased tissues and organs will promote in‐depth exploration of source materials in tissue engineering field, thus providing new ideas for clinical transformation. [ABSTRACT FROM AUTHOR]

Recently, a decellularized microvascular graft (inner diameter: 0.6 mm) modified with the integrin α4β1 ligand, REDV, was developed to provide an alternative to autologous‐vein grafting in reconstructive microsurgery, showing good early‐stage patency under arterial flow in rats. This consecutive study evaluated its potential utility not only as an arterial substitute, but also as a venous substitute, using a rat‐tail replantation model. Graft remodeling depending on hemodynamic status was also investigated. ACI rat tail arteries were decellularized via ultra‐high‐hydrostatic pressure treatment and modified with REDV to induce antithrombogenic interfaces and promote endothelialization after implantation. Grafts were implanted into the tail artery and vein to re‐establish blood circulation in amputated Lewis rat tails (n = 12). The primary endpoint was the survival of replants. Secondary endpoints were graft patency, remodeling, and regeneration for 6 months. In all but three cases with technical errors or postoperative self‐mutilation, tails survived without any evidence of ischemia or congestion. Six‐month Kaplan–Meier patency was 100% for tail‐artery implanted grafts and 62% for tail‐vein implanted grafts. At 6 months, the neo‐tunica media (thickness: 95.0 μm in tail‐artery implanted grafts, 9.3 μm in tail‐vein implanted grafts) was regenerated inside the neo‐intima. In conclusion, the microvascular grafts functioned well both as arterial and venous paths of replanted‐rat tails, with different remodeling under arterial and venous conditions. [ABSTRACT FROM AUTHOR]

Upper limb muscle reconstruction is required following cancer resection, trauma, and congenital deformities. Current surgical reconstruction of the muscle involves local, regional and free flaps. However, muscle reconstruction is not always possible due to the size of the defect and functional donor site morbidity. These challenges could be addressed with the production of scaffolds composed of an extracellular matrix (ECM) derived from decellularized human skeletal muscle. This study aimed to find an optimal technique to decellularize a flexor digitorum superficialis muscle. The first two protocols were based on a detergent only (DOT) and a detergent‐enzymatic protocol (DET). The third protocol avoided the use of detergents and proteolytic enzymes (NDNET). The decellularized scaffolds were characterized using qualitative techniques including histological and immunofluorescent staining and quantitative techniques assessing deoxyribonucleic acid (DNA), glycosaminoglycan (GAG), and collagen content. The DOT protocol consisting of 2% SDS for 4 hours was successful at decellularizing human FDS, as shown by DNA content assay and nuclei immunofluorescence staining. The DOT protocol maintained the microstructure of the scaffolds as shown by Masson's trichrome staining and collagen and GAG content. DET and NDNET protocols maintained the ECM, but were unsuccessful in removing all DNA content after two cycles of decellularization. Decellularization of skeletal muscle is a viable option for muscle reconstruction using a detergent only technique for upper limb defects. Further testing in vivo will assess the effectiveness of decellularized scaffolds for upper limb muscle skeletal tissue engineering. [ABSTRACT FROM AUTHOR]

Abstract: Hydrogels, highly‐hydrated crosslinked polymer networks, closely mimic the microenvironment of native extracellular matrix (ECM) and thus present as ideal platforms for three‐dimensional cell culture. Hydrogels derived from tissue‐ and organ‐specific decellularized ECM (dECM) may retain bioactive signaling cues from the native tissue or organ that could in turn modulate cell–material interactions and response. In this study, we demonstrate that porcine kidney dECM can be processed to form hydrogels suitable for cell culture and encapsulation studies. Scanning electron micrographs of hydrogels demonstrated a fibrous ultrastructure with interconnected pores, and rheological analysis revealed rapid gelation times with shear moduli dependent upon the protein concentration of the hydrogels. Conditionally‐immortalized human glomerular endothelial cells (GEnCs) cultured on top of or encapsulated within hydrogels exhibited high cell viability and proliferation over a one‐week culture period. However, gene expression analysis of GEnCs encapsulated within kidney dECM hydrogels revealed significantly lower expression of several relevant genes of interest compared to those encapsulated within hydrogels composed of only purified collagen I. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A:2448–2462, 2018. [ABSTRACT FROM AUTHOR]

Tissue extracellular matrix (ECM) is a complex material made up of fibrous proteins and ground substance (glycosaminoglycans, GAGs) that are secreted by cells. ECM contains important biological cues that modulate cell behaviors, and it also serves as a structural scaffold to which cells can adhere. For clinical applications, where immune rejection is a constraint, ECM can be processed using decellularization methods intended to remove cells and donor antigens from tissue or organs, while preserving native biological cues essential for cell growth and differentiation. In this study, a decellularized ECM-based composite hydrogel was formulated by using modified GAGs that covalently bind tissue particles. These GAG-ECM composite hydrogels combine the advantages of solid decellularized ECM scaffolds and pepsin-digested ECM hydrogels by facilitating ECM hydrogel formation without a disruptive enzymatic digestion process. Additionally, engineered hydrogels can contain more than one type of ECM (from bone, fat, liver, lung, spleen, cartilage, or brain), at various concentrations. These hydrogels demonstrated tunable gelation kinetics and mechanical properties, offering the possibility of numerous in vivo and in vitro applications with different property requirements. Retained bioactivity of ECM particles crosslinked into this hydrogel platform was confirmed by the variable response of stem cells to different types of ECM particles with respect to osteogenic differentiation in vitro, and bone regeneration in vivo. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 147-159, 2018. [ABSTRACT FROM AUTHOR]

There is a clinical need to provide replacement tracheal tissue for the pediatric population affected by congenital defects, as current surgical solutions are not universally applicable. A potential solution is to use tissue engineered scaffold as the framework for regenerating autologous tissue. Rabbit trachea were used and different detergents (Triton x-100 and sodium deoxycholate) and enzymes (DNAse/RNAse) investigated to create a decellularization protocol. Each reagent was initially tested individually and the outcome used to design a combined protocol. At each stage the resultant scaffold was assessed histologically, molecularly for acellularity and matrix preservation. Immunogenicity of the final scaffold was assessed by implantation into a rat model for 4 weeks. Both enzymes and detergents were required to produce a completely acellular (DNA content 42.78 ng/mg) scaffold with preserved collagen and elastin however, GAG content were reduced (8.78 ± 1.35 vs. 5.5 ± 4.8). Following in vivo implantation the scaffold elicited minimal immune response and showed significant cellular infiltration and vasculogenesis. The luminal aspect of the implanted scaffold showed infiltration of host derived cells, which were positive for pan cytokeratin. It is possible to create biologically derived biocompatible scaffolds to address specific pediatric clinical problems. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2126-2135, 2017. [ABSTRACT FROM AUTHOR]

Mesenchymal bone marrow stromal cells may be a source of cells to preseed decellularized biologic mesh materials for improved cellularization and promote a more physiologic tissue after remodeling. Spontaneous differentiation of mesenchymal stromal cells on the decellularized material would be undesirable. Conversely, induced differentiation of mesenchymal stem cells (MSC) on the material would suggest that these materials may have promise as scaffold materials for bone, cartilage, or adipocyte formation. Two sources of mesenchymal cells were evaluated for induced differentiation in control wells. These MSCs were also evaluated for spontaneous or induced differentiation on decellularized porcine dermis and mesothelium materials. Primarily harvested bone marrow MSCs and commercially obtained MSCs were induced into osteoblasts and adipocytes on decellularized dermis and mesothelium materials. The MSCs were able to be induced into chondrocytes in pellet form but not when grown as a monolayer on the materials. The MSCs did not undergo spontaneous differentiation when grown on the materials for up to four weeks. MSC grown on decellularized porcine dermis or mesothelium do not spontaneously differentiate and may serve as a source of autologous cells for preseeding these extracellular matrix materials prior to implantation. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2875-2883, 2014. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis: One potential treatment for vocal fold injury or neoplasia is to replace the entire vocal fold with a tissue-engineered scaffold. This scaffold should ideally have similar mechanical properties and extracellular matrix composition as the native vocal fold. As one approach toward this goal, we decellularized human vocal folds and characterized their mechanical properties and extracellular matrix microstructure. Study Design: Basic science investigation. Methods: Human vocal folds were dissected from the laryngeal framework and treated with sodium dodecyl sulfate (SDS) to remove all cells. Mechanical properties were measured by indentation before and after SDS treatment. The extracellular matrix components of collagen, laminin, elastin, and hyaluronic acid were also characterized before and after decellularization using histology and immunofluorescence. Results: After 4 days of SDS treatment, we obtained a scaffold that retained the original geometry of the vocal fold but was devoid of cells. The elastic modulus of the vocal folds did not change significantly before and after decellularization. Upon qualitative inspection, the decellularized vocal folds retained the original collagen, elastin, and laminin content and orientation but lost the original hyaluronic acid. Conclusions: Vocal folds can be decellularized using SDS without adversely affecting its mechanical stiffness and fibrous extracellular matrix. This preliminary study demonstrates the potential of a decellularized scaffold to serve as a tissueengineered construct for vocal fold replacement. [ABSTRACT FROM AUTHOR]

Heparin treatment of decellularized xenografts has been reported to reduce graft thrombogenicity. However, little is known about the in vivo comparison of heparin-treated with non-heparin-treated xenografts, especially for small-caliber vascular implants. We implanted either a heparin-treated or a non-heparin-treated canine carotid artery as bilateral carotid xenograft in rabbits ( n = 24). Small-caliber xenografts (3∼4 mm) were decellularized by enzymatic and detergent extraction and were further covalently linked with heparin. During implantation, thrombosis rate was 4% in the heparin-treated xenografts and 25% in the non-heparin-treated xenografts after 3 weeks ( P < 0.05). After 6 months, it was 8 versus 58%, respectively ( P < 0.01). Both heparin-treated and non-heparin-treated xenografts harvested at the end of 3 and 6 months showed a satisfactory cellular reconstruction of either smooth muscle cells or endothelial cells. These results indicate that heparin treatment of the small-caliber decellularized xenograft reduces the in vivo thrombogenicity. Both heparin-treated and non-heparin-treated xenografts seem to undergo a similar cellular remodeling process up to 6 months. [ABSTRACT FROM AUTHOR]