Chitosan Poly(vinyl alcohol) Methacrylate Hydrogels for Tissue Engineering Scaffolds.

A major challenge in tissue engineering scaffolds is controlling scaffold degradation rates during healing while maintaining mechanical properties to support tissue formation. Hydrogels are three-dimensional matrices that are widely applied as tissue scaffolds based on their unique properties that can mimic the extracellular matrix. In this study, we develop a hybrid natural/synthetic hydrogel platform to tune the properties for tissue engineering scaffold applications. We modified chitosan and poly(vinyl alcohol) (PVA) with photo-cross-linkable methacrylate functional groups and then synthesized a library of chitosan PVA methacrylate hydrogels (ChiPVAMA) with two different photoinitiators, Irgacure 2959 (I2959) and lithium phenyl-2,4,6-trimethylbenzoylphosphinate (LAP). ChiPVAMA hydrogels showed tunability in degradation rates and mechanical properties based on both the polymer content and photoinitiator type. This tunability could enable their application in a range of tissue scaffold applications. In a 2D scratch wound healing assay, all hydrogel samples induced faster wound closure compared to a gauze clinical wound dressing control. NIH/3T3 cells encapsulated in hydrogels showed a high viability (∼92%) over 14 days, demonstrating the capacity of this system as a supportive cell scaffold. In addition, hydrogels containing a higher chitosan content demonstrated a high antibacterial capacity. Overall, ChiPVAMA hydrogels provide a potential tissue engineering scaffold that is tunable, degradable, and suitable for cell growth.

Study on the use of 3D printed guides in the individualized reconstruction of the anterior cruciate ligament.

OBJECTIVE: Evaluation of the accuracy and effectiveness of 3D printed guides to assist femoral tunnel preparation in individualised reconstruction of the anterior cruciate ligament. METHODS: Sixty patients who attended the Affiliated Hospital of Binzhou Medical College for autologous hamstring single bundle reconstruction of the anterior cruciate ligament from October 2018 to October 2020 were selected and randomly divided into two groups, including 31 cases in the 3D printing group (14 males and 17 females, mean age 41.94 ± 10.15 years) and 29 cases in the control group (13 males and 16 females, mean age 37.76 ± 10.34 years). Patients in both groups were assessed for intraoperative femoral tunnel accuracy, the number of intraoperative positioning and the time taken to prepare the femoral tunnel, the length of the anteromedial approach incision, the pre-planned bone tunnel length and intraoperative bone tunnel length in the 3D printed group, IKDC score and Lysholm score preoperatively and at 3, 6 and 12 months postoperatively, the Lachman、pivot-shift test preoperatively and at 6 months postoperatively, gait analysis to assess internal and external rotation in flexion of the knee at 12 months postoperatively and postoperative complications in both groups. RESULTS: There was no statistical difference in functional knee scores and anteromedial approach incision length between the 3D printed and control groups (p > 0.05), while there was a statistical difference in the accuracy of tunnel positioning, the time taken to prepare the femoral bone tunnel and the degree of external rotation of the knee in flexion between the two groups (p < 0.05). There was no statistical difference between the preoperative planning of the bone tunnel length and the intraoperative bone tunnel length (p > 0.05). COMPLICATIONS: One case in the 3D printing group developed intermuscular vein thrombosis in the affected lower limb after surgery, which disappeared after treatment, while three cases in the control group developed intermuscular vein thrombosis in the affected lower limb. No complications such as bone tunnel rupture, deep vein thrombosis in the lower limb and infection occurred in either group. CONCLUSION: 3D printed guides assisted with individualized ACL reconstruction may improve the accuracy of femoral tunnel positioning, which is safe and effective, while reducing the operative time and the number of intraoperative positioning, without increasing the length of incision, and may obtain higher functional scores and rotational stability of the knee joint, which is in line with the concept of individualized ACL reconstruction.

Self-Defensive Antimicrobial Shape Memory Polyurethanes with Honey-Based Compounds.

Infection treatment plays a crucial role in aiding the body in wound healing. To that end, we developed a library of antimicrobial polymers based on segmented shape memory polyurethanes with nondrug-based antimicrobials (i.e., honey-based phenolic acids (PAs)) using both chemical and physical incorporation approaches. The antimicrobial shape memory polymers (SMPs) have high transition temperatures (>55 °C) to enable maintenance of temporary, programmed shapes in physiological conditions unless a specific external stimulus is present. Polymers showed tunable mechanical and shape memory properties by changing the ratio, chemistry, and incorporation method of PAs. Cytocompatible (∼100% cell viability) synthesized polymers inhibited growth rates of Staphylococcus aureus (∼100% with physically incorporated PAs and >80% with chemically incorporated PAs) and Escherichia coli (∼100% for samples with cinnamic acid (physical and chemical)). Crystal violet assays showed that all formulations inhibit biofilm formation in surrounding solutions, and chemically incorporated samples showed surface antibiofilm properties with S. aureus. Molecular dynamics simulations confirm that PAs have higher levels of interactions with S. aureus cell membranes than E. coli. Long-term antimicrobial properties were measured after storage of the sample in aqueous conditions; the polymers retained their antimicrobial properties against E. coli after up to 20 days. As a proof of concept, magnetic particles were incorporated into the polymer to trigger user-defined shape recovery by applying an external magnetic field. Shape recovery disrupted preformed S. aureus biofilms on polymer surfaces. This antimicrobial biomaterial platform could enable user- or environmentally controlled shape change and/or antimicrobial release to enhance infection treatment efforts.

Dual Burst and Sustained Release of p-Coumaric Acid from Shape Memory Polymer Foams for Polymicrobial Infection Prevention in Trauma-Related Hemorrhagic Wounds.

Hemorrhage is the primary cause of trauma-related death. Of patients that survive, polymicrobial infection occurs in 39% of traumatic wounds within a week of injury. Moreover, traumatic wounds are susceptible to hospital-acquired and drug-resistant bacterial infections. Thus, hemostatic dressings with antimicrobial properties could reduce morbidity and mortality to enhance traumatic wound healing. To that end, p-coumaric acid (PCA) was incorporated into hemostatic shape memory polymer foams by two mechanisms (chemical and physical) to produce dual PCA (DPCA) foams. DPCA foams demonstrated excellent antimicrobial and antibiofilm properties against native Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis; co-cultures of E. coli and S. aureus; and drug-resistant S. aureus and S. epidermidis at short (1 h) and long (7 days) time points. Resistance against biofilm formation on the sample surfaces was also observed. In ex vivo experiments in a porcine skin wound model, DPCA foams exhibited similarly high antimicrobial properties as those observed in vitro, indicating that PCA was released from the DPCA foam to successfully inhibit bacterial growth. DPCA foams consistently showed improved antimicrobial properties relative to those of clinical control foams containing silver nanoparticles (AgNPs) against single and mixed species bacteria, single and mixed species biofilms, and bacteria in the ex vivo wound model. This system could allow for physically incorporated PCA to first be released into traumatic wounds directly after application for instant wound disinfection. Then, more tightly tethered PCA can be continuously released into the wound for up to 7 days to kill additional bacteria and protect against biofilms.

In vitro and in vivo degradation correlations for polyurethane foams with tunable degradation rates.

Polyurethane foams present a tunable biomaterial platform with potential for use in a range of regenerative medicine applications. Achieving a balance between scaffold degradation rates and tissue ingrowth is vital for successful wound healing, and significant in vivo testing is required to understand these processes. Vigorous in vitro testing can minimize the number of animals that are required to gather reliable data; however, it is difficult to accurately select in vitro degradation conditions that can effectively mimic in vivo results. To that end, we performed a comprehensive in vitro assessment of the degradation of porous shape memory polyurethane foams with tunable degradation rates using varying concentrations of hydrogen peroxide to identify the medium that closely mimics measured in vivo degradation rates. Material degradation was studied over 12 weeks in vitro in 1%, 2%, or 3% hydrogen peroxide and in vivo in subcutaneous pockets in Sprague Dawley rats. We found that the in vitro degradation conditions that best predicted in vivo degradation rates varied based on the number of mechanisms by which the polymer degraded and the polymer hydrophilicity. Namely, more hydrophilic materials that degrade by both hydrolysis and oxidation require lower concentrations of hydrogen peroxide (1%) to mimic in vivo rates, while more hydrophobic scaffolds that degrade by oxidation alone require higher concentrations of hydrogen peroxide (3%) to model in vivo degradation. This information can be used to rationally select in vitro degradation conditions that accurately identify in vivo degradation rates prior to characterization in an animal model.

Shape Memory Polymer Foams with Phenolic Acid-Based Antioxidant Properties.

Phenolic acids (PAs) are natural antioxidant agents in the plant kingdom that are part of the human diet. The introduction of naturally occurring PAs into the network of synthetic shape memory polymer (SMP) polyurethane (PU) foams during foam fabrication can impart antioxidant properties to the resulting scaffolds. In previous work, PA-containing SMP foams were synthesized to provide materials that retained the desirable shape memory properties of SMP PU foams with additional antimicrobial properties that were derived from PAs. Here, we explore the impact of PA incorporation on SMP foam antioxidant properties. We investigated the antioxidant effects of PA-containing SMP foams in terms of in vitro oxidative degradation resistance and cellular antioxidant activity. The PA foams showed surprising variability; p-coumaric acid (PCA)-based SMP foams exhibited the most potent antioxidant properties in terms of slowing oxidative degradation in H2O2. However, PCA foams did not effectively reduce reactive oxygen species (ROS) in short-term cellular assays. Vanillic acid (VA)- and ferulic acid (FA)-based SMP foams slowed oxidative degradation in H2O2 to lesser extents than the PCA foams, but they demonstrated higher capabilities for scavenging ROS to alter cellular activity. All PA foams exhibited a continuous release of PAs over two weeks. Based on these results, we hypothesize that PAs must be released from SMP foams to provide adequate antioxidant properties; slower release may enable higher resistance to long-term oxidative degradation, and faster release may result in higher cellular antioxidant effects. Overall, PCA, VA, and FA foams provide a new tool for tuning oxidative degradation rates and extending potential foam lifetime in the wound. VA and FA foams induced cellular antioxidant activity that could help promote wound healing by scavenging ROS and protecting cells. This work could contribute a wound dressing material that safely releases antimicrobial and antioxidant PAs into the wound at a continuous rate to ideally improve healing outcomes. Furthermore, this methodology could be applied to other oxidatively degradable biomaterial systems to enhance control over degradation rates and to provide multifunctional scaffolds for healing.

Shape Memory Polymer Foams With Phenolic Acid-Based Antioxidant and Antimicrobial Properties for Traumatic Wound Healing.

The leading cause of trauma-related death before arrival at a hospital is uncontrolled blood loss. Upon arrival at the hospital, microbial infections in traumatic wounds become an additional factor that increases mortality. The development of hemostatic materials with antimicrobial and antioxidant properties could improve morbidity and mortality in these wounds. To that end, phenolic acids (PAs) were successfully incorporated into the network of shape memory polymer (SMP) polyurethane foams by reacting them with isocyanates. Resulting PA-containing SMP foam shape memory properties, antimicrobial and antioxidant activity, and blood and cell interactions were characterized. Results showed that p-coumaric, vanillic, and ferulic acids were successfully incorporated into the SMP foams. The PA-containing SMP foams retained the antimicrobial and antioxidant properties of the incorporated PAs, with ∼20% H2O2 scavenging and excellent antimicrobial properties again E. coli (∼5X reduction in CFUs vs. control foams), S. aureus (∼4.5X reduction in CFUs vs. control foams, with comparable CFU counts to clinical control), and S. epidermidis (∼25-120X reduction in CFUs vs. control foams, with comparable CFU counts to clinical control). Additionally, appropriate thermal and shape memory properties of PA foams could enable stable storage in low-profile secondary geometries at temperatures up to ∼55°C and rapid expand within ∼2 min after exposure to water in body temperature blood. PA foams had high cytocompatibility (>80%), non-hemolytic properties, and platelet attachment and activation, with improved cytocompatibility and hemocompatibility in comparison with clinical, silver-based controls. The incorporation of PAs provides a natural non-antibiotic approach to antimicrobial SMP foams with antioxidant properties. This system could improve outcomes in traumatic wounds to potentially reduce bleeding-related deaths and subsequent infections.

Characterization of Phenolic Acid Antimicrobial and Antioxidant Structure-Property Relationships.

Keywords: phenolic acids; antimicrobial; antioxidant.

Three-Dimensional Reconstruction Modeling of the Spatial Displacement, Extent and Rotational Orientation of Undisplaced Femoral Neck Fractures.

The purpose of this study was to employ a new three-dimensional (3D) reconstruction and modeling method to measure displacement of undisplaced femoral neck fractures (Garden stages I and II). We also aimed to evaluate the effectiveness of the Garden classification for determining the displacement of undisplaced femoral neck fractures. A total of 120 consecutive patients with undisplaced femoral neck fractures were enrolled between 2012 and 2014, including 60 within the Garden I group and 60 within the Garden II group. The displacements of the femoral head center (d1) and the lowest point of the fovea capitis femoris (d2) and rotational displacement of the femoral head (α) in the 3D model were measured with 3D computed tomography reconstruction and modeling. Five observers, trauma surgeons, were asked to found the centers of the femoral heads and the deepest points of the foveae. The intraobserver and inter-observer agreements were calculated using Fleiss' kappa. The inter-observer and intra-observer kappa values were 0.937 and 0.985, respectively. Current method has good reliability. We discovered that many participants in our study had been misclassified by an anterior-posterior radiograph as having an "incomplete" fracture. In incomplete fracture of Garden stage I group, the average displacements d1 and d2 were 3.69 ± 1.77 mm and 14.51 ± 1.91 mm, respectively. The mean α was 4.91° ± 2.49°. For impacted fracture of Garden stage I, significant spatial displacement in the impacted fractures was observed (d1: 6.22 ± 3.36 mm; d2: 10.30 ± 5.73 mm; and α: 17.83° ± 10.72°). Similarly, significant spatial displacement was observed among the Garden stage II group (d1: 7.16 ± 4.58 mm; d2: 12.95 ± 8.25 mm; and α: 18.77° ± 9.10°). There was no significant difference in α, d1, and d2 between impacted fracture and Garden stage II groups (P > 0.05). However, significant differences were found between incomplete fracture and Garden stage II groups (P < 0.05). Our findings suggest that 3D reconstruction and modeling may be a better tool for assessing femoral neck fractures than the Garden classification. Undisplaced femoral neck fractures showed variable degrees of displacement and were not undisplaced, stable fractures. Garden classification for undisplaced femoral neck fractures has certain limitations.

Biomechanical comparison of mono-segment transpedicular fixation with short-segment fixation for treatment of thoracolumbar fractures: a finite element analysis.

Mono-segment transpedicular fixation is a method for the treatment of certain types of thoracolumbar spinal fracture. Finite element models were constructed to evaluate the biomechanics of mono-segment transpedicular fixation of thoracolumbar fracture. Spinal motion (T10-L2) was scanned and used to establish the models. The superior half of the cortical bone of T12 was removed and the superior half of the cancellous bone of the T12 body was assigned the material properties of injured bone to mimic vertebral fracture. Transpedicular fixation of T11 and T12 was performed to produce a mono-segment fixation model; T11 and L1 were fixed to produce a short-segment fixation model. Motion differences between functional units and von Mises stress on the spine and implants were measured under axial compression, anterior bending, extensional bending, lateral bending and axial rotation. We found no significant difference between mono- and short-segment fixations in the motion of any functional unit. Stress on the T10/T11 nucleus pulposus and T10/T11 and L1/L2 annulus fibrosus increased significantly by about 75% on anterior bending, extensional bending and lateral bending. In the fracture model, stress was increased by 24% at the inferior endplate of T10 and by 43% at the superior endplate of L2. All increased stresses were reduced after fixation and lower stress was observed with mono-segment fixation. In summary, the biomechanics of mono-segment pedicle screw instrumentation was similar to that of conventional short-segment fixation. As a minimally invasive treatment, mono-segment fixation would be appropriate for the treatment of selected thoracolumbar spinal fractures.

Reunderstanding of garden type I femoral neck fractures by 3-dimensional reconstruction.

Garden type I fractures include incomplete fractures and impacted fractures. With advances in scientific technology and medical treatment, certain deficiencies of the Garden classification have become apparent. The authors hypothesized that the incidence of incomplete femoral neck fractures was low and that impacted femoral neck fractures were not undisplaced and stable fractures. A new method was developed to precisely measure the spatial displacement of the femoral head in impacted femoral neck fractures. Between 2008 and 2011, nine hundred sixty-six patients with femoral neck fractures were treated, 48 of whom had Garden type I fractures, as seen on anteroposterior radiographs. Seven fractures were classified as incomplete on radiographs; however, after 3-dimensional reconstruction, 3 were classified as incomplete and 4 as complete fractures. Furthermore, the remaining 41 Garden I fractures that were classified as impacted on radiographs showed large spatial displacement on 3-dimensional reconstruction. The average rotational displacement of the femoral head was 19.29°±10.51°, and the average displacements of the femoral head center and the lowest point of the fovea capitis were 8.76±4.45 and 14.39±8.08 mm, respectively. This study showed that the incidence of incomplete femoral neck fractures was low. Impacted femoral neck fractures showed variable degrees of displacement and were not undisplaced, stable fractures. Garden classification for impacted femoral neck fractures has certain limitations. Impacted femoral neck fractures should be differentiated from Garden type I fractures so clinicians can select appropriate treatments for these fractures.

[Three-dimensional reconstruction study of the displacement of undisplaced femoral neck fractures].

OBJECTIVE: To measure the displacement parameters of femoral head in space through three-dimensional reconstruction so as to reunderstand undisplaced femoral neck fractures. METHODS: The clinical data of 80 undisplaced femoral neck fractures from January 2010 to June 2011 were selected, included Garden I 40 cases (group Garden I) and Garden II 40 cases (group Garden II), bilateral proximal femurs of everyone were scanned by CT and reconstructed by professional software. Registered the normal femur and fracture with mirror model, marked key points in the model and measured the displacement parameters of femoral head. The measurement accuracy of distance and angle were 0.01 mm and 0.01°, respectively. The parameters of femoral head displacement between group Garden I and Garden II were analyzed by independent-sample t-test. RESULTS: Eighty cases on X-ray films were not found rotated displacement. But 24 cases of them (30.0%) showed rotated displacement and rotation direction of the femoral head through three-dimensional reconstruction. Ten cases showed incomplete fractures on X-ray films, but only 3 cases were incomplete fractures with three-dimensional reconstruction. In group Garden I, the femoral head displacement angle was 18° ± 11°, the average displacement distance of femoral head center and deepest point of fovea capitis were (6 ± 3) mm and (10 ± 6) mm respectively. In group Garden II, the femoral head displacement angle was 17° ± 10°, the average displacement distance of femoral head center and deepest point of fovea capitis were (7 ± 5) mm and (13 ± 8) mm respectively. There were not statistical significance of the parameters of femoral head displacement between group Garden I and Garden II (P > 0.05). CONCLUSIONS: Three-dimensional reconstruction and digital measurement is a precise, efficient method for the measurement of femoral head displacement parameters in femoral neck fractures, has important clinical significance in the diagnosis and treatment of the femoral neck fractures. There are certain defects and limitations of the classical Garden classification for undisplaced femoral neck fractures.