Protein Corona Sensor Array Nanosystem for Detection of Coronary Artery Disease.

Coronary artery disease (CAD) is the most common type of heart disease and represents the leading cause of death in both men and women worldwide. Early detection of CAD is crucial for decreasing mortality, prolonging survival, and improving patient quality of life. Herein, a non-invasive is described, nanoparticle-based diagnostic technology which takes advantages of proteomic changes in the nano-bio interface for CAD detection. Nanoparticles (NPs) exposed to biological fluids adsorb on their surface a layer of proteins, the "protein corona" (PC). Pathological changes that alter the plasma proteome can directly result in changes in the PC. By forming disease-specific PCs on six NPs with varying physicochemical properties, a PC-based sensor array is developed for detection of CAD using specific PC pattern recognition. While the PC of a single NP may not provide the required specificity, it is reasoned that multivariate PCs across NPs with different surface chemistries, can provide the desirable information to selectively discriminate the condition under investigation. The results suggest that such an approach can detect CAD with an accuracy of 92.84%, a sensitivity of 87.5%, and a specificity of 82.5%. These new findings demonstrate the potential of PC-based sensor array detection systems for clinical use.

Metal-Organic Framework as a New Type of Magnetothermally-Triggered On-Demand Release Carrier.

The development of external stimuli-controlled payload systems has been sought after with increasing interest toward magnetothermally-triggered drug release (MTDR) carriers due to their non-invasive features. However, current MTDR carriers present several limitations, such as poor heating efficiency caused by the aggregation of iron oxide nanoparticles (IONPs) or the presence of antiferromagnetic phases which affect their efficiency. Herein, a novel MTDR carrier is developed using a controlled encapsulation method that fully fixes and confines IONPs of various sizes within the metal-organic frameworks (MOFs). This novel carrier preserves the MOF's morphology, porosity, and IONP segregation, while enhances heating efficiency through the oxidation of antiferromagnetic phases in IONPs during encapsulation. It also features a magnetothermally-responsive nanobrush that is stimulated by an alternating magnetic field to enable on-demand drug release. The novel carrier shows improved heating, which has potential applications as contrast agents and for combined chemo and magnetic hyperthermia therapy. It holds a great promise for magneto-thermally modulated drug dosing at tumor sites, making it an exciting avenue for cancer treatment.

Nonoperative and Operative Soft-Tissue, Cartilage, and Bony Regeneration and Orthopaedic Biologics of the Elbow and Upper Extremity: An Orthoregeneration Network Foundation Review.

Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and, optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electromagnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the elbow and upper extremity, including the tendons (lateral epicondylitis, medial epicondylitis, biceps tendonitis, triceps tendonitis), articular cartilage (osteoarthritis, osteochondral lesions), and bone (fractures, nonunions, avascular necrosis, osteonecrosis). Promising and established treatment modalities include hyaluronic acid; botulinum toxin; corticosteroids; leukocyte-rich and leukocyte-poor platelet-rich plasma; autologous blood; bone marrow aspirate comprising mesenchymal stromal cells (alternatively termed medicinal signaling cells and frequently mesenchymal stem cells [MSCs]) and bone marrow aspirate concentrate; MSCs harvested from adipose and skin (dermis) sources; vascularized bone grafts; bone morphogenic protein scaffold made from osteoinductive and conductive ß-tricalcium phosphate and poly-ε-caprolactone with hydrogels, human MSCs, and matrix metalloproteinases; and collagen sponge. Autologous blood preparations such as autologous blood injections and platelet-rich plasma show positive outcomes for nonresponsive tendinopathy. In addition, cellular therapies such as tissue-derived tenocyte-like cells and MSCs show a promising ability to regulate degenerative processes by modulating tissue response to inflammation and preventing continuous degradation and support tissue restoration.

Intraosseous Versus Intravenous Vancomycin in Tourniquetless Primary Total Knee Arthroplasty: A Randomized Trial.

BACKGROUND: Intraosseous (IO) administration of vancomycin at the time of total knee arthroplasty (TKA) has been shown to be safer and more effective than intravenous (IV) administration at preventing early periprosthetic joint infection. Previous studies have relied on tourniquet inflation to enhance local tissue concentrations and mitigate systemic release. METHODS: A single-blinded, randomized clinical trial was performed on 20 patients (10 IV, 10 IO) undergoing primary TKA. The control (IV) group received weight-dosed vancomycin approximately 1 hour prior to the incision and weight-dosed cefazolin immediately prior to the incision. The interventional (IO) group received weight-dosed cefazolin immediately prior to the incision and 500 mg of vancomycin delivered via the IO technique at the time of the incision. Systemic samples for vancomycin levels were taken prior to the incision and at closure. During the procedure, tissue samples were taken from the distal femur, proximal tibia, and suprapatellar synovium. There were no differences in patient demographics or changes in serum creatinine from preoperative to postoperatively between groups. RESULTS: Significant differences in systemic vancomycin levels (ug/mL) were found at the start of the case (IV = 27.9 ± 4.9 versus IO = 0 ± 0, P = .0004) and at the end of the case (IV = 19.6 ± 2.6 versus IO = 7.8 ± 1.0, P = .001). No significant differences were seen in the average vancomycin concentration in the distal femur (IV = 61.0 ± 16.0 versus IO = 66.2 ± 12.3, P = .80), proximal tibia (IV = 52.8 ± 13.5 versus IO = 57.1 ± 17.0, P = .84), or suprapatellar synovial tissue (IV = 10.7 ± 5.3 versus IO = 9.0 ± 3.3, P = .80). There were no complications associated with vancomycin administration in either group. CONCLUSIONS: This study demonstrates the utility of IO vancomycin in tourniquetless TKA with similar local tissue and significantly lower systemic concentrations than IV administration. LEVEL OF EVIDENCE: Level 1 therapeutic randomized trial.

Mice deficient for G-protein-coupled receptor 75 display altered presynaptic structural protein expression and disrupted fear conditioning recall.

There are a number of G-protein-coupled receptors (GPCRs) that are considered "orphan receptors" because the information on their known ligands is incomplete. Yet, these receptors are important targets to characterize, as the discovery of their ligands may lead to potential new therapies. GPR75 was recently deorphanized because at least two ligands appear to bind to it, the chemokine CCL5 and the eicosanoid 20-Hydroxyeicosatetraenoic acid. Recent reports suggest that GPR75 may play a role in regulating insulin secretion and obesity. However, little is known about the function of this receptor in the brain. To study the function of GPR75, we have generated a knockout (KO) mouse model of this receptor and we evaluated the role that this receptor plays in the adult hippocampus by an array of histological, proteomic, and behavioral endpoints. Using RNAscope® technology, we identified GPR75 puncta in several Rbfox3-/NeuN-positive cells in the hippocampus, suggesting that this receptor has a neuronal expression. Proteomic analysis of the hippocampus in 3-month-old GPR75 KO animals revealed that several markers of synapses, including synapsin I and II are downregulated compared with wild type (WT). To examine the functional consequence of this down-regulation, WT and GPR75 KO mice were tested on a hippocampal-dependent behavioral task. Both contextual memory and anxiety-like behaviors were significantly altered in GPR75 KO, suggesting that GPR75 plays a role in hippocampal activity.

Otto Aufranc Award: Intraosseous Vancomycin in Total Hip Arthroplasty - Superior Tissue Concentrations and Improved Efficiency.

BACKGROUND: Literature shows that intraosseous (IO) infusions are capable of providing increased local concentrations compared to those administered via intravenous (IV) access. Successes while using the technique for antibiotic prophylaxis administration in total knee arthroplasty (TKA) prompted consideration for use in total hip arthroplasty (THA) however; no study exists for the use of IO vancomycin in THA. METHODS: This single-blinded randomized control trial was performed from December 2020 to May 2022. Twenty patients were randomized into 1 of 2 groups: IV vancomycin (15 mg/kg) given routinely, or IO vancomycin (500 mg/100cc of NS) injected into the greater trochanter during incision. Serum vancomycin levels were collected at incision and closure. Soft tissue vancomycin levels were taken from the gluteus maximus (at start and end of case), and acetabular pulvinar tissue. Bone vancomycin levels were taken from the femoral head, acetabular reamings, and intramedullary bone. Adverse local/systemic reactions, 30-day complications, and 90-day complications were also tracked. RESULTS: A statistically significant reduction in serum vancomycin levels was seen when comparing IO to IV vancomycin at both the start and at the end of the procedure. All local tissue samples had higher concentrations of vancomycin in the IO group. Statistically significant increases were present within the acetabular bone reamings, and approached significance in intramedullary femoral bone. CONCLUSION: This study demonstrates the utility of IO vancomycin in primary THA with increased local tissue and decreased systemic concentrations. With positive findings in an area without tourniquet use, IO may be considered for antibiotic delivery for alternative procedures.

Reasons for the Sex Bias in Osteoarthritis Research: A Review of Preclinical Studies.

Osteoarthritis (OA) is one of the most common degenerative diseases of articular cartilage. During OA, all the elements that contribute to the joint undergo physiological and structural changes that impair the joint function and cause joint pain and stiffness. OA can arise naturally, with the aging population witnessing an increase in diagnoses of this pathology, but the root causes of OA have yet to be identified, and increasing interest is arising towards investigating biological sex as a risk factor. Clinical studies show increased prevalence and worse clinical outcomes for female patients, yet most clinical and preclinical studies have disproportionately focused on male subjects. This review provides a critical overview of preclinical practices in the context of OA, highlighting the underlying need for taking biological sex as both a risk factor and an important component affecting treatment outcome. A unique insight into the possible reasons for female underrepresentation in preclinical studies is offered, including factors such as lack of specific guidelines requiring the analysis of sex as a biological variable (SABV), research-associated costs and animal handling, and wrongful application of the reduction principle. Additionally, a thorough investigation of sex-related variables is provided, stressing how each of them could add valuable information for the understanding of OA pathophysiology, as well as sex-dependent treatment strategies.

Electrospun electroconductive constructs of aligned fibers for cardiac tissue engineering.

Myocardial infarction remains the leading cause of death in the western world. Since the heart has limited regenerative capabilities, several cardiac tissue engineering (CTE) strategies have been proposed to repair the damaged myocardium. A novel electrospun construct with aligned and electroconductive fibers combining gelatin, poly(lactic-co-glycolic) acid and polypyrrole that may serve as a cardiac patch is presented. Constructs were characterized for fiber alignment, surface wettability, shrinkage and swelling behavior, porosity, degradation rate, mechanical properties, and electrical properties. Cell-biomaterial interactions were studied using three different types of cells, Neonatal Rat Ventricular Myocytes (NRVM), human lung fibroblasts (MRC-5) and induced pluripotent stem cells (iPSCs). All cell types showed good viability and unique organization on construct surfaces depending on their phenotype. Finally, we assessed the maturation status of NRVMs after 14 days by confocal images and qRT-PCR. Overall evidence supports a proof-of-concept that this novel biomaterial construct could be a good candidate patch for CTE applications.

Intraosseous Morphine Decreases Postoperative Pain and Pain Medication Use in Total Knee Arthroplasty: A Double-Blind, Randomized Controlled Trial.

BACKGROUND: Intraosseous (IO) infusion of medication is a novel technique for total knee arthroplasty (TKA) antibiotic prophylaxis. To decrease postoperative pain in TKA patients, we investigated addition of morphine to a standard IO antibiotic injection. METHODS: A double-blind, randomized controlled trial was performed on 48 (24 each) consecutive patients undergoing primary TKA. The control group received an IO injection of antibiotics as per the standard protocol. The experimental group received an IO antibiotic injection with 10 mg of morphine. Pain, nausea, and opioid use were assessed up to 14 days postoperatively. Morphine and interleukin-6 serum levels were obtained 10 hours postoperatively in a subgroup of 20 patients. RESULTS: The experimental group had lower Visual Analog Scale pain score at 1, 2, 3, and 5 hours postoperatively (P = .0032, P = .005, P = .020, P = .010). This trend continued for postoperative day 1, 2, 8, and 9 (40% reduction, P = .001; 49% reduction, P = .036; 38% reduction, P = .025; 33% reduction, P = .041). The experimental group had lower opioid consumption than the control group for the first 48 hours and second week postsurgery (P < .05). Knee Injury and Osteoarthritis Outcome Score for Joint Replacement scores for the experimental group showed significant improvement at 2 and 8 weeks postsurgery (P < .05). Serum morphine levels in the experimental group were significantly less than the control group 10 hours after IO injection (P = .049). CONCLUSION: IO morphine combined with a standard antibiotic solution demonstrates superior postoperative pain relief immediately and up to 2 weeks. IO morphine is a safe and effective method to lessen postoperative pain in TKA patients. LEVEL OF EVIDENCE: Therapeutic, Level 1.

Biomimetic Nanoparticles as a Theranostic Tool for Traumatic Brain Injury.

Traumatic brain injury (TBI) triggers both central and peripheral inflammatory responses. Existing pharmacological drugs are unable to effectively and quickly target the brain inflamed regions, setting up a major roadblock towards effective brain trauma treatments. Nanoparticles (NPs) have been used in multiple diseases as drug delivery tools with remarkable success due to their rapid diffusion and specificity in the target organ. Here, leukocyte-based biomimetic NPs are fabricated as a theranostic tool to directly access inflamed regions in a TBI mouse model. This NP systemic delivery is visualized using advanced in vivo imaging techniques, including intravital microscopy and in vivo imaging system. The results demonstrate selective targeting of NPs to the injured brain and increased NPs accumulation among the peripheral organs 24 h after TBI. Interestingly, increased microglial proliferation, decreased macrophage infiltration, and reduced brain lesion following the NPs treatments compared to sham vehicle-treated mice are also found. In summary, the results suggest that NPs represent a promising future theranostic tool for TBI treatment.

Mimicking cardiac tissue complexity through physical cues: A review on cardiac tissue engineering approaches.

Cardiovascular diseases are the number one killer in the world.1,2 Currently, there are no clinical treatments to regenerate damaged cardiac tissue, leaving patients to develop further life-threatening cardiac complications. Cardiac tissue has multiple functional demands including vascularization, contraction, and conduction that require many synergic components to properly work. Most of these functions are a direct result of the cardiac tissue structure and composition, and, for this reason, tissue engineering strongly proposed to develop substitute engineered heart tissues (EHTs). EHTs usually have combined pluripotent stem cells and supporting scaffolds with the final aim to repair or replace the damaged native tissue. However, as simple as this idea is, indeed, it resulted, after many attempts in the field, to be very challenging. Without design complexity, EHTs remain unable to mature fully and integrate into surrounding heart tissue resulting in minimal in vivo effects.3 Lately, there has been a growing body of evidence that a complex, multifunctional approach through implementing scaffold designs, cellularization, and molecular release appears to be essential in the development of a functional cardiac EHTs.4-6 This review covers the advancements in EHTs developments focusing on how to integrate contraction, conduction, and vascularization mimics and how combinations have resulted in improved designs thus warranting further investigation to develop a clinically applicable treatment.

Mechanical Studies of the Third Dimension in Cancer: From 2D to 3D Model.

From the development of self-aggregating, scaffold-free multicellular spheroids to the inclusion of scaffold systems, 3D models have progressively increased in complexity to better mimic native tissues. The inclusion of a third dimension in cancer models allows researchers to zoom out from a significant but limited cancer cell research approach to a wider investigation of the tumor microenvironment. This model can include multiple cell types and many elements from the extracellular matrix (ECM), which provides mechanical support for the tissue, mediates cell-microenvironment interactions, and plays a key role in cancer cell invasion. Both biochemical and biophysical signals from the extracellular space strongly influence cell fate, the epigenetic landscape, and gene expression. Specifically, a detailed mechanistic understanding of tumor cell-ECM interactions, especially during cancer invasion, is lacking. In this review, we focus on the latest achievements in the study of ECM biomechanics and mechanosensing in cancer on 3D scaffold-based and scaffold-free models, focusing on each platform's level of complexity, up-to-date mechanical tests performed, limitations, and potential for further improvements.

MicroRNAs Modulate Signaling Pathways in Osteogenic Differentiation of Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) have been identified in many adult tissues and they have been closely studied in recent years, especially in view of their potential use for treating diseases and damaged tissues and organs. MSCs are capable of self-replication and differentiation into osteoblasts and are considered an important source of cells in tissue engineering for bone regeneration. Several epigenetic factors are believed to play a role in the osteogenic differentiation of MSCs, including microRNAs (miRNAs). MiRNAs are small, single-stranded, non-coding RNAs of approximately 22 nucleotides that are able to regulate cell proliferation, differentiation and apoptosis by binding the 3' untranslated region (3'-UTR) of target mRNAs, which can be subsequently degraded or translationally silenced. MiRNAs control gene expression in osteogenic differentiation by regulating two crucial signaling cascades in osteogenesis: the transforming growth factor-beta (TGF-ß)/bone morphogenic protein (BMP) and the Wingless/Int-1(Wnt)/ß-catenin signaling pathways. This review provides an overview of the miRNAs involved in osteogenic differentiation and how these miRNAs could regulate the expression of target genes.

Endosomal Escape of Polymer-Coated Silica Nanoparticles in Endothelial Cells.

Current investigations into hazardous nanoparticles (i.e., nanotoxicology) aim to understand the working mechanisms that drive toxicity. This understanding has been used to predict the biological impact of the nanocarriers as a function of their synthesis, material composition, and physicochemical characteristics. It is particularly critical to characterize the events that immediately follow cell stress resulting from nanoparticle internalization. While reactive oxygen species and activation of autophagy are universally recognized as mechanisms of nanotoxicity, the progression of these phenomena during cell recovery has yet to be comprehensively evaluated. Herein, primary human endothelial cells are exposed to controlled concentrations of polymer-functionalized silica nanoparticles to induce lysosomal damage and achieve cytosolic delivery. In this model, the recovery of cell functions lost following endosomal escape is primarily represented by changes in cell distribution and the subsequent partitioning of particles into dividing cells. Furthermore, multilamellar bodies are found to accumulate around the particles, demonstrating progressive endosomal escape. This work provides a set of biological parameters that can be used to assess cell stress related to nanoparticle exposure and the subsequent recovery of cell processes as a function of endosomal escape.

The viral protein gp120 decreases the acetylation of neuronal tubulin: potential mechanism of neurotoxicity.

The human immunodeficiency virus (HIV) envelope protein gp120 promotes axonal damage and neurite pruning, similar to that observed in HIV-positive subjects with neurocognitive disorders. Thus, gp120 has been used to examine molecular and cellular pathways underlying HIV-mediated neuronal dysfunction. Gp120 binds to tubulin beta III, a component of neuronal microtubules. Microtubule function, which modulates the homeostasis of neurons, is regulated by polymerization and post-translational modifications. Based on these considerations, we tested the hypothesis that gp120 induces dynamic instability of neuronal microtubules. We first observed that gp120 prevents the normal polymerization of tubulin in vitro. We then tested whether gp120 alters the post-translational modifications in tubulin by examining the ability of gp120 to change the levels of acetylated tubulin in primary rat neuronal cultures. Gp120 elicited a time-dependent decrease in tubulin acetylation that was reversed by Helix-A peptide, a compound that competitively displaces the binding of gp120 to neuronal microtubules. To determine whether post-translational modifications in tubulin also occur in vivo, we measured acetylated tubulin in the cerebral cortex of HIV transgenic rats (HIV-tg). We observed a decrease in tubulin acetylation in 5- and 9-month-old HIV-tg rats when compared to age-matched wild type. Neither changes in microglia morphology nor alterations in mRNA levels for interleukin-1ß and tumor necrosis factor α were detected in 5-month-old animals. Our findings propose neuronal microtubule instability as a novel mechanism of HIV neurotoxicity, without evidence of enhanced inflammation.

Identification of a binding site of the human immunodeficiency virus envelope protein gp120 to neuronal-specific tubulin.

Human immunodeficiency virus-1 (HIV) promotes synaptic simplification and neuronal apoptosis, and causes neurological impairments termed HIV-associated neurological disorders. HIV-associated neurotoxicity may be brought about by acute and chronic mechanisms that still remain to be fully characterized. The HIV envelope glycoprotein gp120 causes neuronal degeneration similar to that observed in HIV-associated neurocognitive disorders subjects. This study was undertaken to discover novel mechanisms of gp120 neurotoxicity that could explain how the envelope protein promotes neurite pruning. Gp120 has been shown to associate with various intracellular organelles as well as microtubules in neurons. We then analyzed lysates of neurons exposed to gp120 with liquid chromatography mass spectrometry for potential protein interactors. We found that one of the proteins interacting with gp120 is tubulin ß-3 (TUBB3), a major component of neuronal microtubules. We then tested the hypothesis that gp120 binds to neuronal microtubules. Using surface plasmon resonance, we confirmed that gp120 binds with high affinity to neuronal-specific TUBB3. We have also identified the binding site of gp120 to TUBB3. We then designed a small peptide (Helix-A) that displaced gp120 from binding to TUBB3. To determine whether this peptide could prevent gp120-mediated neurotoxicity, we cross-linked Helix-A to mesoporous silica nanoparticles (Helix-A nano) to enhance the intracellular delivery of the peptide. We then tested the neuroprotective property of Helix-A nano against three strains of gp120 in rat cortical neurons. Helix-A nano prevented gp120-mediated neurite simplification as well as neuronal loss. These data propose that gp120 binding to TUBB3 could be another mechanism of gp120 neurotoxicity. We propose a novel direct mechanism of human immunodeficiency virus neurotoxicity. Our data show that the viral protein gp120 binds to neuronal specific tubulin ß-3 and blocks microtubule transport. Displacing gp120 from binding to tubulin by a small peptide prevents gp120-mediated neuronal loss. Our study reveals a novel target for developing adjunct therapies against viral infection that promotes neurocognitive disorders.

Nanocomposite Hydrogels as Platform for Cells Growth, Proliferation, and Chemotaxis.

The challenge of mimicking the extracellular matrix with artificial scaffolds that are able to reduce immunoresponse is still unmet. Recent findings have shown that mesenchymal stem cells (MSC) infiltrating into the implanted scaffold have effects on the implant integration by improving the healing process. Toward this aim, a novel polyamidoamine-based nanocomposite hydrogel is synthesized, cross-linked with porous nanomaterials (i.e., mesoporous silica nanoparticles), able to release chemokine proteins. A comprehensive viscoelasticity study confirms that the hydrogel provides optimal structural support for MSC infiltration and proliferation. The efficiency of this hydrogel, containing the chemoattractant stromal cell-derived factor 1α (SDF-1α), in promoting MSC migration in vitro is demonstrated. Finally, subcutaneous implantation of SDF-1α-releasing hydrogels in mice results in a modulation of the inflammatory reaction. Overall, the proposed SDF-1α-nanocomposite hydrogel proves to have potential for applications in tissue engineering.

Biomimetic Concealing of PLGA Microspheres in a 3D Scaffold to Prevent Macrophage Uptake.

Scaffolds functionalized with delivery systems for the release of growth factors is a robust strategy to enhance tissue regeneration. However, after implantation, macrophages infiltrate the scaffold, eventually initiating the degradation and clearance of the delivery systems. Herein, it is hypothesized that fully embedding the poly(d,l-lactide-co-glycolide acid) microspheres (MS) in a highly structured collagen-based scaffold (concealing) can prevent their detection, preserving the integrity of the payload. Confocal laser microscopy reveals that non-embedded MS are easily internalized; when concealed, J774 and bone marrow-derived macrophages (BMDM) cannot detect them. This is further demonstrated by flow cytometry, as a tenfold decrease is found in the number of MS engulfed by the cells, suggesting that collagen can cloak the MS. This correlates with the amount of nitric oxide and tumor necrosis factor-α produced by J774 and BMDM in response to the concealed MS, comparable to that found for non-functionalized collagen scaffolds. Finally, the release kinetics of a reporter protein is preserved in the presence of macrophages, only when MS are concealed. The data provide detailed strategies for fabricating three dimensional (3D) biomimetic scaffolds able to conceal delivery systems and preserve the therapeutic molecules for release.

Thiol-ene mediated neoglycosylation of collagen patches: a preliminary study.

Despite the relevance of carbohydrates as cues in eliciting specific biological responses, the covalent surface modification of collagen-based matrices with small carbohydrate epitopes has been scarcely investigated. We report thereby the development of an efficient procedure for the chemoselective neoglycosylation of collagen matrices (patches) via a thiol-ene approach, between alkene-derived monosaccharides and the thiol-functionalized material surface. Synchrotron radiation-induced X-ray photoelectron spectroscopy (SR-XPS), Fourier transform-infrared (FT-IR), and enzyme-linked lectin assay (ELLA) confirmed the effectiveness of the collagen neoglycosylation. Preliminary biological evaluation in osteoarthritic models is reported. The proposed methodology can be extended to any thiolated surface for the development of smart biomaterials for innovative approaches in regenerative medicine.