Acid Scaffolds Research Articles

Investigation and multiscale modeling of PVA/SA coated poly lactic acid scaffold containing curcumin loaded layered double hydroxide nanohybrids.

Applying hydrophilic coatings on polymeric nanofibers combined with layered double hydroxide (LDH) not only enhances the efficiency of drug delivery systems but also increases cell adhesion. This work aimed to prepare poly(vinyl alcohol)/sodium alginate (PVA/SA) (2/1)-coated poly(lactic acid) (PLA) nanofibers containing curcumin-loaded layered double hydroxide (LDH) and to investigate their drug release and mechanical properties and their biocompatibility. The optimum PLA nanofibrous sample was considered to be that based on 3 wt% of curcumin-loaded LDH (PLA-3%LDH) with a drug encapsulation efficiency of ∼18% in which a minimum average nanofiber diameter of ∼476 nm along with a high tensile strength of 3.00 MPa were obtained. In the next step, a PVA/SA (2/1) layer was coated on the PLA-3%LDH; as a result, the hydrophilicity of the sample was improved and the elongation at break was decreased remarkably. In this regard the cell viability reached 80% for the coated PLA. Moreover, the formation of a layer of (PVA/SA) on the PLA nanofibers lowered the burst release and resulted in a more sustained drug release, which is a vital feature in dermal applications. A multiscale modeling method was applied for simulation of the mechanical properties of the composite scaffold and the results showed that this method can predict the data with 83% accuracy. The results of this study indicate that the formation of a layer of PVA/SA (2/1) has a significant effect on hydrophilicity and consequently improves cell adhesion and proliferation.

Highly sensitive and rapid detection of hypochlorous acid in aqueous media and its bioimaging in live cells and zebrafish using an ESIPT-driven mycophenolic acid-based fluorescent probe.

Excessive production of potent biological oxidants such as HOCl has been implicated in numerous diseases. Thus, it is crucial to develop highly specific and precise methods to detect HOCl in living systems, preferably with molecules that can show a distinct therapeutic effect. Our study introduces the synthesis and application of a highly sensitive fluorescence "turn-on" probe, Myco-OCl, based on the mycophenolic acid scaffold with exceptional water solubility. The ESIPT-driven mechanism enables Myco-OCl to specifically and rapidly detect (<5 s) HOCl with an impressive Stokes shift of 105 nm (λex = 417 nm, λem = 522 nm) and a sub-nanomolar (97.3 nM) detection limit with the detection range of 0 to 50 μM. The potential of Myco-OCl as an excellent biosensor is evident from its successful application for live cell imaging of exogenous and endogenous HOCl. In addition, Myco-OCl enabled us to detect HOCl in a zebrafish inflammatory animal model. These underscore the great potential of Myco-OCl for detecting HOCl in diverse physiological systems. Our findings thus offer a highly promising tool for detecting HOCl in living organisms.

Discovery of N-sulfonylated aminosalicylic acids as dual MCL-1/BCL-xL inhibitors.

The anti-apoptotic protein MCL-1, which is overexpressed in multiple cancers, is presently a focus for the development of targeted drugs in oncology. We previously discovered inhibitors of MCL-1 based on 1-sulfonylated 1,2,3,4-tetrahydroquinoline-6-carboxylic acids ("1,6-THQs"). However, with the nitrogen atom constrained in the bicyclic ring, we were unable to modify the alkyl portion of the tertiary sulfonamide functionality. Moreover, the introduction of additional functional groups onto the benzene ring portion of the THQ bicycle would not be trivial. Therefore, we elected to deconstruct the piperidine-type ring of the 6-carboxy-THQ lead to create a new 4-aminobenzoic acid scaffold. Given its simplicity, this permitted us to introduce diversity at the sulfonamide nitrogen, as well as vary the positions and substituents of the benzene ring. One of our most potent MCL-1 inhibitors, 6e-OH, exhibited a K i of 0.778 μM. Heteronuclear single quantum coherence experiments suggested 6e-OH bound in the canonical BH3-binding groove, with significant perturbations of R263, which forms a salt bridge with MCL-1's pro-apoptotic binding partners, as well as residues in the p2 pocket. Selectivity studies indicated that our compounds are dual inhibitors of MCL-1 and BCL-xL, with 17cd the most potent dual inhibitor: K i = 0.629 μM (MCL-1), 1.67 μM (BCL-xL). Whilst selective inhibitors may be more desirable in certain instances, polypharmacological agents whose additional target(s) address other pathways associated with the disease state, or serve to counter resistance mechanisms to the primary target, may prove particularly effective therapeutics. Since selective MCL-1 inhibition may be thwarted by overexpression of sister anti-apoptotic proteins, including BCL-xL and BCL-2, we believe our work lays a solid foundation towards the development of multi-targeting anti-cancer drugs.

Delivery of rivaroxaban and chitosan rapamycin microparticle with dual antithrombosis and antiproliferation functions inhibits venous neointimal hyperplasia

Neointimal hyperplasia is a complex process after vascular interventions, acute platelet deposition and smooth muscle cell proliferation both contributed to this process. There are still no perfect solutions to solve this problem. Rivaroxaban is a novel anticoagulant that has been widely used in clinic, it has a good pharmacological effects both in vivo and in vitro. Chitosan microparticle rapamycin (MP-rapa) was fabricated, interspaces of polyglycolic acid (PGA) scaffold were used as a reservoir of MP-rapa, and the scaffold was coated with hyaluronic acid rivaroxaban (MP-rapa-riva). Scanning electronic microscopy (SEM) photographs were taken and water contact angles were measured, rat inferior vena cava (IVC) patch venoplasty model was used; patches were harvested at day 14 and examined by immunohistochemistry and immunofluorescence. SEM photographs showed the microparticles rapamycin were inside the interspace of the scaffold, hyaluronic acid rivaroxaban was also successfully coated onto the surface of the scaffold. There was a thinner neointima, fewer proliferating cell nuclear antigen (PCNA) positive cells, fewer macrophages in the MP-rapa and MP-rapa-riva grafts compared to the control PGA graft. The result showed that this scaffold with dual anticoagulation and antiproliferation functions can effectively inhibit venous neointimal hyperplasia, although this is an animal experiment, it showed promising potential clinical application in the future.

Strontium-doped mesoporous bioactive glass microspheres developed for drug delivering and enhancing the bioactivity of polylactic acid scaffolds

Strontium-doped mesoporous bioactive glass microspheres (Sr-MBGMs) were prepared by sol–gel method for delivering loxoprofen sodium (LX) drug. The loading capacity of the prepared Sr-MBGMs for LX drug was affected by the initial concentration of the drug solution and adsorption time. The LX-loaded Sr-MBGMs obtained under optimum conditions were coated with polydopamine (LX/Sr-MBGMs@PDA) and incorporated into the aminated modified poly-l-lactic acid nanofibrous matrix to develop a functional composite scaffold for bone tissue engineering applications. The in vitro studies revealed that the incorporation of the LX/Sr-MBGMs@PDA could promote cell proliferation and biomineralization, indicating that the as-developed composite scaffolds possessed an improved cell viability and osteogenic ability.

Nitric Oxide-Releasing Bioinspired Scaffold for Exquisite Regeneration of Osteoporotic Bone via Regulation of Homeostasis.

Osteoporotic bone regeneration is a challenging process which involves the occurrence of sophisticated interactions. Although various polymeric scaffolds have been proposed for bone repair, research on osteoporotic bone regeneration remains practically limited. In particular, achieving satisfactory bone regeneration when using osteoporotic drugs is challenging including bisphosphonates. Here, a novel nitric oxide-releasing bioinspired scaffold with bioactive agents for the exquisite regeneration of osteoporotic bone is proposed. The bone-like biomimetic poly(lactic-co-glycolic acid) scaffold is first prepared in combination with organic/inorganic ECM and magnesium hydroxide as the base implant material. Nanoparticles containing bioactive agents of zinc oxide (ZO), alendronate, and BMP2 are incorporated to the biomimetic scaffold to impart multifunctionality such as anti-inflammation, angiogenesis, anti-osteoclastogenesis, and bone regeneration. Especially, nitric oxide (NO) generated from ZO stimulates the activity of cGMP and protein kinase G; in addition, ZO downregulates the RANKL/osteoprotegerin ratio by suppressing the Wnt/β-catenin signaling pathway. The new bone is formed much better in the osteoporotic rat model than in the normal model through the regulation of bone homeostasis via the scaffold. These synergistic effects suggest that such a bioinspired scaffold could be a comprehensive way to regenerate exceptionally osteoporotic bones.

Biomimetic surface modification of Three-dimensional printed Polylactic acid scaffolds with custom mechanical properties for bone reconstruction.

3D printing has recently emerged as an innovative fabrication method to construct critical-sized and patient-specific bone scaffolds. The ability to control the bulk geometry of scaffolds in both macro and micro-scales distinguishes this technology from other fabrication methods. In this study, bone tissue-specific scaffolds with different pore geometries were printed from polylactic acid (PLA) filaments at three given infill densities ranging from 20 to 30%. A hybrid hydrogel made of synthetic biphasic calcium phosphate (BCP) and collagen was applied to coat 3D printed well-structured triangular samples with 30% infill density. The coating process changed the surface texture, increased the average strand diameter and average pore size, and decreased the open porosity of samples, all of which increased the mechanical strength of biomimetic-coated scaffolds. According to matrix mineralization staining and osteo-related gene expression, the coating of scaffolds significantly facilitates metabolic activity and osteogenic differentiation of dental pulp-derived mesenchymal stem cells (DPSCs). Taken together, these results indicated that the biomimetic coating is a highly promising approach that could be taken into consideration in the design of a porous scaffold for bone tissue engineering.

Insight into Stereocontrol in the Asymmetric Intramolecular Allylation with a tert-Butylsulfinamide Nucleophile: Application in the Synthesis of Chiral Isoindoline-1-Carboxylic Acid Esters.

The asymmetric induction afforded by a chiral sulfinyl group in a palladium/Brønsted-acid-catalyzed intramolecular allylic amination was investigated. Predictions of the diastereoselectivity for various substrates under assumed total thermodynamic control were obtained from density functional theory (DFT), and the correlation with experimental data demonstrates abrupt changes to kinetic control across the substrate scope. The resulting heterocyclic product was readily converted to valuable isoindoline-1-carboxylic acid esters by a two-step oxidation sequence, providing asymmetric access to a key unnatural α-amino acid scaffold.

Fabrication and assessment of bifunctional electrospun poly(l-lactic acid) scaffolds with bioglass and zinc oxide nanoparticles for bone tissue engineering

Electrospun scaffolds based on poly(l-lactic acid) (PLLA) with bioglass (n-BG) and zinc oxide (n-ZnO), and mixture of both, were developed to design bifunctional biomaterials with enhanced bioactive and biocidal properties. The presence of n-BG increased the fiber diameter of the pure PLA from 1.5 ± 0.3 μm to 3.0 ± 0.8 μm for 20 wt%. ZnO and the mixed nanoparticles did not significantly affect the morphology. The mechanical properties decreased with the presence of nanoparticles. Scaffolds based on PLA/n-BG promoted hydroxyapatite (HA) formation in simulated body fluid (SBF) that was inhibited with the presence of ZnO. Notably, mixed particles produced bioactivity although at longer times. The incorporation of n-ZnO produced a biocidal capacity against S. aureus in the polymeric scaffold, reaching a viability reduction of 60 % after 6 h of exposure. When both types of nanoparticles were combined, the bacterial viability reduction was 30 %. Pure PLA scaffolds and the composites with n-BG showed good ST-2 bone marrow-derived cell line viability, scaffolds with n-BG (pure or mixture) presented lower viability. Results validated the use of both n-BG and n-ZnO fillers for the development of novel bifunctional PLA-based scaffolds with both bioactive and biocidal properties for bone tissue engineering applications.

Poly(l-lactic acid) Scaffold Releasing an α4β1 Integrin Agonist Promotes Nonfibrotic Skin Wound Healing in Diabetic Mice.

Skin wound healing is a highly complex process that continues to represent a major medical problem, due to chronic nonhealing wounds in several classes of patients and to possible fibrotic complications, which compromise the function of the dermis. Integrins are transmembrane receptors that play key roles in this process and that offer a recognized druggable target. Our group recently synthesized GM18, a specific agonist for α4β1, an integrin that plays a role in skin immunity and in the migration of neutrophils, also regulating the differentiated state of fibroblasts. GM18 can be combined with poly(l-lactic acid) (PLLA) nanofibers to provide a controlled release of this agonist, resulting in a medication particularly suitable for skin wounds. In this study, we first optimized a GM18-PLLA nanofiber combination with a 7-day sustained release for use as skin wound medication. When tested in an experimental pressure ulcer in diabetic mice, a model for chronic nonhealing wounds, both soluble and GM18-PLLA formulations accelerated wound healing, as well as regulated extracellular matrix synthesis toward a nonfibrotic molecular signature. In vitro experiments using the adhesion test showed fibroblasts to be a principal GM18 cellular target, which we then used as an in vitro model to explore possible mechanisms of GM18 action. Our results suggest that the observed antifibrotic behavior of GM18 may exert a dual action on fibroblasts at the α4β1 binding site and that GM18 may prevent profibrotic EDA-fibronectin-α4β1 binding and activate outside-in signaling of the ERK1/2 pathways, a critical component of the wound healing process.

Deoxyribonucleic acid scaffold assisted structural engineering to tune the intrinsic to extrinsic capacitive behavior in spinel structured MnCo2O4.5 for high-performance asymmetric supercapacitor application

The spinel structured materials (e.g., MnCo2O4.5) are good aspirants for supercapacitor electrode application due to their outstanding pseudocapacitor performance. However, due to the collapsing of the crystal and morphological structures during electrochemical analysis, inferior cyclic stability and low energy density problems are inevitable when the materials are used as supercapacitor electrodes. Alteration of intrinsic (diffusion-controlled) to extrinsic (surface-controlled) capacitive behavior is the effective solution to overcome these issues. Herein, the intrinsic capacitor behavior of the MnCo2O4.5 material was altered into an extrinsic mechanism through the precipitation process with the aid of a deoxyribonucleic acid (DNA)-based structural engineering process. The MnCo2O4.5 coated on nickel foam current collector delivered the specific capacity of 649C g−1 at 1 A g−1 and retained 97 % of its initial capacity after 5000 cycles at 20 A g−1 in three-electrode configurations. Additionally, the MnCo2O4.5//Activated carbon asymmetric device showed a specific capacity of 93.8C g−1 at 1 A g−1 with energy and power densities of 33.4 Wh Kg−1 and 681 W Kg−1 at 1 A g−1, respectively. DNA-based structural engineering demonstrates the tuning of intrinsic to extrinsic capacitive behavior resulting in better supercapacitor properties in MnCo2O4.5 material.

Ensemble Modified Aptamer Based Pattern Recognition for Adaptive Target Identification.

The difficulty of the molecular design and chemical synthesis of artificial sensing receptors restricts their diagnostic and proteomic applications. Herein, we report a concept of "ensemble modified aptamers" (EMAmers) that exploits the collective recognition abilities of a small set of protein-like side-chain-modified nucleic acid ligands for discriminative identification of molecular or cellular targets. Different types and numbers of hydrophobic functional groups were incorporated at designated positions on nucleic acid scaffolds to mimic amino acid side chains. We successfully assayed 18 EMAmer probes with differential binding affinities to seven proteins. We constructed an EMAmer-based chemical nose sensor and demonstrated its application in blinded unknown protein identification, giving a 92.9% accuracy. Additionally, the sensor is generalizable to the detection of blinded unknown bacterial and cellular samples, which enabled identification accuracies of 96.3% and 94.8%, respectively. This sensing platform offers a discriminative means for adaptive target identification and holds great potential for diverse applications.

8-Aminoquinoline-containing squaric acid congeners as polarity and viscosity probes

Squaraine-type dyes are privileged motifs and scaffolds with valuable and tunable photophysical properties, and have found numerous applications in various areas of chemical and biological sciences. Yet, environment-sensing capabilities of squaraine dyes have not been widely explored. This study illustrates how selective incorporation of a readily available 8-aminoquinoline moiety onto squaric acid or squarate scaffolds fine-tunes environment-sensing capabilities of these dyes. The squaraine motif is required for achieving meaningful correlations between probe’s photophysical properties and media’s properties, whereas semi-squaraine and squaramide analogues exhibit inferior environment-sensing capabilities. The 1,3-bis(8-aminoquinolinyl)squaraine dye shows potential as a multiplexing environment-sensitive probe that could sense media’s polarity variations via absorption changes, and environmental viscosity via amplitude-weighted fluorescence lifetime changes.

Hypoxia-mimicking scaffolds with controlled release of DMOG and PTHrP to promote cartilage regeneration via the HIF-1α/YAP signaling pathway

Efficiently driving chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) while avoiding undesired hypertrophy remains a challenge in the field of cartilage tissue engineering. Here, we report the sequential combined application of dimethyloxalylglycine (DMOG) and parathyroid hormone-related protein (PTHrP) to facilitate chondrogenesis and prevent hypertrophy. To support their delivery, poly(lactic-co-glycolic acid) (PLGA) microspheres were fabricated using a double emulsion method. Subsequently, these microspheres were incorporated onto a poly(l-lactic acid) (PLLA) scaffold with a highly porous structure, high interconnectivity and collagen-like nanofiber architecture to construct a microsphere-based scaffold delivery system. These functional constructs demonstrated that the spatiotemporally controlled release of DMOG and PTHrP effectively mimicked the hypoxic microenvironment to promote chondrogenic differentiation with phenotypic stability in a 3D culture system, which had a certain correlation with the interaction between hypoxia-inducible Factor 1 alpha (HIF-1α) and yes-associated protein (YAP). Subcutaneous implantation in nude mice revealed that the constructs were able to maintain cartilage formation in vivo at 4 and 8 weeks. Overall, this study indicated that DMOG and PTHrP controlled-release PLGA microspheres incorporated with PLLA nanofibrous scaffolds provided an advantageous 3D hypoxic microenvironment for efficacious and clinically relevant cartilage regeneration and is a promising treatment for cartilage injury.

Synthesis of New β‐Amino Acid Scaffolds by Means of Ring‐Rearrangement Metathesis

AbstractThe synthesis of some novel functionalized azaheterocyclic β‐amino esters with multiple chiral centers via a stereocontrolled synthetic route has been carried out using some cyclooctene β‐amino acids as starting model compounds. The strategy of the method was planned to create some novel unsaturated N‐protected cyclic β‐amino esters that were subjected to ring‐opening metathesis (ROM) followed by selective ring‐closing metathesis (RCM). A number of experimental conditions were accomplished to investigate the activity of catalysts, yields, conversions, and substrate effect on ring‐rearrangement metathesis (RRM) transformation. Importantly, the procedure used in this synthetic process does not affect the configuration of the chiral centers; therefore, the stereochemistry of the starting cyclooctadiene β‐amino acids predetermined the structure of the new azaheterocyclic derivatives.

The Use of Aryl-Substituted Homophthalic Anhydrides in the Castagnoli–Cushman Reaction Provides Access to Novel Tetrahydroisoquinolone Carboxylic Acid Bearing an All-Carbon Quaternary Stereogenic Center

Novel aryl-substituted homophthalic acids were cyclodehydrated to the respective homophthalic anhydrides for use in the Castagnoli-Cushman reaction. With a range of imines, this reaction proceeded smoothly and delivered hitherto undescribed 4-aryl-substituted tetrahydroisoquinolonic acids with remarkable diastereoselectivity, good yields and no need for chromatographic purification. These findings significantly extend the range of cyclic anhydrides employable in the Castagnoli-Cushman reaction and signify access to a novel substitution pattern around the medicinally relevant tetrahydroisoquinolonic acid scaffold.

Nucleic acid-based scaffold systems and application in enzyme cascade catalysis.

Enzymes, as elements with catalytic functions, can be rationally designed and multiple assembled to form a composite catalytic system and achieve cascade catalytic functions. Enzyme cascade catalysis could produce various chemical products with high conversion rate in short time. With the development of DNA nanotechnology, assembling enzymes to different nucleic acid-based scaffolds in different spatial organizations could effectively improve the catalytic efficiency of enzymes. Herein, we review the construction and application of nucleic acid-based scaffold systems from the perspective of template assembly in three dimensions. The challenges and future outlooks in the development of enzyme cascades are also discussed. KEY POINTS: • The principles and construction of various nucleic acid scaffolds are summarized • The application of nucleic acid scaffolds in enzyme cascade catalysis is discussed.

Effects of accelerated weathering on properties of 3D-printed PLA scaffolds

This work aims to analyze the effects of accelerated weathering – under different environmental variables – on the properties of poly(lactic acid) (PLA) scaffolds fabricated by Fused Filament Fabrication (FFF). Two methodologies were followed: at 35 and 45 °C, under temperature control alone (ASTM F1980), and under controlled cycles of temperature, ultraviolet (UV) radiation, and humidity (ASTM G154). Weathered samples were characterized by color visual analysis, differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). For weathering tests at 35 °C, and simultaneous control of temperature, radiation, and humidity (T-R-H), the degradation seemed to predominantly affect amorphous parts of the PLA scaffolds. For weathering at 45 °C, the degradation was prevalent on amorphous parts for initial exposure and, subsequently, also affected crystalline parts of the polymer. The accelerated weathering tests produced changes in the FTIR spectra, indicating intensified chain scissions by photolysis and hydrolysis, with more pronounced effects for the T-R-H test, followed by the tests under 45 °C and 35 °C. Noticeable surface defects appeared only on PLA samples subjected to the T-R-H test (336 h exposure), as a result of the more severe degradation generated by the combined variables of this accelerated weathering. • Poly(lactic acid) (PLA) scaffolds manufactured by Fused Filament Fabrication (FFF) • Different accelerated weathering tests performed with the PLA scaffolds • Changes in properties, due to weathering, assessed and compared • Effects of weathering tests linked to PLA degradation mechanisms

Biomineralization of bone-like hydroxyapatite to upgrade the mechanical and osteoblastic performances of poly(lactic acid) scaffolds

Biomimetic mineralization of high-strength apatite structure essentially relies on mimicking the inorganic building blocks of naturally occurring bones. However, conventional routes still have substantial function gaps in providing precision control over the geometrical dimensions and crystalline morphology of biomineralized apatite. Herein, we conceived the concept of microwave-assisted biomineralization (MAB) to customize 1D hydroxyapatite nanowhiskers (HANWs) at graphene templates, rendering the formation of graphene-hydroxyapatite (Gr-HA) nanohybrids. The HANWs essentially resembled bone apatite in elemental composition (Ca/P = 1.74), diameter (~20 nm), crystallinity (63 %), and rodlike geometry (aspect ratio of ~6). The Gr-HA nanohybrids were uniformly incorporated into poly(lactic acid) (PLA) microfibers (~1 μm) by electrospinning, engendering fibrous membranes with a set of Gr-HA loadings (10, 20 and 30 wt%). Intimate interactions were generated between Gr-HA and PLA matrix, contributing to significant promotion of the mechanical properties for PLA composite membranes. For example, the yield strength and elastic modulus of the PLA composite membranes loaded with 30 wt% Gr-HA achieved 5.4 and 66.4 MPa, increasing nearly 182 % and over 94 % compared to those of pure PLA, respectively. Moreover, the bone-like HANWs endowed PLA membranes with excellent cytocompatibility and good bioactivity, as demonstrated by over 38 % increase in cell viability and rapid apatite formation in mineral solution. The impressive combination of mechanical properties and biological characteristics make the PLA/Gr-HA scaffolds promising for guided tissue/bone regeneration therapy.

Satisfactory clinical outcomes with autologous matrix-induced chondrogenesis in the treatment of grade IV chondral injuries of the knee

ObjectiveThe research aims to evaluate short- and medium-term outcomes of patients treated using autologous matrix-induced chondrogenesis (AMIC) with a hyaluronic acid scaffold (Hyalofast, Anika Therapeutics, MA, USA) in grade IV chondral lesions according to the Outerbridge classification in the knee. MethodsThis is a multicentre, non-randomized, retrospective study conducted between 2017 and 2022. To determine the clinical outcome of the patients, the follow-up was done with the subjective International Knee Documentation Committee (IKDC) score, pre-surgery, and with a follow-up at 12, 24, and 32 months. ResultsFifty patients (28 female) with a mean age of 45.9 ± 12.7 years were recruited. The mean size of the lesion was 3.5 cm2, and the injuries located in the patella (30%) and trochlear groove (24%) were the most frequent. The total IKDC clinical score significantly increased from baseline to the 32 months of follow-up with a mean difference of 36.4 (95% CI, 29.1–43.7, p < 0.001). Besides, there was a statistically significant improvement in all categories of the IKDC (symptoms, sports activities, function, and activity of daily living) compared between pre-surgery and 24 and 32 months of follow-up. The patients younger than 45 years presented better clinical outcomes than older ones with a difference between medians of 10.40 (95% CI, 1.10–11.50, p = 0.0247), and a negative correlation was found between the 32-month IKDC score and the age. In addition, no statistically significant difference was found when comparing the last results of the IKDC between patients with and without associated surgical procedures or between patients with single and several lesions, neither nor between men and women. The level of satisfaction with the procedure of all the patients, on a score of 1–10, was on average 8 ± 1.5. ConclusionResults of this study indicate that patients who underwent the AMIC procedure with hyaluronic acid scaffold for the treatment of grade IV chondral lesions in the knee presented satisfactory results throughout the follow-up. Level of evidenceLevel IV