Uncontrolled side reactions during lignin isolation lead to a loss of chemical functionalities. Functionalization steps are thus usually performed on isolated lignin to improve reactivity and/or miscibility toward other materials. Even with these additional steps, potential high-performance applications are generally substantially curtailed. Here, we use aldehyde-assisted fractionation with two aldehydes containing other functionalities to introduce multiple functionalities on the lignin in a controlled way and in a single step from lignocellulosic biomass. The quantity of the various functionalities is easily tuned, imparting to the lignin different reactivity and solubility properties. These bifunctional lignins are employed to fabricate novel covalently bonded lignin-gelatin-based hydrogels by simple mixing of reagents at room temperature without the addition of initiators for soft tissue engineering. These hydrogels show enhanced and controllable mechanical (up to 134% in storage modulus and +107% in tensile strength compared to gelatin alone), adhesive, temperature-resistant, and self-healing properties at 37 degrees C and pH 7.4 only when a bifunctional lignin is used. This work demonstrates the importance and potential of controlled multifunctionalization of lignin, opening the way for its use in high-performance materials.

BACKGROUND AND OBJECTIVE:While there is a reported correlation between shoulder condition and scapular morphology, the precise impact of typical anatomical variables remains a subject of ongoing debate. This study aimed to evaluate this causal association, by emphasizing the importance of scientific modeling before statistical analysis. METHODS:We examined the effect of scapular anatomy on shoulder condition, and conditioning on sex, age, height, and weight. We considered the two most common pathologies: primary osteoarthritis (OA) and cuff tear arthropathy (CTA). We combined the other pathologies into a single category (OTH) and included a control category (CTRL) of adult subjects without pathology. We represented acromion and glenoid morphology by acromion angle (AA), acromion posterior angle (APA), acromion tilt angle (ATA), glenoid inclination angle (GIA), and glenoid version angle (GVA). GVA was negative for posterior orientation. These variables were automatically calculated from CT scans of 396 subjects in the 4 shoulder condition groups by a deep learning model. We applied do-calculus to assess the identifiability of the causal associations and used a multinomial logistic regression Bayesian model to estimate them. To isolate the effect of each anatomical variable on each shoulder condition, we increased it from -2 to 2 z-score while constraining all other variables to their average value, and reported the effect on shoulder condition probability as percentage points (pp) for females and males. RESULTS:Increasing AA reduced the probability of OA by 44 pp for females and 17 pp for males while increasing the probability of CTA by 36 pp for females and 33 pp for males. Increasing APA raised the probability of OA by 15 pp for females and 4 pp for males and increased the probability of CTA by 12 pp for females and 4 pp for males. Increasing ATA increased the probability of OA by 15 pp for females but decreased it by 25 pp for males, while also raising the probability of CTA by 11 pp for females and 21 pp for males. Increasing GIA decreased the probability of OA by 55 pp for females and 23 pp for males while increasing the probability of CTA by 45 pp for females and 31 pp for males. GVA (more anterior), decreased the probability of OA by 33 pp for females and 63 pp for males. The effects of APA and ATA were less important compared to the other variables. Overall, morphological effects were more pronounced for females than for males, except for GVA's impact on OA. CONCLUSIONS:We developed a Bayesian causal model to answer interventional questions about the scapular anatomy's effect on shoulder condition. Our results, consistent with clinical knowledge, hold promise for aiding in early pathology detection and optimizing surgical planning within clinical settings.

Sports helmets provide incomplete protection against brain injuries. Here we aim to improve helmet liner efficiency by employing a novel approach that optimizes their properties. By exploiting a finite element model that simulates head impacts, we developed deep learning models that predict the peak rotational velocity and acceleration of a dummy head protected by various liner materials. The deep learning models exhibited a remarkable correlation coefficient of 0.99 within the testing dataset with mean absolute error of 0.8 rad.s−1 and 0.6 krad.s−2 respectively, highlighting their predictive ability. Deep learning-based material optimization demonstrated a significant reduction in the risk of brain injuries, ranging from −5% to −65%, for impact energies between 250 and 500 Joules. This result emphasizes the effectiveness of material design to mitigate sport-related brain injury risks. This research introduces promising avenues for optimizing helmet designs to enhance their protective capabilities. Varanges and colleagues present a deep learning-based approach to optimize helmet liner materials for brain injury prevention. This method highlights the potential of AI-driven material design tailored for specific applications.

Articular cartilage's limited regenerative capacity is compounded by the overlooked thermomechanical factors critical to its function. Recent studies emphasize the importance of cartilage self-heating, arising predominantly from energy dissipation under physiological loading, in maintaining an optimal environment for chondrocyte activity. This thermal dimension, integral to cartilage homeostasis, is absent in traditional tissue engineering approaches, which may explain their limited success. A deeper integration of thermomechanical cues into regenerative strategies could thus be pivotal for advancing articular cartilage repair. Incorporating thermomechanical cues into regenerative strategies offers a practical pathway to revolutionize cartilage repair and regeneration. By mimicking the physiological environment through dynamic thermal and mechanical stimulation within bioreactors, these approaches hold promise for advancing tissue engineering models and optimizing in vitro culture conditions tailored to the complexities of cartilage regeneration. This Mini-Review aims to highlight the need for a paradigm shift in cartilage regeneration, advocating for approaches that incorporate dynamic thermal and mechanical stimuli to enhance therapeutic outcomes.

Mouthguards are primarily designed to attenuate the oral impacts and decrease the risk of dental damage. For this reason, they are recommended or obligatory in certain sports. However, only well-designed customized mouthguards could provide efficient protection and comfort. The high cost and long lead time for fabricating customized mouthguards with specific structural and material properties restrict their usage. Emerging digitalbased additive manufacturing technologies could overcome these difficulties. Accordingly, we propose an innovative strategy to create functional and custom-made mouthguards with 3D-printed interlockable components. The developed modular device comprises removable components with targeted properties for maximum performance. The protectiveness of the developed mouthguards was evaluated by direct impact tests on a 3Dprinted dental model using an impetus setup in different loading conditions. The impact tests revealed that significantly higher dental protection is achievable with thinner 3D-printed mouthguards than conventional multi-layered mouthguards such as the Playsafe (R) Heavypro type. In particular, the impact-induced strain on the incisors is reduced by >90 % with the protection of the 3D-printed modular mouthguards and only around 40 % with conventional Playsafe (R) Heavypro type in a mild testing condition compared to the situation without a mouthguard. We showed that both the material and the geometrical properties of the components of the modular mouthguards determine the level of protection. Based on our modular strategy, the developed mouthguard is adaptable to different sports, necessitating different levels of protection by swapping the removable components. Moreover, the developed mouthguard is durable as the hard insert can be replaced after an eventual damaging impact. Thanks to the developed design strategy, the selection of materials is no longer limited to chemically bondable compositions, offering a new flexibility to fine-tune the employed materials in specific jaw regions. Simultaneous maximal dental protection and athletes' comfort can be obtained.

BACKGROUND:The effect of shoulder pathologies on glenoid bone mineral density (BMD) remains unclear and can be critical in surgical treatments. It is thus useful to predict this effect and understand how it is influenced by sex, age, and body mass index (BMI), in various glenoid locations. METHODS:We developed a causal model and used do-calculus to identify the minimal adjustment set of covariate variables and developed a varying-intercept varying-slope Bayesian model. We considered two common shoulder pathologies, primary osteoarthritis (OA) and cuff tear arthropathy (CTA), and compared them with normal shoulders (CTRL). Glenoid BMD was automatically measured on computed tomography scans of 93 OA, 53 CTA, and 133 CTRL subjects. RESULTS:OA and CTA subjects had higher BMD than CTRL in subchondral trabecular bone. This difference varied by sex, increased with age, and was stable with BMI. BMD was higher in OA than CTA, especially on the posterior side. CONCLUSION:This causal model estimates the causal effect of pathology BMD, which could be useful for surgery planning, outcome prediction, and understanding of the associated pathophysiology.

Knee cartilage has limited natural healing capacity, complicating the development of effective treatment plans. Current non-cell-based therapies (e.g., microfracture) result in poor repair cartilage mechanical properties, low durability, and suboptimal tissue integration. Advanced treatments, such as autologous chondrocyte implantation, face challenges including cell leakage and inhomogeneous distribution. Successful cell therapy relies on prolonged retention of therapeutic biologicals at the implantation site, yet the optimal integration of implanted material into the surrounding healthy tissue remains an unmet need. This study evaluated the effectiveness of a newly developed photo-curable adhesive hydrogel for cartilage repair, focusing on adhesion properties, integration performance, and ability to support tissue regeneration. The proposed hydrogel design exhibited significant adhesion strength, outperforming commercial adhesives such as fibrin-based glues. An in vivo goat model was used to evaluate the hydrogels’ adhesion properties and long-term integration into full-thickness cartilage defects over six months. Results showed that cell-free hydrogel-treated defects achieved superior integration with surrounding tissue and enhanced cartilage repair, with notable lateral integration. In vitro results further demonstrated high cell viability, robust matrix production, and successful cell encapsulation within the hydrogel matrix. These findings highlight the potential of adhesive hydrogel formulations to improve the efficacy of cell-based therapies, offering a potentially superior treatment for knee cartilage defects.

INTRODUCTION:Managing osteoporotic patients at immediate fracture risk is challenging, in part due to the slow and localized effects of anti-osteoporotic drugs. Combining systemic anti-osteoporotic therapies with local bone augmentation techniques offers a promising strategy, but little is known about potential interactions. We hypothesized that integrating systemic treatments with local bone-strengthening biomaterials would have an additive effect on bone density and structure. This study investigated interactions and synergies between systemic therapies and injectable biomaterials, HA2 and HA2-ZOL, designed for local bone strengthening. HA2-ZOL incorporates Zoledronate, a bisphosphonate, to enhance anti-resorptive effects. These materials were tested in an in vivo rat model of osteoporosis using microCT and histology. METHODS:Thirty-six ovariectomized Wistar rats were treated systemically with vehicle (VEH), alendronate (ALN), or parathyroid hormone (PTH). One week later, their tibiae were randomly assigned to local treatment groups: HA2, HA2-ZOL, or NaCl control. Bilateral injections targeted metaphyseal trabecular bone, with microCT scans tracking changes over 8 weeks. Regions of interest (ROIs) were identified and analyzed for bone volume fraction (BV/TV), tissue mineral density (TMD), and trabecular morphology. Histological analyses were performed at week 8 to assess bone structure and mineral inclusions. RESULTS:VEH animals with NaCl injections experienced marked bone loss, partially mitigated by ALN and PTH. HA2 injections increased BV/TV by factors of 2.5 to 3.4 across treatments compared to baseline, with effects confined to the injected material. HA2-ZOL amplified this response, with BV/TV increases up to 4.8-fold, particularly in VEH and PTH animals. The effects peaked at 2-4 weeks post-injection, followed by remodeling and restoration. Both local treatments increased trabecular thickness, with HA2-ZOL showing slower post-peak resorption. DISCUSSION:HA2 injections significantly densified bone, independent of systemic therapy. Zoledronate in HA2-ZOL enhanced bone formation and delayed resorption in control and PTH animals, but offered no additional benefit when combined with systemic bisphosphonate. These findings support the hypothesis of an additive effect, suggesting that injectable hydrogels with localized drug delivery can complement systemic therapies by rapidly increasing local bone density, thereby potentially preventing fractures in high-risk osteoporotic patients.

Hyaline cartilage, a soft tissue enriched with a dynamic extracellular matrix, manifests as a supramolecular system within load-bearing joints. At the same time, the challenge of cartilage repair through tissue engineering lies in replicating intricate cellular-matrix interactions. This study attempts to investigate chondrocyte responses within double-network supramolecular hybrid hydrogels tailored to mimic the dynamic molecular nature of hyaline cartilage. To this end, we infused noncovalent host-guest polyrotaxanes, by blending α-cyclodextrins as host molecules and polyethylene glycol as guests, into a gelatin-based covalent matrix, thereby enhancing its dynamic characteristics. Subsequently, chondrocytes were seeded into these hydrogels to systematically probe the effects of two concentrations of the introduced polyrotaxanes (instilling different levels of supramolecular dynamism in the hydrogel systems) on the cellular responsiveness. Our findings unveiled an augmented level of cellular mechanosensitivity for supramolecular hydrogels compared to pure covalent-based systems. This is demonstrated by an increased mRNA expression of ion channels (TREK1, TRPV4, and PIEZO1), signaling molecules (SOX9) and matrix-remodeling enzymes (LOXL2). Such outcomes were further elevated upon external application of biomimetic thermomechanical loading, which brought a stark increase in the accumulation of sulfated glycosaminoglycans and collagen. Overall, we found that matrix adaptability plays a pivotal role in modulating chondrocyte responses within double-network supramolecular hydrogels. These findings hold the potential for advancing cartilage engineering within load-bearing joints.

Sports helmets do not provide full protection against brain injuries. Our study aims to improve helmet liner efficiency by employing a novel approach that optimizes their properties. By exploiting a finite element model that simulates impacts, we developed deep learning models that predict the peak kinematics of a dummy head protected by various liner materials. The models exhibited a remarkable correlation coefficient of 0.99 within the training dataset, highlighting their predictive ability. Deep learning-based material optimization predicts a significant reduction in the risk of traumatic axonal injuries for impact energy ranging from 250 to 450 Joules. This result emphasizes the effectiveness of a sophisticated material design to mitigate sport-related brain injury risks. This research introduces promising avenues for optimizing helmet designs to enhance their protective capabilities.

ObjectiveDuring physical activities, chondrocytes experience coupled stimulation of hydrostatic pressure (HP) and a transient increase in temperature (T), with the latter varying within a physiological range from 32.5 °C to 38.7 °C. Previous short-term in vitro studies have demonstrated that the combined HP-T stimuli more significantly enhance chondroinduction and chondroprotection of chondrocytes than isolated applications. Interestingly, this combined benefit is associated with a corresponding increase in HSP70 levels when HP and T are combined. The current study therefore explored the indispensable role of HSP70 in mediating the combined effects of HP-T stimuli on chondrocytes.DesignIn this mid-long-term study of in vitro engineered cartilage constructs, we assessed chondrocyte responses to HP-T stimuli using customized bioreactor in standard and HSP70-inhibited cultures.ResultsSurprisingly, under HSP70-inhibited conditions, the usually beneficial HP-T stimuli, especially its thermal component, exerted detrimental effects on chondrocyte homeostasis, showing a distinct and unfavorable shift in gene and protein expression patterns compared to non-HSP70-inhibited settings. Such effects were corroborated through mechanical testing and confirmed using a secondary cell source. A proteomic-based mechanistic analysis revealed a disruption in the balance between biosynthesis and fundamental cellular structural components in HSP70-inhibited conditions under HP-T stimuli.ConclusionsOur results highlight the critical role of sufficient HSP70 induction in mediating the beneficial effects of coupled HP-T stimulation on chondrocytes. These findings help pave the way for new therapeutic approaches to enhance physiotherapy outcomes and potentially shed light on the elusive mechanisms underlying the onset of cartilage degeneration, a long-standing enigma in orthopedics.

Cartilage repair remains a major challenge in human orthopedic medicine, necessitating the application of innovative strategies to overcome existing technical and clinical limitations. Adhesive hydrogels have emerged as promising candidates for cartilage repair promotion and tissue engineering, offering key advantages such as enhanced tissue integration and therapeutic potential. This comprehensive review navigates the landscape of adhesive hydrogels in cartilage repair, discussing identified challenges, shortcomings of current treatment options, and unique advantages of adhesive hydrogel products and scaffolds. While emphasizing the critical need for in situ lateral integration with surrounding tissues, we dissect current limitations and outline future perspectives for hydrogel scaffolds in cartilage repair. Moreover, we examine the clinical translation pathway and regulatory considerations specific to adhesive hydrogels. Overall, this review synthesizes the existing insights and knowledge gaps and highlights directions for future research regarding adhesive hydrogel-based devices in advancing cartilage tissue engineering.

This study proposes a novel dual adhesive approach for fixing osteochondral fractures, aiming to address the limitations of current fixation methods by incorporating both a bone adhesive (phosphoserine modified calcium phosphate cement PM-CPC) and a cartilage adhesive (methacrylated phosphoserine-containing gelatin MePGa hydrogel). The feasibility and efficacy of this approach were investigated using an ex vivo bovine knee model. Results indicate successful gluing of osteochondral cylinders with both adhesives, with no significant difference in adhesion strength between the groups (adhesion strength mean of 1211.6 kPa, SD 602.4 kPa, and mean of 1299.6 kPa, SD 850.9 kPa for groups 1 and 2 respectively). Importantly, the inclusion of the hydrogel component in the dual adhesive system aims to enhance cartilage repair potential, complementing the mechanical support provided by the bone adhesive. Each adhesive offers distinctive benefits: PM-CPC for mechanical support and bone repair, and MePGa hydrogel for cartilage repair. The study demonstrates the potential of the dual adhesive strategy for osteochondral repair, though further refinement and in vivo validation are needed.

Abstract Background In contact sports, an impact on the jaw can generate destructive stress on the tooth-bone system. Mouthguards can be beneficial in reducing the injury risk by changing the dynamics of the trauma. The material properties of mouthguards and their geometrical/structural attributes influence their protective performance. Custom-made mouthguards are the gold standard, and different configurations have been proposed to improve their protection and comfort. However, the effects of different design variables on the performance of customized mouthguards are not well understood. Results Herein, we developed a reliable finite element model to analyze contributing factors to the design of custom-made mouthguards. Accordingly, we evaluated the isolated and combined effect of layers’ stiffness, thickness, and space inclusion on the protective capability of customized mouthguards. Our simulations revealed that a harder frontal region could distribute load and absorb impact energy through bending if optimally combined with a space inclusion. Moreover, a softer layer could enlarge the time of impact and absorb its energy by compression. We also showed that mouthguards present similar protection with either permanently bonded or mechanically interlocked components. We 3D-printed different mouthguards with commercial resins and performed impact tests to experimentally validate our simulation findings. The impact tests on the fabricated mouthguards used in this work revealed that significantly higher dental protection could be achieved with 3D-printed configurations than conventionally fabricated customized mouthguards. In particular, the strain on the impacted incisor was attenuated around 50% more with a 3D-printed mouthguard incorporating a hard insert and space in the frontal region than a conventional Playsafe® Heavypro mouthguard. Conclusions The protective performance of a mouthguard could be maximized by optimizing its structural and material properties to reduce the risk of sport-related dental injuries. Combining finite element simulations, additive manufacturing, and impact tests provides an efficient workflow for developing functional mouthguards with higher protectiveness and athlete comfort. We envision the future with 3d-printed custom-mouthguards presenting distinct attributes in different regions that are personalized by the user based on the sport and associated harshness of the impact incidences.

Dissipative materials are essential for mitigating impact in various automotive, aerospace, and sports equipment applications. This study investigates the efficiency of a novel hybrid iono-organogel in dissipating and absorbing impact energies. The gel consists of a covalently cross-linked poly(acrylic acid)-co-poly(zwitterionic (DMAPS)) in a hybrid solvent system composed of the ionic liquid [C2OHMIM][BF4] and the oligomer PEG200. The optimal solvent hybridization ratio for achieving the lowest deceleration during impact testing is 40 vol % of the ionic liquid and 60 vol % of PEG200. The gel exhibits efficient mechanical dissipative properties with a loss factor exceeding 0.5 when solicited under various dynamic conditions with this optimized ratio. Moreover, the gel demonstrates high strength and toughness, enabling it to withstand impacts without experiencing catastrophic failure. The developed gel presents stable mechanical properties over broad temperature (0-100 °C) and frequency (0.01-2000 Hz) ranges. It maintains its performance during successive impacts, thanks to its self-recovery abilities. The remarkable mechanical properties of the gel are attributed to the abundance of combined functional groups within the gel polymeric network. Indeed, reversible H-bonds, ion-dipole, and dipole-dipole interactions were observed in different studies to enhance mechanical performance. Their unique synergy effect in the developed hybrid gels held promise for better control of impact properties and durability in numerous dynamic applications.

Deep learning models (DLM) are efficient replacements for computationally intensive optimization techniques. Musculoskeletal models (MSM) typically involve resource-intensive optimization processes for determining joint and muscle forces. Consequently, DLM could predict MSM results and reduce computational costs. Within the total shoulder arthroplasty (TSA) domain, the glenohumeral joint force represents a critical MSM outcome as it can influence joint function, joint stability, and implant durability. Here, we aimed to employ deep learning techniques to predict both the magnitude and direction of the glenohumeral joint force. To achieve this, 959 virtual subjects were generated using the Markov-Chain Monte-Carlo method, providing patient-specific parameters from an existing clinical registry. A DLM was constructed to predict the glenohumeral joint force components within the scapula coordinate system for the generated subjects with a coefficient of determination of 0.97, 0.98, and 0.98 for the three components of the glenohumeral joint force. The corresponding mean absolute errors were 11.1, 12.2, and 15.0 N, which were about 2% of the maximum glenohumeral joint force. In conclusion, DLM maintains a comparable level of reliability in glenohumeral joint force estimation with MSM, while drastically reducing the computational costs.