Construction Of Scaffolds Research Articles

Advancements in Palladium-Catalyzed formic acid Dehydrogenation: Greening carbon monoxide synthesis in synthetic organic chemistry

The diverse applications of carbon monoxide-containing compounds make the construction of the carbonylation scaffolds, thus attracts the interest of synthetic chemist for exploitation. This review comprehensively summarize the significant advancement of the Pd-catalyzed an efficient and mild carbonylative reactions, with an emphasis on approaches for the generation of carbon monoxide intermediate from formic acid that offers an opportunities to overcome obstacles in the pharmacuticals. Among the CO surrogates, formic acid are more cheaper and environmentally benign methods gained considerable attention with the emergence of newer methods and are advantageous in terms of their good availability, and ease of handling. We have summarized the recent development in carbonylation reactions using formic acid as a surrgoate from past decade. We believe that we discuss provide an overview regarding the the recent progress, challenges, opportunities and future outcomes in the area of the carbonylation chemistry using formic acid available as an Carbon monoxide source.

Design, Synthesis and Molecular Docking Studies of New Indole Scaffolds

AbstractA convenient and straightforward approach for the construction of angular and linear indole scaffolds from commercially available β‐tetralones through a sequential methylation/ allylation/ propargylation followed by ring closing metathesis (RCM)/ [2+2+2] cyclotrimerization and Fischer indolization (FI) sequence has been described. The dipropargyl derivatives were further investigated for Sonogashira cross‐coupling with iodo‐benzene and click chemistry with benzyle azide to synthesize diverse indole motifs. The [2+2+2] cyclotrimerized products were treated with 3,5‐dimethyl aniline to obtain the product that resembles the structure of Alectinib, an FDA approved drug for the treatment of cancer. The approach provides a series of indole derivatives in moderate to good yields with excellent functional group tolerance and hence these compounds are utilized for molecular docking studies which shows good results. All the compounds synthesized here are well characterized by NMR and HRMS data.

Multilayered hydrogel scaffold construct with native tissue matched elastic modulus: A regenerative microenvironment for urethral scar-free healing

The unsuitable deformation stimulus, harsh urine environment, and lack of a regenerative microenvironment (RME) prevent scaffold-based urethral repair and ultimately lead to irreversible urethral scarring. The researchers clarify the optimal elastic modulus of the urethral scaffolds for urethral repair and design a multilayered PVA hydrogel scaffold for urethral scar-free healing. The inner layer of the scaffold has self-healing properties, which ensures that the wound effectively resists harsh urine erosion, even when subjected to sutures. In addition, the scaffold's outer layer has an extracellular matrix-like structure that synergizes with adipose-derived stem cells to create a favorable RME. In vivo experiments confirm successful urethral scar-free healing using the PVA multilayered hydrogel scaffold. Further mechanistic study shows that the PVA multilayer hydrogel effectively resists the urine-induced inflammatory response and accelerates the transition of urethral wound healing to the proliferative phase by regulating macrophage polarization, thus providing favorable conditions for urethral scar-free healing. This study provides mechanical criteria for the fabrication of urethral tissue-engineered scaffolds, as well as important insights into their design.

An evolved artificial radical cyclase enables the construction of bicyclic terpenoid scaffolds via an H-atom transfer pathway.

While natural terpenoid cyclases generate complex terpenoid structures via cationic mechanisms, alternative radical cyclization pathways are underexplored. The metal-catalysed H-atom transfer reaction (M-HAT) offers an attractive means for hydrofunctionalizing olefins, providing access to terpenoid-like structures. Artificial metalloenzymes offer a promising strategy for introducing M-HAT reactivity into a protein scaffold. Here we report our efforts towards engineering an artificial radical cyclase (ARCase), resulting from anchoring a biotinylated [Co(Schiff-base)] cofactor within an engineered chimeric streptavidin. After two rounds of directed evolution, a double mutant catalyses a radical cyclization to afford bicyclic products with a cis-5-6-fused ring structure and up to 97% enantiomeric excess. The involvement of a histidine ligation to the Co cofactor is confirmed by crystallography. A time course experiment reveals a cascade reaction catalysed by the ARCase, combining a radical cyclization with a conjugate reduction. The ARCase exhibits tolerance towards variations in the dienone substrate, highlighting its potential to access terpenoid scaffolds.

Rapid Construction of Polycyclic Skeletons via Brønsted-Base-Catalyzed Annulations of Ethylidene 1,3-Indenediones and Vinyl 1,2-Diketones.

Brønsted-base-catalyzed diversified annulations between ethylidene 1,3-indenediones and vinyl 1,2-diketones have been achieved, delivering three types of products containing oxabicyclo[3.2.1]octane, spiro[4.5]decane, and branched triquinane skeletons, respectively, which widely exist in natural products and bioactive substances. Two unprecedented reaction modes have been disclosed, and the reactions could be readily scaled up. The protocol shows the potential of 1,2-diketone-mediated reactions in the rapid construction of complicated polycyclic scaffolds.

Trihaloisocyanuric Acids: Useful Reagents for Halogenation Reactions and Heterocyclic Scaffold Construction

Abstract: Trihaloisocyanuric acids [1,3,5-trihalo-1,3,5-triazine-2,4,6-(1H,3H,5H)-triones] are commercially available or easily prepared solids. They are highly reactive, stable, easily handled, and have an excellent atom economy, transferring up to three halogen atoms to organic substrates. In these regards, the present review summarizes their synthetic applications as safe and convenient reagents. Therefore, electrophilic halogenation reactions of alkenes, alkynes, arenes, heteroarenes, carbonyl compounds, and heteroatoms, as well as radical halogenation involving saturated substrates and in situ halogenated intermediates for Appel-type reactions are presented and discussed. Remarkably, applications of trihaloisocyanuric acids in processes for the construction of heteroarene scaffolds based on electrophilic halo- and oxidative cyclization, multicomponent reactions, and telescopic reactions are also given.

Genetically engineered electrospinning contributes to spinal cord injury repair by regulating the immune microenvironment.

Introduction: Spinal cord injury (SCI) is associated with microenvironment imbalance, thereby resulting in poor regeneration and recovery of the spinal cord. Gene therapy can be used to balance the inflammatory response, however target genes cannot exist in localized injured areas. Methods: A genetically engineered electrospun scaffold (GEES) to achieve long-term immunoregulation and nerve repair was constructed. By combining the microfluidic and electrospinning techniques, interleukin-10 plasmid (pIL10) was loaded into lipid nanoparticles (LNPs) (pIL10-LNP), which was encapsulated to the nerve growth factor (NGF). Immunofluorescence staining, qRT-PCR, ELISA, flow cytometry, and other tests were employed to comprehensively assess the role of GEES in modulating macrophage polarization and facilitating neural repair. Results: The results showed that the scaffold released >70% of the pIL10-LNP within 10 d and continued slow release within 30 d. In vitro cell experiments have demonstrated that GEES effectively stimulates macrophages to secrete anti-inflammatory cytokines and facilitates the differentiation of neural stem cells into neuronal cells. In rat T9 SCI model, the GEES significantly inhibited the inflammatory response in the acute and chronic phases of SCI by transfecting local tissues with slow-release pIL10-LNP to promote the release of the anti-inflammatory factor IL10, thereby creating a favorable microenvironment. With the addition of NGF, the repair and regeneration of nerve tissues was effectively promoted, and the post-SCI motor function of rats improved. Discussion: GEES can regulate post-SCI immune responses through continuous and effective gene delivery, providing a new strategy for the construction of electrospun scaffolds for nerve repair in gene therapy.

Application and Development of Electrospun Nanofiber Scaffolds for Bone Tissue Engineering.

Nanofiber scaffolds have gained significant attention in the field of bone tissue engineering. Electrospinning, a straightforward and efficient technique for producing nanofibers, has been extensively researched. When used in bone tissue engineering scaffolds, electrospun nanofibers with suitable surface properties promote new bone tissue growth and enhance cell adhesion. Recent advancements in electrospinning technology have provided innovative approaches for scaffold fabrication in bone tissue engineering. This review comprehensively examines the utilization of electrospun nanofibers in bone tissue engineering scaffolds and evaluates the relevant literature. The review begins by presenting the fundamental principles and methodologies of electrospinning. It then discusses various materials used in the production of electrospun nanofiber scaffolds for bone tissue engineering, including natural and synthetic polymers, as well as certain inorganic materials. The challenges associated with these materials are also described. The review focuses on novel electrospinning techniques for scaffold construction in bone tissue engineering, such as multilayer nanofibers, multifluid electrospinning, and the integration of electrospinning with other methods. Recent advancements in electrospinning technology have enabled the fabrication of precisely aligned nanofiber scaffolds with nanoscale architectures. These innovative methods also facilitate the fabrication of biomimetic structures, wherein bioactive substances can be incorporated and released in a controlled manner for drug delivery purposes. Moreover, they address issues encountered with traditional electrospun nanofibers, such as mechanical characteristics and biocompatibility. Consequently, the development and implementation of novel electrospinning technologies have revolutionized scaffold fabrication for bone tissue engineering.

A 3D-printable gelatin/alginate/ε-poly-l-lysine hydrogel scaffold to enable porcine muscle stem cells expansion and differentiation for cultured meat development

The mass proliferation of seed cells and imitation of meat structures remain challenging for cell-cultured meat production. With excellent biocompatibility, high water content and porosity, hydrogels are frequently-studied materials for anchorage-dependent cell scaffolds in biotechnology applications. Herein, a scaffold based on gelatin/alginate/ε-Poly-l-lysine (GAL) hydrogel is developed for skeletal muscle cells, which has a great prospect in cell-cultured meat production. In this work, the hydrogel GAL-4:1, composed of gelatin (5 %, w/v), alginate (5 %, w/v) and ε-Poly-l-lysine (molar ratio vs. alginate: 4:1) is selected as cell scaffold based on Young's modulus of 11.29 ± 1.94 kPa, satisfactory shear-thinning property and suitable porous organized structure. The commercially available C2C12 mouse skeletal myoblasts and porcine muscle stem cells (PMuSCs), are cultured in the 3D-printed scaffold. The cells show strong ability of attachment, proliferation and differentiation after induction, showing high biocompatibility. Furthermore, the cellular bioprinting is performed with GAL-4:1 hydrogel and freshly extracted PMuSCs. The extracted PMuSCs exhibit high viability and display early myogenesis (desmin) on the 3D scaffold, suggesting the great potential of GAL hydrogel as 3D cellular constructs scaffolds. Overall, we develop a novel GAL hydrogel as a 3D-printed bioactive platform for cultured meat research.

Intramolecular Radical Amidooxygenation of Alkenes for the Construction of Pyrrolidinones.

An intramolecular 1,2-amidooxygenation of unactivated alkenes for the construction of the pyrrolidinone scaffold containing a masked 5-hydroxymethyl functionality is reported. γ,δ-Unsaturated N-aryloxyamides react with sodium 2,2,6,6-tetramethylpiperidin-1-olate (TEMPONa) to afford alkoxyaminated pyrrolidinones. The cascade proceeds through reductive amidyl radical generation with TEMPONa, 5-exo cyclization, and TEMPO trapping. No transition metal is required to perform these transformations, and complex (fused, bridged) pyrrolidinones are accessible in moderate to good yields. The product alkoxyamines are readily further converted into ketones and alcohols through either oxidation or reduction.

Residual Stress Mitigation in Perovskite Solar Cells via Butterfly-Inspired Hierarchical PbI2 Scaffold.

Residual stress in metal halide perovskite films intimately affects the photovoltaic figure of merit and longevity of perovskite solar cells. A delicate management of the crystallization kinetics is critical to the preparation of high-quality perovskite films. Only very limited methods, however, are available to regulate the residual stress of a perovskite film in a controllable manner, particularly for a perovskite film fabricated by a two-step method. Here, we demonstrate the construction of a hierarchical PbI2 scaffold inspired by Archaeoprepona demophon butterfly by combining an interlayer guided growth of porous structure and nanoimprinting. The hierarchically structured PbI2 that emulates the physical structure of the butterfly wing scale permits unimpeded permeation of organic amine salts and sufficient space for volume expansion during the crystallization process, accompanied by preferential perovskite growth of a defectless (001) crystal plane. The optimized perovskite film outperforms the control with reduced residual stress and defect density. Consequently, perovskite solar cells with a respectable power conversion efficiency reaching 23.4% (certified 23%) and an impressive open-circuit voltage of 1.184 V can be achieved. The target device can maintain 80% of initial efficiency after maximum power point tracking under illumination for 700 h. This work expands the range of engineering toward PbI2 by exploring a simultaneously tailored morphology and crystallinity and highlights the significance of a hierarchical PbI2 scaffold as an alternative choice to mitigate residual stress in a two-step processed perovskite active layer and boost the longevity of perovskite solar cells.

Fluorene and Fluorenone Unnatural Amino Acid Motifs via Diastereoselective Pd(II)‐Catalyzed sp3C−H Functionalization

AbstractThis paper reports the construction of racemic and enantiopure (D‐ and L‐) fluorene and fluorenone‐based novel unnatural amino acid derivatives. The Pd(II)‐catalyzed bidentate directing group‐aided arylation of prochiral β‐C(sp3)‐H bonds in racemic, enantiopure carboxamides of amino acids with iodofluorenes was reported. The construction of novel examples of fluorene and fluorenone motifs containing amino acids comprising of norvaline, leucine, phenylalanine, norleucine, 2‐aminooctanoic acid derivatives having the anti‐stereochemistry (with good enantiopurity) was accomplished. The construction of bis fluorenyl alanine scaffolds and fluorenyl motif‐containing non‐α‐amino acid (aminoalkanoic acid) derivatives was also reported. Examples of removal of the directing group (8‐aminoquinoline) and phthalimide‐protecting group present in the fluorenyl‐based unnatural amino acid derivatives have been shown. Accordingly, fluorene motif‐based amino acid esters and free amino group‐containing unnatural amino acid derivatives were synthesized. The stereochemistry of the major (anti) diastereomers obtained via the prochiral β‐C(sp3)‐H arylation of norvaline, leucine, phenylalanine, norleucine, 2‐aminooctanoic acid derivatives was ascertained from the X‐ray structure of a representative compound. Fluorene‐ and fluorenone‐based motifs are vital skeletons in materials and medicinal chemistry research. Accordingly, this work is a contribution towards enriching the library of fluorene and fluorenone unnatural amino acid scaffolds.

Pyrazolidinone-Aided Ru(II)-Catalyzed Regioselective C-H Annulation with Allenes.

Regioselective annulation of allenes via C-H activation represents an elegant synthetic approach toward the construction of valuable scaffolds. Considering the importance of allenes, herein we developed an unprecedented Ru(II)-catalyzed highly regioselective redox-neutral C-H activation/(4 + 1)-annulation of 1-arylpyrazolidinones employing allenyl acetates to access pyrazolo[1,2-a]indazol-1-one derivatives. Additionally, allenyl cyclic carbonates, which were never tested in C-H activation, were utilized to construct a similar class of heterocycles having a pendent alcohol functionality. Notably, double C-H functionalization was achieved by a simple modification of reaction conditions. The synthetic significance of this methodology is underscored by late-stage modification of natural products, broad substrate scope, gram-scale synthesis, and postfunctionalizations.

PolyBorylated Alkenes as Energy-Transfer Reactive Groups: Access to Multi-Borylated Cyclobutanes Combined with Hydrogen Atom Transfer Event.

While polyborylated alkenes are being recognized for their elevated status as highly valuable reagents in modern organic synthesis, allowing efficient access to a diverse array of transformations, including the formation of C-C and C-heteroatom bonds, their potential as energy-transfer reactive groups has remained unexplored. Yet, this potential holds the key to generating elusive polyborylated biradical species, which can be captured by olefins, thereby leading to the construction of new highly-borylated scaffolds. Herein, we report a designed energy-transfer strategy for photosensitized [2+2]-cycloadditions of poly-borylated alkenes with various olefins enabling the regioselective synthesis of diverse poly-borylated cyclobutane motifs, including the 1,1-di-, 1,1,2-tri-, and 1,1,2,2-tetra-borylated cyclobutanes. In fact, these compounds belong to a family that presently lacks efficient synthetic pathways. Interestingly, when α-methylstyrene was used, the reaction involves an interesting 1,5-hydrogen atom transfer (HAT). Mechanistic deuterium-labeling studies have provided insight into the outcome of 1,5-hydrogen atom transfer process. In addition, the polyborylated cyclobutanes are then demonstrated to be useful in selective oxidation processes resulting in the formation of cyclobutanones and γ-lactones.

Flexural Performance of Steel–Normal Concrete–Ultra-High-Performance Concrete Composite Slabs with Steel Ribs

For steel–concrete composite bridges, the cracking of concrete in the tensile zone influences the serviceability of bridges and decreases their durability. UHPC, as a high-tensile and -durability material, is used to replace a part of the concrete to enhance the tensile performance. Thus, the steel–normal concrete–UHPC composite slab, as a new composite structure, is formed. This paper investigates the flexural behaviours of steel–normal concrete–UHPC composite slabs through a full-scale experiment, numerical simulation, and theoretical analysis. The research results indicate that (1) UHPC enhances the flexural performance of the tensile zone and delays the development of cracks. The initial cracking force of concrete increases from 44 kN to 91 kN. (2) UHPC effectively enhances the carrying capacity of composite slabs. A 50 mm UHPC layer makes the flexural bearing capacity of steel–concrete composite slabs increase by 13.51%. (3) The construction methods influence the initial cracking force of composite slabs. For full-span scaffolding construction, the initial cracking force decreases from 91 kN to 69 kN compared with construction without brackets. (4) The theoretical model considering the tensile contribution of cracking UHPC can accurately predict the bearing capacity of the composite slabs. And the theoretical values of the bearing capacity are lower than the experimental values, which makes the composite slabs safer in service.

Chitosan-Chitosan derivative for cartilage associated disorders: Protein interaction and biodegradability

Chitosan is a well-known biomaterial in the field of cartilage tissue engineering because of its flexibility. The construction of chitosan-based scaffolds is reviewed in several production methods, including freeze-drying, gelation, salt leaching, and electrospinning. In this review, many benefits of chitosan are discussed, including the interaction of chitosan with other materials and their effects, its adaptability, high reproducibility, biocompatibility, role in cellular differentiation, interactions with TGF-β (transforming growth factor-β), protein interactions, biodegradability, influencing osteoblast expression, and potential for treating bone diseases. The study also provides information on how mathematical models are used to analyze how MSC (mesenchymal stem cells) and chondrocyte distribution in multilayer hydrogels change in response to TGF-β diffusion. Results showed that collagen has weak mechanical properties and easily disintegrates during bone tissue formation, it is difficult to use alone as a biomaterial, and new scaffolds made of whey protein isolate (WPI) and chitosan may help repair osteochondral tissue. However, the thorough analysis reveals chitosan's crucial contribution to the development of cartilage tissue engineering as well as its potential to address issues in the field.

Liquid nitrogen improves the decellularization effectiveness of whole-ovary

BACKGROUND: Ovarian tissue cryopreservation for fertility preservation carries a risk of malignant cell re-seeding. Artificial ovary is a promising method to solve such a problem. However, ovary decellularization protocols are limited. Hence, further studies are necessary to get better ovarian decellularization techniques for the construction of artificial ovary scaffolds. OBJECTIVE: To establish an innovative decellularization technique for whole porcine ovaries by integrating liquid nitrogen with chemical agents to reduce the contact time between the scaffolds and chemical reagents. MATERIALS AND METHODS: Porcine ovaries were randomly assigned to three groups: novel decellularized group, conventional decellularized group and fresh group. The ovaries in the novel decellularized group underwent three cycles of freezing by liquid nitrogen and thawing at temperatures around 37??C before decellularization. The efficiency of the decellularization procedure was assessed through histological staining and DNA content analysis. The maintenance of ovarian decellularized extracellular matrix(ODECM) constituents was determined by analyzing the content of matrix proteins. Additionally, we evaluated the biocompatibility of the decellularized extracellular matrix(dECM) by observing the growth of granulosa cells on the ODECM scaffold in vitro.RESULTS: Hematoxylin and eosin staining, DAPI staining and DNA quantification techniques collectively confirm the success of the novel decellularization methods in removing cellular and nuclear components from ovarian tissue. Moreover, quantitative assessments of ODECM contents revealed that the novel decellularization technique preserved more collagen and glycosaminoglycan compared to the conventional decellularized group (P<0.05). Additionally, the novel decellularized scaffold exhibited a significantly higher number of granulosa cells than the conventional scaffold during in vitro co-culture (P<0.05). CONCLUSION: The novel decellularized method demonstrated high efficacy in eliminating DNA and cellular structures while effectively preserving the extracellular matrix. As a result, the novel decellularized method holds significant promise as a viable technique for ovarian decellularization in forthcoming studies.

Potential use of a bone tissue engineering scaffold based on electrospun poly (ɛ-caprolactone) - Poly (vinyl alcohol) hybrid nanofibers containing modified cockle shell nanopowder

Today, the construction of scaffolds promoting the differentiation of stem cells is an intelligent innovation that accelerates the differentiation toward the target tissue. The use of calcium and phosphate compounds is capable of elevating the precision and efficiency of the osteogenic differentiation of stem cells. In this research, osteoconductive electrospun poly (ɛ-caprolactone) (PCL) - poly (vinyl alcohol) (PVA) hybrid nanofibrous scaffolds containing modified cockle shell (CS) nanopowder were prepared and investigated. In this regard, the modified CS nanopowder was prepared by grinding and modifying with phosphoric acid, and it was then added to PVA nanofibers at different weight percentages. Based on the SEM images, the optimum content of the modified CS nanopowder was set at 7 wt %, since reaching the threshold of agglomeration restricted this incorporation. In the second step, the PVA-CS7 nanofibrous sample was hybridized with different PCL ratios. Concerning the hydrophilicity and mechanical strength, the sample named PCL50-PVA50-CS7 was ultimately selected as the optimized and suitable candidate scaffold for bone tissue application. The accelerated hydrolytic degradation of the sample was also studied by FTIR and SEM analyses, and the results confirmed that the mineral deposits of CS are available approximately 7 days for mesenchymal stem cells. Moreover, Alizarin red staining illustrated that the presence of CS in the PCL50-PVA50-CS7 hybrid nanofibrous scaffold may potentially lead to an increase in calcium deposits with high precipitates, authenticating the differentiation of stem cells towards osteogenic cells.

Absorbable Biosynthetic Scaffolds in Place of Silicone for Breast Reconstruction: A 9-Year Experience with 53 Patients

Background: Few series report on using fat grafting as the primary form of breast reconstruction. A 9-year experience with absorbable biosynthetic scaffolds, used in place of silicone implants, for breast reconstruction is reviewed. Methods: A clinical quality improvement approach was used to evaluate real-world data on a single plastic surgeon’s experience treating breast reconstruction patients over a 7-year period. Results: Fifty-three patients had 74 breasts reconstructed, (following 51 therapeutic mastectomies and 23 prophylactic). Five of the 51 breasts (9.80 %) developed a local recurrence (mean follow-up of 4.5–5.5 years). This compared favorably with the practice’s previous 6 years of silicone reconstructions. The most common complications were benign fat necrosis and oil cysts. More than 100 radiologic examinations were performed without interference by the absorbable implants. By 12–18 months post implantation, very little immune response was seen on histologic examinations of the biosynthetic scaffold constructs. Mature collagen and robust vascularity characterized the “mesh zone,” whereas regenerated adipose tissue was seen in between and on top of the folded sheets of the implants. The average number of fat graft sessions in immediate reconstructions was 2.3, with a mean total fat graft volume of 551 mL, to restore an average mastectomy defect volume of 307 mL. Aesthetic outcomes were much better in the immediate reconstruction of nipple-sparing mastectomy group, which saw 68% achieve an A/B grade; 19%, C grade; and 13%, D/F on subjective grading. Conclusion: This composite strategy, using biosynthetic scaffold and autologous fat grafting, yielded outcomes equivalent to flap reconstructions with the ease of implants.

Use of negative thermal expansion to design scaffolds for cultured meat

Additive manufacturing is proposed as a novel tool to produce complex scaffold constructs for use in cell cultured meat. The presence of scaffolds in the final cell cultured products raises the need to understand the thermal behavior of biopolymers through culturing and cooking as it relates to the final organoleptic properties. Therefore, the objective of this study was to understand how aqueous and high temperature environments influence plasticization and contraction of biopolymer scaffolds through the physio–chemical mechanisms of hydrolysis and negative thermal expansion. To achieve this objective, scaffolds were printed using a negative thermal expansion stretch–dominated design in both PLA and PLA-TPU material configurations. The samples were evaluated after a simulated cooking experiment (90 °C for 10 mins). The formation of crystals in the single material PLA during cooking led to bend–dominated contraction while the dual-material PLA-TPU experienced stretch–dominated contraction. Furthermore, exceeding the glass transition temperature of PLA during simulated cooking in an aqueous environment caused irreversible deformation to the scaffold structure that has the potential to influence organoleptic properties.