Stable Scaffold Research Articles

In-situ growth of hierarchical N-doped CNTs/Ni Foam scaffold for dendrite-free lithium metal anode

Practical application of lithium metal (Li) anodes is impeded by Li dendrites generated by nonuniform deposition, which always leads to severe safety hazards. Herein, a stable hierarchical scaffold is rationally designed for dendrite-free lithium metal anode (LMA). The hierarchical scaffold consists of in-situ grown N-doped carbon nanotubes on the porous Ni foam (NCNT/NF), in which the interconnected NCNTs form the secondary structure and render numerous nucleation sites for uniform Li deposition. When applied as the Li metal anode, the NCNT/NF exhibits dendrite-free morphology without serial cracks and dead Li deposition whether it is treated by direct Li deposition or by infusing molten Li into the well-designed lithiophilic structure. Particularly, the hierarchical NCNT/NF scaffold shows low overpotential and high coulombic efficiency (average 98.2% over 200 cycles at 1 ​mA ​cm−2) during Li stripping/plating process. Furthermore, an ultralong life span over 400 ​h ​at 3 ​mA ​cm−2 with high areal capacity of 3 ​mA ​h cm−2 and stable full cell performance coupled with LiFePO4 (capacity retention of 94% after 400 cycles at 2C) can be achieved by NCNT/NF/Li composite anode. This is attributed to the rational design of NCNT/NF scaffold, which combines both the merits of hierarchical framework and excellent Li affinity from N-rich species (pyridinic N and pyrrolic N).

Regulation and function of SOX9 during cartilage development and regeneration.

Chondrogenesis is a highly coordinated event in embryo development, adult homeostasis, and repair of the vertebrate cartilage. Fate decisions and differentiation of chondrocytes accompany differential expression of genes critical for each step of chondrogenesis. SOX9 is a master transcription factor that participates in sequential events in chondrogenesis by regulating a series of downstream factors in a stage-specific manner. SOX9 either works alone or in combination with downstream SOX transcription factors, SOX5 and SOX6 as chondrogenic SOX Trio. SOX9 is reduced in the articular cartilage of patients with osteoarthritis while highly maintained during tumorigenesis of cartilage and bone. Gene therapy using viral and non-viral vectors accompanied by tissue engineering (scaffolds) is a promising tool to regenerate impaired cartilage. Delivery of SOX9 or chondrogenic SOX Trio into cells produces efficient therapeutic effects on chondrogenesis and this event is facilitated by scaffolds. Non-viral vector-guided delivery systems encapsulated or loaded in mechanically stable solid scaffolds are useful for the regeneration of articular cartilage. Here we review major milestones and most recent studies focusing on regulation and function of chondrogenic SOX Trio, during chondrogenesis and cartilage regeneration, and on the development of advanced technologies in gene delivery with tissue engineering to improve efficiency of cartilage repair process.

Double Approach Towards 3D Electrodeposited RuOx Porous Structure for High Energy/High Power Micro-Supercapacitors

Hydrous RuOx has been one of the well-studied materials for application in supercapacitors owing to its excellent properties (high conductivity similar to metals, redox activity capable of fast faradaic reactions and structural water enabling swift proton transfer and decreased diffusion distance). The main issue regarding supercapacitors is that, they suffer from low energy density compared to batteries. One way to overcome this problem is to increase surface area of the active material and hence the energy stored through 3D structuration of current collector. Multiple techniques have been used in this regard like 3D printing, pholitography methods...etc. However, these techniques are pretty complex, time consuming and have constraining conditions. Hence, it’s necessary to develop economic and simple routes for 3D structuration of electrodes for micro-supercapacitors. One simple, time efficient and easy to set up method that can be used under ambient conditions is the electrochemical structuration using dynamic hydrogen bubble template (DHBT). With this strategy, 3D scaffolds which can hold small quantities of intrinsic pseudocapacitve materials like RuOx can be fabricated. The challenge in this latter case is magnified, needing controlled decoration of active materials for efficient utilization and full benefit of the 3D framework. Hence, the pursuit of superior micro-supercapacitors not only needs controlled deposition, but also requires stable 3D scaffolds to maximize capacitance per footprint area1. We have previously shown electrodeposition of active RuOx on porous gold electrodes for micro-supercapacitors achieving a capacitance of 3 F/cm².2 One other approach would be to deposit the active material directly by the DHBT method. As RuOx is a good conductor this would not hinder its efficiency (this would not be the case for MnO2 for example). The difficulty here is that, not all metals can be deposited by the DHBT technique as other factors play a crucial role such as the exchanged current density towards H2 evolution and mechanical stability3. In the current work, we report two different strategies for the 3D deposition of RuOx. The first is the successful fabrication of highly porous 3D platinum current collector using DHBT followed by a conformal coating of hydrous RuOx to achieve a specific capacitance as high as 7 F/cm². The second is the direct electrodeposition of the active material, RuOx, in a 3D porous structure. These two approaches are characterized and discussed within the framework of fabricating superior micro-supercapacitors with excellent capacitance and low internal resistance.

Rigid-Flexible Coupling Carbon Skeleton and Potassium-Carbonate-Dominated Solid Electrolyte Interface Achieving Superior Potassium-Ion Storage

Potassium-ion energy-storage devices are highly attractive in the large-scale energy storage field, but the intercalation of large K ions greatly worsens the stability of electrode structures and solid electrolyte interphase (SEI) films, causing slow reaction dynamics and poor durability. In this Article, inspired by bubble wraps in our life, a bubble-wrap-like carbon sheet (BPCS) with a rigid-flexible coupling porous architecture is fabricated on the microscale, exhibiting strong structural stability and good accommodation for volume expansion. In the meantime, a K2CO3·1.5H2O-dominated SEI is created by an interfacial transfer behavior of carbonate groups. These K2CO3·1.5H2O nanograins not only enhance the stability of the SEI by constructing a stable scaffold but also create more diffusion routes for K ions. On the basis of the above, using the BPCS as the anode of potassium-ion batteries delivers reversible capacities of 463 mAh g-1 at 50 mA g-1 and 195 mAh g-1 at 10 A g-1 with a long cycling life. The assembled BPCS//NPC potassium-ion hybrid capacitor exhibits a high energy density of 167 Wh kg-1 and a superior cycling capability with 80.8% capacity retention over 10 000 cycles with nearly 100% Coulombic efficiency. Even at the higher current density of 10 A g-1, the device could deliver an energy density of 92.9 Wh kg-1 over 5000 cycles at a power density of 9200 W kg-1 with only 0.002% fading per cycle, which can rival lithium-ion hybrid supercapacitors.

Investigation into the Metabolic Limitations of Alpha Conotoxins as Drugs in the Gastrointestinal Tract

Peptides isolated from cone snails, known as conotoxins, have potential in treating neuropathic pain. Peptides often lack efficacy as drugs due to poor pharmacokinetic profiles despite displaying high potency and selectivity. Conotoxins present significant sequence diversity, but little information exists about their pharmacokinetic properties. We hypothesize that this diversity will correlate with dynamic pharmacokinetic profiles, with some peptides exhibiting increased stability. In this study, we aimed to gain a basic understanding of the stability of the conotoxins α‐IMI and α‐GI in the stomach and intestines. Both have different primary sequences despite serving as antagonists of the acetylcholine receptor, which is a potential target in cancer, chemotherapy‐induced allodynia and possibly pain associated with Crohn’s disease. In order to study these peptides, novel mass spectrometry (LC‐MS/MS) methods were developed incorporating multiple reaction monitoring scans for each peptide in simulated gastric and intestinal fluids. The quantitation range of our method was 0.5–5 μg/mL, which is 20 times more sensitive than traditional methods. To compare gastrointestinal metabolic stability, each peptide was incubated in simulated gastric fluid and intestinal fluid and their stability was measured using our LC‐MS/MS method at times ranging from 0–90 minutes. Both peptides displayed a high amount of stability in gastric fluid, as no significant loss of either peptide was determined after 90 minutes. In intestinal fluid IMI degraded rapidly (t1/2= ~6 minutes), whereas α‐GI displayed far more stability in the same environment (t1/2= ~257 minutes). α‐GI incorporates a prominent helix in its structure which is likely responsible for its increased stabilization in comparison to IMI. Considering the differences in the metabolic stability of these peptides, further study of conotoxin sequences may result in the identification of stable molecular scaffolds. In the future, we plan to pinpoint what particular features are responsible for metabolic stability or susceptibility across more conotoxins, such as differences in sequence, structure and rigidity and plan to use this information to produce analogs with increased stability within the gastrointestinal tract.Support or Funding InformationSource of Research Support: This work was supported by the Pacific University Research Incentive Grant Program and an ASPET Summer Undergraduate Research Fellowship (SURF) award at Pacific University.

Versican-A Critical Extracellular Matrix Regulator of Immunity and Inflammation.

The extracellular matrix (ECM) proteoglycan, versican increases along with other ECM versican binding molecules such as hyaluronan, tumor necrosis factor stimulated gene-6 (TSG-6), and inter alpha trypsin inhibitor (IαI) during inflammation in a number of different diseases such as cardiovascular and lung disease, autoimmune diseases, and several different cancers. These interactions form stable scaffolds which can act as “landing strips” for inflammatory cells as they invade tissue from the circulation. The increase in versican is often coincident with the invasion of leukocytes early in the inflammatory process. Versican interacts with inflammatory cells either indirectly via hyaluronan or directly via receptors such as CD44, P-selectin glycoprotein ligand-1 (PSGL-1), and toll-like receptors (TLRs) present on the surface of immune and non-immune cells. These interactions activate signaling pathways that promote the synthesis and secretion of inflammatory cytokines such as TNFα, IL-6, and NFκB. Versican also influences inflammation by interacting with a variety of growth factors and cytokines involved in regulating inflammation thereby influencing their bioavailability and bioactivity. Versican is produced by multiple cell types involved in the inflammatory process. Conditional total knockout of versican in a mouse model of lung inflammation demonstrated significant reduction in leukocyte invasion into the lung and reduced inflammatory cytokine expression. While versican produced by stromal cells tends to be pro-inflammatory, versican expressed by myeloid cells can create anti-inflammatory and immunosuppressive microenvironments. Inflammation in the tumor microenvironment often contains elevated levels of versican. Perturbing the accumulation of versican in tumors can inhibit inflammation and tumor progression in some cancers. Thus versican, as a component of the ECM impacts immunity and inflammation through regulating immune cell trafficking and activation. Versican is emerging as a potential target in the control of inflammation in a number of different diseases.

Self-Assembled Multivalent Aptamer Nanoparticles with Potential CAR-like Characteristics Could Activate T Cells and Inhibit Melanoma Growth

In this study, the CAR-like multivalent aptamer nanoparticles (X-polymers) were assembled with the dimer of murine CD28 RNA aptamer (CD28Apt7), the tetramer of CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) RNA aptamer (Del60), and a folic acid labeled ssDNA fragment in a stable nucleic acid three-way junction scaffold (3WJ). Results showed that the X-polymers could recognize both the mCD28 and mCTLA-4 molecules. Confocal imaging and flow cytometry assays showed that the X-polymers could target both T cells and B16 cells in vitro. With the first costimulatory signals provided by the CD3 antibodies, the X-polymers could increase T cell proliferation and reverse the inhibitory effect of interleukin-2 (IL-2) secreting caused by exogenous B7.1 molecules on T cells in vitro. Results of our study also showed that X-polymers could inhibit mouse melanoma B16 cell growth both in vitro and in vivo. Our study demonstrated for the first time that the multivalent aptamer nanoparticle-activated T cells could fulfill the function of CAR-T, which promised a novel approach to developing a multi-functional design of aptamer drugs with potential CAR-like characteristics to enhance the safety of CAR-T cell immunotherapy.

Selective Carboxylate Recognition Using Urea-Functionalized Unclosed Cryptands: Mild Synthesis and Complexation Studies.

Herein we present the synthesis and evaluation of anion-binding properties of 12 new receptors from the unclosed cryptand family. Their core is built on the stable 26-membered tetraamidic macrocyclic scaffold, whereas various alkyl and aryl urea substituents were introduced after a yield-limiting macrocyclization step (65–98%). The receptors strongly bind anions, in particular carboxylates, even in a highly competitive solvent mixture (DMSO-d6 + H2O 95:5 v/v).

Modification of an Anopheles gambiae odorant binding protein to create an array of chemical sensors for detection of drugs

The binding pockets of odorant binding proteins from Anopheles gambiae (OBP1 and OBP47) were analysed using in silico modelling. The feasibility of creating mutant proteins to achieve a protein array capable of detecting drugs of abuse in solution or in vapour phase was investigated. OBP1 was found to be easily adapted and several mutant proteins were expressed and characterised. AgamOBP1_S82P was found to have high affinities to cannabinol, 3,4-methylenedioxy methamphetamine (MDMA/Ecstasy) and cocaine hydrochloride. When these proteins were immobilised on a quartz crystal microbalance, saturated cocaine hydrochloride vapour could be detected. The sensors were stable over a period of at least 10 months in air. The approach taken allows flexible design of new biosensors based on inherently stable protein scaffolds taking advantage of the tertiary structure of odorant binding proteins.

Intra-locked G-quadruplex structures formed by irregular DNA G-rich motifs.

G-rich DNA sequences with tracts of three or more continuous guanines (G≥3) are known to have high propensity to adopt stable G-quadruplex (G4) structures. Bioinformatic analyses suggest high prevalence of G-rich sequences with short G-tracts (G≤2) in the human genome. However, due to limited structural studies, the folding principles of such sequences remain largely unexplored and hence poorly understood. Here, we present the solution NMR structure of a sequence named AT26 consisting of irregularly spaced G2 tracts and two isolated single guanines. The structure is a four-layered G4 featuring two bi-layered blocks, locked between themselves in an unprecedented fashion making it a stable scaffold. In addition to edgewise and propeller-type loops, AT26 also harbors two V-shaped loops: a 2-nt V-shaped loop spanning two G-tetrad layers and a 0-nt V-shaped loop spanning three G-tetrad layers, which are named as VS- and VR-loop respectively, based on their distinct structural features. The intra-lock motif can be a basis for extending the G-tetrad core and a very stable intra-locked G4 can be formed by a sequence with G-tracts of various lengths including several G2 tracts. Findings from this study will aid in understanding the folding of G4 topologies from sequences containing irregularly spaced multiple short G-tracts.

3D hierarchical CoFe2O4/CoOOH nanowire arrays on Ni-Sponge for high-performance flexible supercapacitors

Human activities-enabled mechanical energy as one of the clean energy sources can be stored and used to power electronics. However, there are still lacks of ways to effectively collect and store the human activities-involved mechanical energy. Supercapacitor has been regarded as the most promising solution for this challenge. In this work, CoOOH nanowires were in-situ grown on Ni sponges (NS) with CoFe2O4 nanolayer by a simple hydrothermal method followed with thermal deposition to prepare supercapacitor electrode. Very interestingly, compared with CoOOH nanowires directly grow on bare NS, the CoOOH nanowires grow on the CoFe2O4 nanolayers demonstrated more stable microstruture, which interconnected with each other to form a stable three-dimensional scaffold that can ensure sufficient exposure of the active sites to the electrolyte. When used as supercapacitor electrode, the NS/CoFe2O4/CoOOH electrode showed ultrahigh specific capacity (200.3 mA h g−1 at 1 mA g−1) and excellent cycling stability (92.7% after 2000 cycles at 1 mA g−1). The asymmetric electrochemical energy storage device is assembled with NS/CoFe2O4/CoOOH as anode and reduced graphene oxide (rGO) polymer composite foam as cathode, which can deliever an energy density of 54.1 W h kg−1 at a power density of 374.9 W kg−1. Furthermore, a mechanical generator was used to charge the assembled flexible supercapacitor, which demonstrated an average conversion rate of 84% from mechanical energy charging voltage. A fully charged flexible supercapacitor can drive a toy carmore than 5 m, indicating huge potentiol of the assmebled supercapator for mechanical energy storage.

Biomass-derived carbon from Ganoderma lucidum spore as a promising anode material for rapid potassium-ion storage

The design and preparation of powerful anode materials are key to developing potassium-ion batteries. A biomass-based potassium anode material with a distinct hollow-cage structure was prepared by one-step carbonization. The target carbon exhibited a specific surface area of 104.4 m2 g−1 and mesopores/macropores distributed materials. When used as the negative electrode of a potassium-ion battery, the cage-like porous carbon (CPC) showed a reversible capacity of 407 mAh g−1 after 50 cycles at 50 mA g−1 current density. After 100 cycles, at a current density of 200 mA g−1, the reversible capacity was 163.8 mAh g−1. It still exhibits an extremely long cycle stability at high current densities (discharge capacity of 124.6 mAh g−1 after 700 cycles at a current density of 1 A g−1). The excellent performance is attributed to the stable cage-like carbon scaffold and uniform continuous distribution of mesopores/macropores to improve ion diffusion kinetics and electronic conductivity. These results indicate that a properly designed CPC can effectively increase the capacity and cycle stability of a potassium-ion battery.

Injectable Microannealed Porous Scaffold for Articular Cartilage Regeneration.

The purpose of this study is to assess the feasibility of a novel microporous annealed particle (MAP) scaffolding hydrogel to enable both articular cartilage and subchondral bone biointegration and chondrocyte regeneration in a rat knee osteochondral defect model. An injectable, microporous scaffold was engineered and modified to match the mechanical properties of articular cartilage. Two experimental groups were utilized-negative saline control and MAP gel treatment group. Saline and MAP gel were injected into osteochondral defects created in the knees of Sprague-Dawley rats. Photo-annealing of the MAP gel was performed. Qualitative histologic and immunohistochemical analysis was performed of the treated defects at 2, 4, and 8 weeks postsurgery. The injectable MAP gel successfully annealed and was sustained within the osteochondral defect at each timepoint. Treatment with MAP gel resulted in maintained size of the osteochondral defect with evidence of tissue ingrowth and increased glycosaminoglycan production, whereas the control defects presented with evidence of disorganized scar tissue. Additionally, there was no significant inflammatory response to the MAP gel noted on histology. We have demonstrated the successful delivery of an injectable, flowable MAP gel scaffold into a rat knee osteochondral defect with subsequent annealing and stable integration into the healing wound. The flowable nature of this scaffold allows for minimally invasive application, for example, via an arthroscopic approach for management of wrist arthritis. The MAP gel was noted to fill the osteochondral defect and maintain the defect dimensions and provide a continuous and smooth surface for cartilage regeneration, suggesting its ability to provide a stable scaffold for tissue ingrowth. Future chemical, mechanical, and biological gel modifications may improve objective evidence of cartilage regeneration.

Active loading graphite/hydroxyapatite into the stable hydroxyethyl cellulose scaffold nanofibers for artificial cornea application

The design of biocompatible porous scaffolds that encourage cell adhesion for corneal tissue engineering applications continues to be challenging. In addition to porous hydrogels, nanofibers that can simulate the extracellular matrix structure for cell adhesion would be beneficial. Graphite and nano-hydroxyapatite (nHA) are two bioactive materials that have been used to improve cell adhesion in scaffolds for corneal tissue engineering. In this study, nanofibers were fabricated from hydroxyethyl cellulose and polyvinyl alcohol (PVA) and cross-linked by glutaraldehyde bound to graphite and nano-hydroxyapatite. This scaffold surrounded a transparent hydrogel core from PVA that was cross-linked by freeze-thawing cycles. The chemical and mechanical evaluations demonstrated that nanofibers met the requirements as a scaffold for corneal tissue engineering. The results showed that when the concentration of nHA was approximately 1.66 wt%, the morphology of human epithelial cells did not change, and clot formation occurred around the scaffold during the 1-week in vivo implantation.

Nonmulberry Silk Based Ink for Fabricating Mechanically Robust Cardiac Patches and Endothelialized Myocardium-on-a-Chip Application.

Bioprinting holds great promise towards engineering functional cardiac tissue constructs for regenerative medicine and as drug test models. However, it is highly limited by the choice of inks that require maintaining a balance between the structure and functional properties associated with the cardiac tissue. In this regard, we have developed a novel and mechanically robust biomaterial-ink based on non-mulberry silk fibroin protein. The silk-based ink demonstrated suitable mechanical properties required in terms of elasticity and stiffness (~40 kPa) for developing clinically relevant cardiac tissue constructs. The ink allowed the fabrication of stable anisotropic scaffolds using a dual crosslinking method, which were able to support formation of aligned sarcomeres, high expression of gap junction proteins as connexin-43, and maintain synchronously beating of cardiomyocytes. The printed constructs were found to be non-immunogenic in vitro and in vivo. Furthermore, delving into an innovative method for fabricating a vascularized myocardial tissue-on-a-chip, the silk-based ink was used as supporting hydrogel for encapsulating human induced pluripotent stem cell derived cardiac spheroids (hiPSC-CSs) and creating perfusable vascularized channels via an embedded bioprinting technique. We confirmed the ability of silk-based supporting hydrogel towards maturation and viability of hiPSC-CSs and endothelial cells, and for applications in evaluating drug toxicity.

Potent neutralization of SARS-CoV-2 by human antibody heavy-chain variable domains isolated from a large library with a new stable scaffold

Potent neutralization of SARS-CoV-2 by human antibody heavy-chain variable domains isolated from a large library with a new stable scaffold

Re(η6-arene)2]+ as a highly stable ferrocene-like scaffold for ligands and complexes.

Ferrocenes are versatile ligand scaffolds, complexes of which have found numerous applications in catalysis. Structurally similar but of higher redox stabilites are sandwich complexes of the [Re(η6-arene)2]+ type. We report herein routes for conjugating potential ligands to a single or to both arenes in this scaffold. Since the arene rings can freely rotate, the [Re(η6-arene)2]+ has a high degree of structural flexibility. Polypyridyl ligands were successfully introduced. The coordination of Co(ii) to such a model tetrapyridyl-Re(i)-bis-benzene complex produced a bimetallic Re(i)-Co(ii) complex. To show the stability of the resulting architecture, a selected complex was subjected to photocatalytic reactions. It showed good activity in proton reduction over a long time and did not decompose, corroborating its extraordinary stability even under light irradiation. Its activity compares well with the parent catalyst in turn over numbers and frequencies. The supply of electrons limits catalytic turnover frequency at concentrations below ∼10 μM. We also show that other ligands can be introduced along these strategies. The great diversity offered by [Re(η6-arene)2]+ sandwich complexes from a synthetic point allows this concept to be extended to other catalytic processes, comparable to ferrocenes.

Three-dimensional bioprinting using a coaxial needle with viscous inks in bone tissue engineering - An In vitro study

Introduction:Vascularized autologous tissue grafts are considered “gold standard” for the management of larger bony defects in the craniomaxillofacial area. This modality does however carry limitations, such as the absolute requirement for healthy donor tissues and recipient vessels. In addition, the significant morbidity of large bone graft is deterrent to fibula bone flap use. Therefore, less morbid strategies would be beneficial. The purpose of this study was to develop a printing method to manufacture scaffold structure with viable stem cells.Materials and Methods:In total, three different combinations of ground beta tri-calcium phosphate and CELLINK (bioinks) were printed with a nozzle to identify a suitable bioink for three-dimensional printing. Subsequently, a coaxial needle, with three different nozzle gauge combinations, was evaluated for printing of the bioinks. Scaffold structures (grids) were then printed alone and with additional adipose stem cells before being transferred into an active medium and incubated overnight. Following incubation, grid stability was evaluated by assessing the degree of maintained grid outline, and cell viability was determined using the live/dead cell assay.Results:Among the three evaluated combinations of bioinks, two resulted in good printability for bioprinting. Adequate printing was obtained with two out of the three nozzle gauge combinations tested. However, due to the smaller total opening, one combination revealed a better stability. Intact grids with maintained stability were obtained using Ink B23 and Ink B42, and approximately 80% of the printed stem cells were viable following 24 hours.Discussion:Using a coaxial needle enables printing of a stable scaffold with viable stem cells. Furthermore, cell viability is maintained after the bioprinting process.

Aerogel from fruit biowaste produces ultracapacitors with high energy density and stability

Abstract Biomass waste from jackfruit and durian were used to produce carbon aerogel electrodes incorporating stable scaffolding of base material and natural nitrogen doping. Higher atomic doping of nitrogen in DCA (durian carbon aerogel) compared to JCA (jackfruit carbon aerogel) indicates preservation of nitrogen-containing functional groups during the synthesis. The specific surface area and proportion of mesopores is greater for DCA than for JCA samples. Electrochemical characterizations via cyclic voltammetry, galvanotactic charge discharge and electrochemical impedance spectroscopy show high specific capacitance for both DCA (591 F g−1) and JCA (292 F g−1) at 1 A g−1 current density with two-electrode configuration with excellent cycling stability and charge.

Visualization of the Stimuli-responsive Surface Behavior of Functionalized Wood Material by Chemical Force Microscopy

The hierarchical and porous wood structure provides a stable scaffold to design functionalized lignocellulosic materials with extended properties by chemical modification techniques. However, proper nanoscale characterization methods for these novel materials are needed to confirm the presence of the added functionality and to locate the introduced functional groups with high spatial resolution. Chemical force microscopy is a suitable characterization method to distinguish chemical surface characteristics by scanning the samples surface with a functionalized tip. We report the application of this nanotechnology method on both, unmodified and functionalized wood samples to confirm the thermo-responsive behavior of poly(N-isopropylacrylamide) (PNIPAM) modified spruce wood. By performing force measurements on ultra-microtomed surfaces, adhesion force differences on the analysed structure are monitored and reveal the location and functionality of introduced functional groups. The modified samples are scanned below and above their lower critical solution temperature with a hydrophobic tip in aqueous media to observe adhesion changes. Additionally, confocal Raman microscopy support the chemical force microscopy measurements by revealing the success of the modification and the distribution of PNIPAM across the sample cross-sections. The results show that PNIPAM is mainly located in wood cell wall areas close to the lumen in early- and transitionwood.