Defect Model Research Articles

Fabrication of MnO2-Modified Decellularized Tendon Membrane for Enhancing Tendon Repair.

Repairing tendon/ligament injuries is a major challenge in sports medicine. It has been reported that tendon injury healing is hindered by massive production of reactive oxygen species (ROS). Manganese oxides nanoparticles are generally non-toxic, can scavenge ROS, promote tissue regeneration, and hold promise for sustainable nanotechnologies. However, the effective and safe integration of MnO2 nanoparticles on decellularized scaffold mediating tissue repair is still a great challenge. To address these issues, an in situ MnO2-modified decellularized scaffold is developed to enhance tendon regeneration through improving microenvironment. The decellularized fibrous membrane is designed and prepared using the central tendon of the porcine diaphragm. Then MnO2 nanozymes are in situ grown on the collagen fibers using tannic acid (TA) as cross-linking agent and reducing agent. The results showed that MnO2-modified scaffold eliminates excessive accumulation of ROS in cells, protects mitochondrial, and maintains the phenotype of tendon cells in an oxidative stress environment. Notably, it is found that the MnO2-modified scaffold exhibits good biocompatibility and is able to promote the tendon healing in the rat patellar tendon defect model. Altogether, this study confirmed that this nanozyme-functionalized decellularized extracellular matrix effectively enhanced tendon repair by scavenging ROS, which provides new strategies for enhancing tendon regeneration.

Image reconstruction from compressed measurements for ultrasound NDT

In ultrasound NDT, Delay-and-Sum schemes are commonly used to reconstruct images from the measurement data. For single channel pulse-echo measurements, this is called Synthetic Aperture Focusing Technique (SAFT). In a multi-channel setup, SAFT is extended to the Total Focusing Method (TFM), where the focused image is reconstructed from measurements of all transmit-receive combinations, called Full Matrix Capture (FMC). In previous work, we showed that both SAFT and TFM can be cast as a sparse recovery problem that enables enhancing the Delay-and-Sum scheme to a physically motivated forward model that leads to improved image quality. The reconstruction is performed using l1 minimization. Further, this also allows to perform the reconstruction from compressed/subsampled measurements following compressed sensing theory. This subsampling was achieved by only measuring a subset of the frequency coefficients of the signal. In both the single channel and the multi-channel setup the amount of measurement data is thereby significantly reduced. Additionally, for the TFM, we added a spatial subsampling by only considering a subset of transmit and receive pairs, further reducing the measurement data and at the same time also reducing the measurement time. In our previous work, the frequency and spatial dimensions were considered separately for simplicity, using the same compression strategy for all spatial measurements. In this work we consider joint frequency/spatial compression schemes. We show that a joint multidimensional compression strategy where different Fourier subsets are considered for each channel pair leads to a superior reconstruction performance when the compression rate is fixed. Analysis based on an analytical model for a single defect and a real-world example with multiple defects shows that the approach works in practice.

Early signs of osteoarthritis in differing rat osteochondral defects.

Preclinical models of osteochondral defects (OCDs) are fundamental test beds to evaluate treatment modalities before clinical translation. To increase the rigor and reproducibility of translational science for a robust "go or no-go," we evaluated disease progression and pain phenotypes within the whole joint for two OCD rat models with same defect size (1.5x 0.8 mm) placed either in the trochlea or medial condyle of femur. Remarkably, we only found subtle transitory changes to gaits of rats with trochlear defect without any discernible effect to allodynia. At 8-weeks post-surgery, anatomical evaluations of joint showed early signs of osteoarthritis with EPIC-microCT. For the trochlear defect, cartilage attenuation was increased in trochlear, medial, and lateral compartments of the femur. For condylar defect, increased cartilage attenuation was isolated to the medial condyle of the femur. Further, the medial ossicle showed signs of deterioration as indicated with decreased bone mineral density and increased bone surface area to volume ratio. Thus, OCD in a weight-bearing region of the femur gave rise to more advanced osteoarthritis phenotype within a unilateral joint compartment. Subchondral bone remodeling was evident in both models without any indication of closure of the articular cartilage surface. We conclude that rat OCD, placed in the trochlear or condylar region of the femur, leads to differing severity of osteoarthritis progression. As found herein, repair of the defect with fibrous tissue and subchondral bone is insufficient to alleviate onset of osteoarthritis. Future therapies using rat OCD model should address joint osteoarthritis in addition to repair itself.

Enhancing Bone-Titanium integration through hydrogel coating mediated sequential M1/M2 polarization of interfacial macrophages

Regulating phenotypes of in situ macrophages (Mφ) is a cutting-edge strategy for promoting bone-Titanium (Ti) integration, but what is the most rational modulation manner has long been controversial. Short-term inducing in situ M1 Mφ polarization or inducing in situ M2 Mφ polarization have proven to be capable of promoting osseointegration. However, an increasing number of researches have claimed that sequentially inducing in situ M1/M2 Mφ polarization, compared to the above-mentioned two strategies, could further enhance osseointegration. In this work, we compared the capability of the three different modulation manners to promote osseointegration. Briefly, we anchored a homogeneous Poly(HEMA-co-3APBA)/LUT/SOP hydrogel coating, which could sequentially release pro-inflammatory sophoridine (SOP) molecules and anti-inflammatory luteolin (LUT) molecules through pH mediated conformational transition of phenylboronic acid ester bonds, on the surface of Ti implants. Ti implants coated with the Poly(HEMA-co-3APBA)/SOP hydrogel or the Poly(HEMA-co-3APBA)/LUT hydrogel, which merely released SOP molecules and LUT molecules respectively, were utilized as controls. In vitro Mφ co-culture assays proved the immunoregulation functions of different hydrogel coatings in inducing Mφ polarization, and the rationale behind which was identified to be related to the PI3K-AKT signaling pathways. In addition, the immunoregulation mediated osteogenic differentiation behaviors of bone marrow mesenchymal stem cells (BMSCs) were also investigated. Implantation of as-prepared Ti nails to a rat femur defect model followed by evaluations of H&E staining, Masson staining, immunohistochemical staining, etc. proved the stronger capability to enhance osseointegration of inducing sequential M1/M2 Mφ polarization than short-term inducing in situ M1 Mφ polarization or inducing in situ M2 Mφ polarization. This work not only reported a novel Ti implant with superior osseointegration capability but also will inspire corresponding researches in the future.

Stem cell-homing biomimetic hydrogel promotes the repair of osteoporotic bone defects through osteogenic and angiogenic coupling.

Osteoporotic bone defects refer to the disruption of bone structural integrity in patients with osteoporosis and pose a substantial challenge to orthopedic surgeons. In this study, we developed a biomimetic hydrogel to improve the osteogenic microenvironment and promote stem cell homing. This hydrogel served as a container for S-nitrosoglutathione and Ca2+, promoting the release of bioactive nitric oxide (NO) from bone marrow mesenchymal stem cells (BMSCs) and human vascular endothelial cells and activating the NO/cyclic guanosine monophosphate signaling pathway. These changes promote osteogenic and angiogenic couplings. The hydrogel simultaneously recruited BMSCs by conjugating the stem cell homing peptide SKPPGTSS. Using a rat distal femoral defect model, it was demonstrated that this hydrogel can effectively increase the formation of bone tissue and new blood vessels and has immune-regulating functions. We envision that this hydrogel may be a minimally invasive yet highly effective strategy for expediting the healing of osteoporotic bone defects.

Unveiling the effect of bovine serum albumin on the corrosion resistance of high nitrogen stainless steel for cardiac stents

Herein, the effect of bovine serum albumin (BSA) on the corrosion resistance of high nitrogen stainless steel (HNS) is systematically investigated based on experimental characterizations and first-principle calculations. Electrochemical measurements firstly prove that the anodic dissolution rate of HNS has significantly increased due to BSA adsorption and the potential deterioration of the passive film. By subsequent morphology and composition characterizations, it is demonstrated that BSA forms a 1.9 μm porous adsorption layer on HNS surface via the peptide bond mostly in -helix and -turn structure. Furthermore, Mott-Schottky tests confirm that the carrier (cation vacancy) density in the passive film has dramatically risen from 6.29×1021 cm-3 to 1.97×1022 cm-3 after BSA adsorption, which could be ascribed to the detachment of Cr atom from its original lattice due to the preference interaction between BSA molecule and Cr atom. Most importantly, such an increased defects will further promote the dissolution process of both the passive film and HNS matrix according to point defect model (PDM), which will definitely undermine the protective ability of the passive film and eventually result in the declined corrosion resistance of HNS in BSA-contained solution.

Study on the damage characteristics of high-temperature superconducting cable insulation under air gap discharge

This study explores the impact of small air gaps in high-temperature superconducting cables on the insulating material polypropylene-laminated paper (PPLP), and the aging rules and mechanisms of the insulating material during practical uses. An air gap discharge test platform was built to simulate air gap fault defects of superconducting cables in the real operating environment. Hierarchical clustering method was used to divide the gap discharge process of defect model into four stages. Insulation damage assessment was conducted on the intermediate layer PP of the superconducting insulation material PPLP at different discharge stages, revealing surface changes and periodic alterations in dielectric properties. The morphological features, roughness, infrared spectra, dielectric loss, surface resistivity, and other phase characteristics of the superconducting insulation layer material were analyzed at different stages of air gap defects. Molecular group cracking in PP was attributed to the bond breakage on the main chain. These findings provide insights into high-temperature superconducting cable insulation under air gap discharge and provide a guideline for practical applications in semi-conductive industries.

Experimental Study on Quick‐Locking Reinforcement Model for Local Defects in Pipelines in the Rich Water Area

ABSTRACTThe management of local defects in municipal pipelines in water‐rich areas remains a significant challenge, particularly under high‐pressure conditions. This study investigates the performance of quick‐lock steel sleeves as a trenchless repair method through full‐scale experiments on five different pipeline diameters. The experiments focus on the failure modes and critical buckling pressure of the sleeves under external pressure. A novel design model based on structural reliability theory was developed and validated against experimental results. The results show a close match between the calculated and experimental buckling pressures, with a ratio ranging from 0.87 to 1.15. These findings provide valuable insights for the design and application of quick‐lock sleeves in high‐pressure municipal networks. This study contributes to improving the reliability and effectiveness of pipeline repair technologies, offering practical solutions for addressing pipeline leakage and instability in challenging environments.

Healthy but not osteoarthritic human meniscus-derived matrix scaffolds promote meniscus repair.

Meniscus tissue is commonly injured due to sports-related injuries and age-related degeneration and approximately 50% of individuals with a meniscus tear will develop post-traumatic osteoarthritis (PTOA). Given that the meniscus has limited healing potential, new therapeutic strategies are required to enhance meniscus repair. Porcine meniscus-derived matrix (MDM) scaffolds improve meniscus integrative repair, but sources of human meniscus tissue have not been investigated. Therefore, the objectives of this study were to generate healthy and osteoarthritic (OA) MDM scaffolds and to compare meniscus cellular responses and integrative repair. Meniscus cells showed high viability on both healthy and OA scaffolds. While DNA content was higher in cell-seeded OA scaffolds than cell-seeded healthy scaffolds, CCK-8, and both sGAG and collagen content were similar between scaffold types. After 28days in an ex vivo meniscus defect model, healthy and OA scaffolds had similar DNA, sGAG, and collagen content. However, the shear strength of repair was reduced in defects containing OA scaffolds compared to healthy scaffolds. In conclusion, healthy human allograft tissue is a useful source for generating MDM scaffolds that can support cellular growth, ECM production, and ex vivo integrative repair of the meniscus, highlighting the potential suitability for tissue engineering approaches to improve meniscus repair.

Compositional Variations in Calcium Phosphate Cement and Poly(Lactic-Co-Glycolic-Acid) Porogens Do Not Affect the Orthotopic Performance of Calcium Phosphate Cement/Poly(Lactic-Co-Glycolic-Acid) Cements.

Calcium phosphate cement (CPC) has evolved as an appealing bone substitute material, especially since CPCs were combined with poly(lactic-co-glycolic acid) (PLGA) porogens to render the resulting CPC/PLGA composite degradable. In view of the multiple variables of CPC and PLGA used previously, the effect of CPC composition and PLGA porogen morphology (i.e., microspheres versus microparticles) on the biological performance of CPC/PLGA has not yet been investigated. Consequently, we here aimed to evaluate comparatively various CPC/PLGA formulations varying in CPC composition and PLGA porogen morphology on their performance in a rabbit femoral condyle bone defect model. CPCs with a composition of 85 wt% α-TCP, 15 wt% dicalcium phosphate anhydrate (DCPA) and 5 wt% precipitated hydroxyapatite (pHA), or 100 wt% α-TCP were combined with spherical or irregularly shaped PLGA porogens (CPC/PLGA ratio of 60:40 wt% for all formulations). All CPC/PLGA formulations were applied via injection in bone defects, as created in the femoral condyle of rabbits, and retrieved for histological evaluation after 6 and 12 weeks of implantation. Descriptive histology and quantitative histomorphometry (i.e., material degradation and new bone formation) were used for analyses. Descriptively, all CPC/PLGA formulations showed material degradation at the periphery of the cement within 6 weeks of implantation. After 12 weeks, bone formation was observed extending into the defect core, replacing the degraded CPC/PLGA material. Quantitatively, similar material degradation (up to 87%) and new bone formation (up to 28%) values were observed, irrespective of compositional variations of CPC/PLGA formulations. These data prove that neither the CPC compositions nor the PLGA porogen morphologies as used in this work affect the biological performance of CPC/PLGA formulations in a rabbit femoral condyle bone defect model.

Enhancing osteogenesis and mandibular defect repair with magnesium-modified acellular bovine bone matrix

An acellular bovine bone matrix modified to release Magnesium ions (Mg2+) (ABBM-Mg) was prepared and evaluated for its potential in osteogenesis and mandibular defect repair. Mg2+ was incorporated into ABBM using an ion exchange method. The microstructure and mechanical properties of both ABBM and ABBM-Mg were analyzed using SEM and a biomechanical testing machine. Cytocompatibility, cell adhesion, and osteogenic differentiation were assessed using various methods including CCK-8, Live/Dead staining, SEM, ALP staining, and qPCR analysis in MC3T3-E1 cells. Additionally, a mandibular defect model in rats was established. The bone defect repair outcomes were evaluated using Micro-CT, histological HE staining, and Masson staining. The study showed that mineralization containing magnesium was redeposited on the surface of the three-dimensional porous ABBM, and the ABBM-Mg scaffold promoted cell proliferation and osteogenic differentiation compared to the ABBM scaffold. In the rat mandibular defect model, the ABBM-Mg scaffold demonstrated superior bone repair ability. This study successfully incorporated Mg2+ into ABBM without significantly affecting its microstructure and compressive strength. Furthermore, ABBM-Mg showed sustained release of Mg2+ which enhanced cell proliferation, adhesion, and osteogenic differentiation in vitro, and promoted mandibular defect healing in rats. This research opens up new possibilities for the clinical application of functionalized acellular bone matrix.Graphical

Enhancing wound healing through innovative technologies: microneedle patches and iontophoresis.

Wound healing is a complex process involving multiple stages, including inflammation, proliferation, and remodeling. Effective wound management strategies are essential for accelerating healing and improving outcomes. The CELLADEEP patch, incorporating iontophoresis therapy and microneedle technology, was evaluated for its potential to enhance the wound healing process. This study utilized a full-thickness skin defect model in Sprague-Dawley rats, researchers compared wound healing outcomes between rats treated with the CELLADEEP Patch and those left untreated. Various histological staining techniques were employed to examine and assess the wound healing process, such as H&E, MT and immunofluorescence staining. Furthermore, the anti-inflammatory and proliferative capabilities were further investigated using biochemical assays. Macroscopic and microscopic analyses revealed that the CELLADEEP patch significantly accelerated wound closure, reduced wound width, and increased epidermal thickness and collagen deposition compared to an untreated group. The CELLADEEP patch decreased nitric oxide and reactive oxygen species levels, as well as pro-inflammatory cytokines IL-6 and TNF-α, indicating effective modulation of the inflammatory response. Immunofluorescence staining showed reduced markers of macrophage activity (CD68, F4/80, MCP-1) in the patch group, suggesting a controlled inflammation process. Increased levels of vimentin, α-SMA, VEGF, collagen I, and TGF-β1 were observed, indicating enhanced fibroblast activity, angiogenesis, and extracellular matrix production. The CELLADEEP patch demonstrated potential in promoting effective wound healing by accelerating wound closure, modulating the inflammatory response, and enhancing tissue proliferation and remodeling. The CELLADEEP patch offers a promising non-invasive treatment option for improving wound healing outcomes.

Supplemental Magnesium Gluconate Enhances Scaffold-Mediated New Bone Formation and Natural Bone Healing by Angiogenic- and Wnt Signal-Associated Osteogenic Activation.

Local implantation or supplementation of magnesium gluconate (MgG) is being investigated as an effective approach to bone repair. Although studies have highlighted the possible mechanisms in Mg ion-stimulated new bone formation, the role of MgG in healing bone defects and the signaling mechanisms are not yet completely understood. In this study, we explored how supplemental MgG has bone-specific beneficial effects by delivering MgG locally and orally in animal models. We fabricated MgG-incorporated (CMC-M) and -free chitosan (CMC) scaffolds with good microstructures and biocompatible properties. Implantation with CMC-M enhanced bone healing in rat model of mandible defects, compared with CMC, by activating Wnt signals and Wnt-related osteogenic and angiogenic molecules. Oral supplementation with MgG also stimulated bone healing in mouse model of femoral defects along with the increases in Wnt3a and angiogenic and osteogenic factors. Supplemental MgG did not alter nature bone accrual and bone marrow (BM) microenvironment in adult mouse model, but enhanced the functioning of BM stromal cells (BMSCs). Furthermore, MgG directly stimulated the induction of Wnt signaling-, angiogenesis-, and osteogenesis-related molecules in cultures of BMSCs, as well as triggered the migration of endothelial cells. These results suggest that supplemental MgG improves bone repair in a way that is synergistically enhanced by Wnt signal-associated angiogenic and osteogenic molecules. Overall, this study indicates that supplemental MgG might ameliorate oxidative damage in the BM, improve the functionality of BM stem cells, and maintain BM-microenvironmental homeostasis.

Multifunctional extracellular vesicles and edaravone-loaded scaffolds for kidney tissue regeneration by activating GDNF/RET pathway

With the severity of chronic kidney disease worldwide, strategies to recover renal function via tissue regeneration provide alternatives to kidney replacement therapy. To exclude side effects from direct cell transplantation, extracellular vesicles (EVs) are great substitutes representing paracrine cell signaling. To build three-dimensional structures for implantation into the 5/6 nephrectomy model by incorporating bioactive materials, including multifunctional EVs (mEVs), porous PMEZE/mEV scaffolds were developed in combination with edaravone (EDV; E) and mEV based on PMEZ scaffolds with PLGA (P), MH-RA (M), ECM (E), ZnO-ALA (Z). The oxygen free radical scavenger EDV was incorporated to induce tubular regeneration. mEVs were engineered to serve regenerative activities with a combination of two EVs from SDF-1α overexpressed tonsil-derived mesenchymal stem cells (sEVs) and intermediate mesoderm (IM) cells during differentiation into kidney progenitor cells (dEVs). mEVs displayed beneficial effects on regeneration by facilitating migration and inducing differentiation of surrounding stem cells, and EDV improved kidney function by regulating the GDNF/RET pathway and their downstream genes. The promotion of MSC recruitment was confirmed with sEV particles number dependently, and the regulation of the GDNF/RET pathway by the effect of EDV and its enhanced effect by mEVs were elucidated using in vitro analysis. The regeneration of tubules was additionally demonstrated through the increased expression of aquaporin-1 (AQP-1) and cadherin-16 (CDH16) for proximal tubules, and calbindin and PAX2 for distal tubules in the renal defect model. With these, structural regeneration and functional recovery were achieved with kidney regeneration in the 5/6 nephrectomy mice model.Graphical abstract

Research on tire internal defect identification method based on deep learning

As an important part of automobile, the safety and durability of tire have attracted more and more attention. Tire defect detection is an important link to ensure tire quality, while traditional detection methods have problems such as low efficiency, high false detection rate and high labor intensity. Therefore, this study aims to develop an efficient and accurate tire defect identification and classification technique to improve the efficiency and accuracy of tire inspection. In this paper, based on YOLO (You Only Look Once) v5 algorithm, tire defect recognition and classification are studied. Firstly, the data sets containing various types of tire defects were collected and sorted out, and the data sets were preprocessed. Then, by constructing, training and optimizing the YOLOv5 tire defect recognition model, the fast and accurate recognition of tire defects was realized. Finally, the performance of the model was evaluated through experiments and compared with the existing methods. The experimental results show that the tire defect recognition and classification method based on YOLOv5 proposed in this study has high accuracy. Compared with traditional methods, this method has a significant improvement in detection speed and accuracy.

The response to single-gene duplication implicates translation as a key vulnerability in aneuploid yeast.

Aneuploidy produces myriad consequences in health and disease, yet models of the deleterious effects of chromosome amplification are still widely debated. To distinguish the molecular determinants of aneuploidy stress, we measured the effects of duplicating individual genes in cells with different chromosome duplications, in wild-type cells (SSD1+) and cells sensitized to aneuploidy by deletion of RNA-binding protein Ssd1 (ssd1Δ). We identified gene duplications that are nearly neutral in wild-type euploid cells but significantly deleterious in euploids lacking SSD1 or in SSD1+ aneuploid cells with different chromosome duplications. Several of the most deleterious genes are linked to translation. In contrast, duplication of other genes benefits multiple ssd1Δ aneuploids over controls, and this group is enriched for translational effectors. Furthermore, both wild-type and especially ssd1Δ aneuploids with different chromosome amplifications show increased sensitivity to translational inhibitor nourseothricin. We used comparative modeling of aneuploid growth defects, based on the cumulative fitness costs measured for single-gene duplication. Our results present a model in which the deleterious effects of aneuploidy emerge from an interaction between the cumulative burden of many amplified genes on a chromosome and a subset of duplicated genes that become toxic in that context. These findings provide a perspective on the dual impact of individual genes and overall genomic burden, offering new avenues for understanding aneuploidy and its cellular consequences.

Injectable calcium phosphate cement integrated with BMSCs-encapsulated microcapsules for bone tissue regeneration

Injectable calcium phosphate cement (CPC) offers significant benefits for the minimally invasive repair of irregular bone defects. However, the main limitations of CPC, including its deficiency in osteogenic properties and insufficient large porosity, require further investigation and resolution. In this study, alginate-chitosan-alginate (ACA) microcapsules were used to encapsulate and deliver rat bone mesenchymal stem cells (rBMSCs) into CPC paste, while a porous CPC scaffold was established to support cell growth. Our results demonstrated that the ACA cell microcapsules effectively protect the cells and facilitate their transport into the CPC paste, thereby enhancing cell viability post-implantation. Additionally, the ACA + CPC extracts were found to stimulate osteogenic differentiation of rBMSCs. Furthermore, results from a rat cranial parietal bone defect model showed that ACA microcapsules containing exogenous rBMSCs initially improved thein situosteogenic potential of CPC within bone defects, providing multiple sites for bone growth. Over time, the osteogenic potential of the exogenous cells diminishes, yet the pores created by the microcapsules persist in supporting ongoing bone formation by recruiting endogenous cells to the osteogenic sites. In conclusion, the utilization of ACA loaded stem cell microcapsules satisfactorily facilitate osteogenesis and degradation of CPC, making it a promising scaffold for bone defect transplantation.

Synchronized long-term delivery of growth hormone and insulin-like growth factor 1 through poly (lactic-co-glycolic acid) nanoparticles on polycaprolactone scaffolds for enhanced osteochondral regeneration

The regeneration of osteochondral defects is challenging due to the complex structure of the osteochondral unit. This study aimed to develop a biomimetic scaffold by loading growth hormone (GH) and insulin-like growth factor-1 (IGF-1) into poly (lactic-co-glycolic acid) (PLGA) nanoparticles and incorporating them into polycaprolactone (PCL) scaffolds to promote synchronized osteochondral regeneration. The nanoparticles were successfully immobilized onto PCL scaffolds pre-modified with polydopamine (PDA) to enhance cell adhesion and proliferation. The scaffolds exhibited a sustained release of GH and IGF-1 over 30 days. In vitro studies using rabbit adipose-derived stem cells (ADSCs) showed that the GH/IGF-1 nanoparticle-loaded scaffolds (PCL/PDA/M-PLGA) significantly promoted cell proliferation, chondrogenic differentiation, and osteogenic differentiation compared to control PCL/PDA scaffolds. In vivo experiments using a rabbit osteochondral defect model revealed that the PCL/PDA/M-PLGA scaffolds facilitated superior osteochondral regeneration, evidenced by increased subchondral bone formation and cartilage matrix deposition. Overall, this study demonstrates the potential of GH/IGF-1 nanoparticle-loaded PCL scaffolds for synchronized osteochondral regeneration and provides a promising strategy for treating osteochondral defects.

Enhancement of a one-step membrane technique for the treatment of large bone defects by pre-seeding the membrane with CD8 lymphocyte depleted bone marrow mononuclear cells in a rat femoral defect model.

The one-step membrane technique, using a human acellular dermal matrix (hADM), is an experimental method for treating large bone defects. This eliminates the need for the Masquelet membrane induction step, shortening the procedure while maintaining effectiveness. However, previous studies showed that colonizing hADM with bone marrow mononuclear cells (BMC) worsens healing, likely due to the presence of CD8+ lymphocytes, which negatively affect bone regeneration. This study aims to investigate whether the negative impact of BMC on bone healing in this technique is due to the CD8+ cell population. A 5 mm femoral defect was created in 25 male Sprague-Dawley rats, divided into three groups (G1-G3). BMC were isolated from syngenic donor rats, with CD8+ lymphocytes removed magnetically from the BMC fraction in one group. The defects were filled with bone chips and wrapped with differently treated hADM: G1 received native hADM, G2 received hADM+BMC, and G3 received hADM+BMC-CD8. After 8 weeks, the femurs were evaluated through radiological, biomechanical, and histological examinations. Bone defects and bone mineral density (BMD) were significantly improved in G3 (hADM+BMC-CD8) compared to G2 (hADM+BMC). Bone volume, bone formation, and median bending stiffness were higher in G3. Immunohistological analysis showed a significant decrease in CD8 cell count in G3, with a lower percentage of IFNγ-producing cells compared to G2. Depleting CD8+ cells from BMC before colonizing hADM significantly improved bone healing, likely due to changes in the local mediator environment. This suggests that preoperative colonization with CD8+-depleted BMC could enhance the one-step membrane technique.

Synthetic Periodontal Guided Tissue Regeneration Membrane with Self-Assembling Biphasic Structure and Temperature-Sensitive Shape Maintenance.

Periodontal disease poses significant challenges to the long-term stability of oral health by destroying the supporting structures of teeth. Guided tissue regeneration techniques, particularly barrier membranes, enable local regeneration by providing an isolated, protected compartment for osseous wound healing while excluding epithelial tissue. Here, this study reports on a thermosensitive periodontal membrane (TSPM) technology designed to overcome the mechanical limitations of current membranes through a semi-interpenetrating network of high molecular weight poly(L-lactic acid) (PLLA) and in situ-polymerized mesh of poly(ε-caprolactone)diacrylate (PCL-DA), and poly lactide-co-glycolide diacrylate (PLGA-DA). An optimized composition allows facile reshaping at greater than 52 °C and rigid shape maintenance at physiological temperature. Its unique bilayer morphology is achieved through self-assembly and thermally-induced phase separation, resulting in distinct yet continuous smooth and nanofibrous compartments adequate for epithelial occlusion and regeneration. Incorporating PLGA-DA enhances the membrane's hydrophilicity and degradation properties, facilitating a more rapid and controlled degradation and therapeutic delivery. This study demonstrates its ability to promote local regeneration by serving as a barrier membrane and simultaneously as a scaffolding matrix in a rat orthotopic periodontal defect model. The TSPM outperformed a clinically available material (Epi-Guide) to facilitate robust alveolar bone and periodontal ligament regeneration at 4 and 8 weeks.