Femoral Defects Research Articles

Bone Morphogenetic Protein 7-Loaded Gelatin Methacrylate/Oxidized Sodium Alginate/Nano-Hydroxyapatite Composite Hydrogel for Bone Tissue Engineering.

Bone tissue engineering (BTE) is a promising alternative to autologous bone grafting for the clinical treatment of bone defects, and inorganic/organic composite hydrogels as BTE scaffolds are a hot spot in current research. The construction of nano-hydroxyapatite/gelatin methacrylate/oxidized sodium alginate (nHAP/GelMA/OSA), abbreviated as HGO, composite hydrogels loaded with bone morphogenetic protein 7 (BMP7) will provide a suitable 3D microenvironment to promote cell aggregation, proliferation, and differentiation, thus facilitating bone repair and regeneration. Dually-crosslinked hydrogels were fabricated by combining GelMA and OSA, while HGO hydrogels were formulated by incorporating varying amounts of nHAP. The hydrogels were physically and chemically characterized followed by the assessment of their biocompatibility. BMP7-HGO (BHGO) hydrogels were fabricated by incorporating suitable concentrations of BMP7 into HGO hydrogels. The osteogenic potential of BHGO hydrogels was then validated through in vitro experiments and using rat femoral defect models. The addition of nHAP significantly improved the physical properties of the hydrogel, and the composite hydrogel with 10% nHAP demonstrated the best overall performance among all groups. The selected concentration of HGO hydrogel served as a carrier for BMP7 loading and was evaluated for its osteogenic potential both in vivo and in vitro. The BHGO hydrogel demonstrated superior in vitro osteogenic induction and in vivo potential for repairing bone tissue compared to the outcomes observed in the blank control, BMP7, and HGO groups. Using hydrogel containing 10% HGO appears promising for bone tissue engineering scaffolds, especially when loaded with BMP7 to boost its osteogenic potential. However, further investigation is needed to optimize the GelMA, OSA, and nHAP ratios, along with the BMP7 concentration, to maximize the osteogenic potential.

Smurf1-targeting microRNA-136-5p-modified bone marrow mesenchymal stem cells combined with 3D-printed β-tricalcium phosphate scaffolds strengthen osteogenic activity and alleviate bone defects.

Suitable biomaterials with seed cells have promising potential to repair bone defects. However, bone marrow mesenchymal stem cells (BMSCs), one of the most common seed cells used in tissue engineering, cannot differentiate efficiently and accurately into functional osteoblasts. In view of this, a new tissue engineering technique combined with BMSCs and scaffolds is a major task for bone defect repair. Lentiviruses interfering with miR-136-5p or Smurf1 expression were transfected into BMSCs. The effects of miR-136-5p or Smurf1 on the osteogenic differentiation (OD) of BMSCs were evaluated by measuring alkaline phosphatase activity and calcium deposition. Then, the targeting relationship between miR-136-5p and Smurf1 was verified by bioinformatics website analysis and dual luciferase reporter assay. Then, a rabbit femoral condyle bone defect model was established. miR-136-5p/BMSCs/β-TCP scaffold was implanted into the defect, and the repair of the bone defect was detected by Micro-CT and HE staining. Elevating miR-136-5p-3p or suppressing Smurf1 could stimulate OD of BMSCs. miR-136-5p negatively regulated Smurf1 expression. Overexpressing Smurf1 reduced the promoting effect of miR-136-5p on the OD of BMSCs. miR-136-5p/BMSCs/β-TCP could strengthen bone density in the defected area and accelerate bone repair. SmurF1-targeting miR-136-5p-modified BMSCs combined with 3D-printed β-TCP scaffolds can strengthen osteogenic activity and alleviate bone defects.

In vivo trial of bioresorbable mesh cages contained bone graft granules in rabbit femoral bone defects

Bone graft granules implanted in bone defects come into physical contact with the host bone and form interconnected porous structure. However, there exists an accidental displacement of granules to unintended locations and leakage of granules from bone defects. Although covering the defect with a barrier membrane prevents granule emanation, this procedure is troublesome. To resolve these problems, we fabricated bioresorbable mesh cages (BRMc) in this study. Bone graft granules composed of carbonate apatite alone (Gr) and bioresorbable mesh cages (BRMc/Gr) introduced the bone graft granules and were implanted into the bone defect in the rabbit femur. Micro-computed tomography and histological analysis were conducted at 4 and 12 weeks after implantation. Osteoprogenitors in the bloodstream from the host bone passed through the pores of BRMc, penetrated the porous structure of graft granules, and might interact with individual granules. Then bone remodeling could progress actively and new bone was formed. The new bone formation was similar to the host bone at 12 weeks and there were minimal signs of local tissue inflammation. BRMc/Gr could reduce the risk of unwanted new bone formation occurring due to loss of granules from the bone defects compared with Gr because BRMc enclosed granules and prevent granules leakage from bone defects and BRMc could not induce unfavorable effects to forme new bone. Additionally, BRMc/Gr could keep granules assembled in one place, avoid displacement of granules to unintended locations, and carry easily. These results demonstrated that BRMc/Gr was effective in bone regeneration and improved clinical handling.

Research on Characterization and Biocompatibility of 3D Printed Ti-6Al-4V Pelvic Prosthesis

The treatment of bone defects caused by fractures or bone tissue lesions has always been a difficult problem in the field of orthopedics. Implantation of high-performance titanium alloy prosthesis is an effective method to treat bone defects. 3D printing technology can produce low-modulus titanium alloy implants with porous structures, providing a better solution to the above problems. This technology is convenient to design and has a huge advantage in making orthopedic implants. The article used electron beam melting in 3D printing technology to create two samples of Ti-6Al-4V prosthesis, including solid structural pelvic prosthesis and porous structural pelvic prosthesis. The mechanical properties of the prosthesis showed that the yield and tensile strengths of the rod tensile specimen were 894 MPa and 956 MPa, respectively, and the compressive modulus and compressive strength of the porous pelvic prosthesis were 55 GPa and 65.2 MPa, respectively. The results of the L929 cytotoxicity assay and the MC3T3-E1 cell adhesion assay demonstrated good biocompatibility of the prosthetic samples. New Zealand white rabbits were used to prepare the femoral joint cavity defect models and two pelvic prostheses were implanted. A microscopic CT scan 4 weeks after implantation showed that the bone defect caused by the drill had healed and that the porous structure of the pelvic prosthesis formed a new trabecular structure within the hole. In conclusion, the 3D printed Ti-6Al-4V pelvic prosthesis has excellent mechanical properties, biocompatibility, and the ability to promote new bone growth.

In Vivo feature of the regenerative potential of chitosan and alginate based osteoplastic composites doped with calcium phosphates, zinc ions, and vitamin D2

PurposeIn vivo comparison of the regenerative potential of two calcium phosphate-biopolymer osteoplastic composites: а) based on alginate (Alg) and hydroxyapatite (HA) – Alg/HA/CS/Zn/D2, b) based on chitosan (CS) and brushite (DCPD) – CS/DCPD/D2. Materials and methods36 white male laboratory rats aged six months were used. A defect to the bone marrow canal in the middle of the femur diaphysis was made with a dental bur of 2 mm. The bone defect healed under the blood clot (control) in the different animal groups and was filled with Alg/HA/CS/Zn/D2 and CS/DCPD/D2. The regeneration of the bone defect was studied on the 30th, 90th, and 140th days by computer tomography (CT). ResultsOn the 30th day, all groups' implantation site optical density (OD) was significantly lower than that of the adjacent maternal bone (MB). Intensity of bone formation for Alg/HA/CS/Zn/D2 exceeds CS/DCPD/D2. On the 90th day, the bone trauma site OD with Alg/HA/CS/Zn/D2 (1725.4 ± 86 HU) and CS/DCPD/D2 (1484.9 ± 69 HU) exceeded the OD of the control (942.5 ± 55 HU). On the 140th day, the OD of Alg/HA/CS/Zn/D2 and CS/DCPD/D2 implantation sites was higher than Control and MB OD. Visually, the area of the past injury with the Alg/HA/CS/Zn/D2 could be detected only by the presence of an endosteal bone callus and in the case of CS/DCPD/D2 - by the shadow of the remaining biomaterial in the bone marrow canal. ConclusionsAccording to CT data, Alg/HA/CS/Zn/D2 and CS/DCPD/D2 contribute to the complete healing of the femoral diaphysis defect in 140 days, but the regenerative potential of Alg/HA/CS/Zn/D2 from 30 days to 140 days is higher than CS/DCPD/D2 biomaterial.

Selective ion doping core-shell bioceramic fiber-derived granules readily tuning biodegradation and initiating osteoporotic bone defect repair

Osteoporotic bone defect repair is one of the challenges in orthopedics because there are no preferable biomaterials to readily initiate new bone regeneration in critical-size pathological bone damage. Our previous studies revealed that core–shell Ca-phosphate/silicate microspheres can tune time-evolving biodegradation, which is beneficial for modulating bone repair. Herein, we expanded this strategy to develop core–shell-type 5 % Sr- and 8 % Zn-doped wollastonite fiber-derived granules with different porosities (0 %, 10 %, 20 %) in the shell layer. Physicochemical analyses indicated that granules with higher porosity in the shell layer exhibited more appreciable Sr and Zn ion release and biodissolution in vitro. Osteoporotic femoral bony defects in rabbits were used to verify the osteogenic efficacy of the core–shell granules. The granules with 10 % porosity could initiate more osteogenesis within 6 weeks, and the new bone tissue could grow into the defect region, while the new bone tissue only migrated into the periphery pores under the other granule conditions. Histological evaluation also revealed appreciable new bone ingrowth in the granules with 10 % porosity, whereas the other implant groups had limited new bone tissue. These findings demonstrate that bone repair initiation can be enhanced by finely designed local porosity in specific components of core–shell bioceramic fiber-tailoring granules to control bioactive ion release and osteo-stimulation in vivo; moreover, such bioceramic fabrication is promising for developing osteo-stimulative implants to resolve clinically challenging bone defect repair.

EMERGENCY LAPAROSCOPIC TRANSABDOMINAL PREPERITONEAL (TAPP) HERNIOPLASTY FOR GARANGEOT'S HERNIA: A CASE REPORT

Abstract Aims This video presentation aims to demonstrate the successful management of a rare and challenging case of Garangeot's hernia through Emergency Laparoscopic Transabdominal Preperitoneal (TAPP) Hernioplasty. The primary objectives include highlighting the surgical technique, intraoperative findings, and postoperative outcomes in the context of this uncommon hernia presentation. Materials and Methods An 84-year-old female presented to the emergency department with signs of femoral hernia incarceration. Upon exploration, a Garangeot's hernia, characterized by the presence of the appendix within a femoral hernia sac, was identified. In light of the emergency and the patient's deteriorating condition, an Emergency Laparoscopic TAPP Hernioplasty was performed. The procedure involved meticulous dissection of the hernia sac, reduction of the herniated appendix and appendectomy, and subsequent mesh reinforcement of the femoral defect. Results The video illustrates the step-by-step approach to Emergency Laparoscopic TAPP Hernioplasty in the context of Garangeot's hernia. Intraoperative findings, including the condition of the herniated appendix and associated anatomical structures, are presented. Postoperative outcomes, including recovery, complications, and follow-up observations, are discussed to provide a comprehensive understanding of the case. Conclusions Emergency Laparoscopic TAPP Hernioplasty emerges as a viable and effective intervention for Garangeot's hernia, offering advantages such as reduced morbidity, quicker recovery, and minimal surgical trauma. This video contributes valuable insights into the management of this rare hernia presentation, emphasizing the role of minimally invasive techniques in achieving successful outcomes.

Synergistic effect of umbilical cord extracellular vesicles and rhBMP-2 to enhance the regeneration of a metaphyseal femoral defect in osteoporotic rats

BackgroundThe aim of this study was to evaluate potential synergistic effects of a single, local application of human umbilical cord MSC-derived sEVs in combination with a low dose of recombinant human rhBMP-2 to promote the regeneration of a metaphyseal femoral defect in an osteoporotic rat model.Methods6 weeks after induction of osteoporosis by bilateral ventral ovariectomy and administration of a special diet, a total of 64 rats underwent a distal femoral metaphyseal osteotomy using a manual Gigli wire saw. Defects were stabilized with an adapted Y-shaped mini-locking plate and were subsequently treated with alginate only, or alginate loaded with hUC-MSC-sEVs (2 × 109), rhBMP-2 (1.5 µg), or a combination of sEVs and rhBMP-2 (n = 16 for each group). 6 weeks post-surgery, femora were evaluated by µCT, descriptive histology, and biomechanical testing.ResultsNative radiographs and µCT analysis confirmed superior bony union with callus formation after treatment with hUC-MSC-sEVs in combination with a low dose of rhBMP-2. This finding was further substantiated by histology, showing robust defect consolidation 6 weeks after treatment. Torsion testing of the explanted femora revealed increased stiffness after application of both, rhBMP-2 alone, or in combination with sEVs, whereas torque was only significantly increased after treatment with rhBMP-2 together with sEVs.ConclusionThe present study demonstrates that the co-application of hUC-MSC-sEVs can improve the efficacy of rhBMP-2 to promote the regeneration of osteoporotic bone defects.

Effect of M2-macrophage treated lymphatic endothelial cells on angiogenesis that promoted osteointegration

Early vascularization plays an essential role during the whole process in bone regeneration because of the function of secreting cytokines, transporting nutrients and metabolic wastes. As the preliminary basis of bone repair, angiogenesis is regulated by immune cells represented by macrophages to a great extent. However, with the discovery of the endolymphatic circulation system inside bone tissue, the role of vascularization became complicated and confusing. Herein, we developed a macrophage/lymphatic endothelial cells (LECs)/human umbilical vein endothelial cells (HUVECs) co-culture system to evaluate the effect of macrophage treated lymphatic endothelial cells on angiogenesis in vitro and in vivo. In this study, we collected the medium from macrophage (CM) for LECs culture. We found that CM2 could promote the expression of LECs markers and migration ability, which indicated the enhanced lymphogenesis. In addition, the medium from LECs was collected for culturing HUVECs. The CM2-treated LECs showed superior angiogenesis property including the migration capacity and expression of angiogenetic markers, which suggested the superior vascularization. Rat femoral condyle defect model was applied to confirm the hypothesis in vivo. Generally, M2-macrophage treated LECs showed prominent angiogenetic potential coupling with osteogenesis.

Activating Macrophage Continual Efferocytosis via Microenvironment Biomimetic Short Fibers for Reversing Inflammation in Bone Repair.

Efferocytosis-mediated inflammatory reversal plays a crucial role in bone repairing process. However, in refractory bone defects, the macrophage continual efferocytosis may be suppressed due to the disrupted microenvironment homeostasis, particularly the loss of apoptotic signals and overactivation of intracellular oxidative stress. In this study, a polydopamine-coated short fiber matrix containing biomimetic "apoptotic signals" to reconstruct the microenvironment and reactivate macrophage continual efferocytosis for inflammatory reversal and bone defect repair is presented. The "apoptotic signals" (AM/CeO2) are prepared using CeO2 nanoenzymes with apoptotic neutrophil membrane coating for macrophage recognition and oxidative stress regulation. Additionally, a short fiber "biomimetic matrix" is utilized for loading AM/CeO2 signals via abundant adhesion sites involving π-π stacking and hydrogen bonding interactions. Ultimately, the implantable apoptosis-mimetic nanoenzyme/short-fiber matrixes (PFS@AM/CeO2), integrating apoptotic signals and biomimetic matrixes, are constructed to facilitate inflammatory reversal and reestablish the pro-efferocytosis microenvironment. In vitro and in vivo data indicate that the microenvironment biomimetic short fibers can activate macrophage continual efferocytosis, leading to the suppression of overactivated inflammation. The enhanced repair of rat femoral defect further demonstrates the osteogenic potential of the pro-efferocytosis strategy. It is believed that the regulation of macrophage efferocytosis through microenvironment biomimetic materials can provide a new perspective for tissue repair.

Bone Regenerative Effect of Injectable Hypoxia Preconditioned Serum-Fibrin (HPS-F) in an Ex Vivo Bone Defect Model.

Biofunctionalized hydrogels are widely used in tissue engineering for bone repair. This study examines the bone regenerative effect of the blood-derived growth factor preparation of Hypoxia Preconditioned Serum (HPS) and its fibrin-hydrogel formulation (HPS-F) on drilled defects in embryonic day 19 chick femurs. Measurements of bone-related growth factors in HPS reveal significant elevations of Osteopontin, Osteoprotegerin, and soluble-RANKL compared with normal serum (NS) but no detection of BMP-2/7 or Osteocalcin. Growth factor releases from HPS-F are measurable for at least 7 days. Culturing drilled femurs organotypically on a liquid/gas interface with HPS media supplementation for 10 days demonstrates a 34.6% increase in bone volume and a 52.02% increase in bone mineral density (BMD) within the defect area, which are significantly higher than NS and a basal-media-control, as determined by microcomputed tomography. HPS-F-injected femur defects implanted on a chorioallantoic membrane (CAM) for 7 days exhibit an increase in bone mass of 123.5% and an increase in BMD of 215.2%, which are significantly higher than normal-serum-fibrin (NS-F) and no treatment. Histology reveals calcification, proteoglycan, and collagen fiber deposition in the defect area of HPS-F-treated femurs. Therefore, HPS-F may offer a promising and accessible therapeutic approach to accelerating bone regeneration by a single injection into the bone defect site.

Obturator to Femoral Nerve Transfer: 2-Dimensional Operative Video.

Injury to the femoral nerve can cause femoral nerve palsy,1 resulting in severe ambulation difficulties and loss of sensory function in the anteromedial thigh and medial calf.2,3 Treatment options focus on nerve repair by direct coaptation, nerve grafting, or nerve transfer.3 If the proximal nerve stump is inaccessible, the location of nerve injury is at a distance from the site of muscle innervation, and/or there is a large nerve gap, nerve transfer may be a promising alternative treatment option.4-6 Nerve transfer uses only one coaptation site and allows for a faster recovery time due to a shorter nerve regeneration distance.2,3 A 32-year-old woman presented with persistent and severe proximal right lower extremity weakness after a right retroperitoneal femoral nerve schwannoma resection at an outside institution. After surgery, she reported that she could not flex her right hip or extend her right knee. MRI demonstrated a right femoral nerve gap defect (7.5 cm) at the schwannoma resection site. A right obturator to femoral nerve transfer was performed (see Video). 1.5-year follow-up visit showed that she had begun to have evidence of active recruitment of the right quadriceps muscle and started walking without a knee brace. 2.5-year follow-up visit showed improving strength (4-) in her right quadriceps muscle, independent walking for longer distances, and participation in sporting activities. The patient consented to the procedure, and the patients and any identifiable individuals consented to publication of his/her image. Institutional Review Board approval was not required for this single case observational surgical video.

Productizing Nano-Bioactive Glass-Based Bilayer Scaffolds: A Graft for Reconstruction of Mandibular and Femoral Bone Defects.

This investigation aimed to construct a bilayer scaffold integrating alginate and gelatin with nanobioactive glass (BG), recognized for their efficacy in tissue regeneration and drug delivery. Scaffolds, namely, alginate/gelatin (AG), alginate-/actonel gelatin (AGD), alginate actenol/gelatin-45S5 BG (4AGD), and alginate-actonel/gelatin-59S BG (5AGD), were assembled using a cost-effective freeze-drying method, followed by detailed structural investigation via powder X-ray diffraction as well as morphological characterization using field emission scanning electron microscopy (FESEM). FESEM revealed a honeycomb-like morphology with distinct pore sizes for nutrient, oxygen, and drug transport. The scaffolds evidently exhibited hemocompatibility, high porosity, good swelling capacity, and biodegradability. In vitro studies demonstrated sustained drug release, particularly for scaffolds containing actonel. In vivo tests showed that the bilayer scaffold promoted new bone formation, surpassing the control group in bone area increase. The interaction of the scaffold with collagen and released ions improved the osteoblastic function and bone volume fraction. The findings suggest that this bilayer scaffold could be beneficial for treating critical-sized bone defects, especially in the mandibular and femoral regions.

An adaptive biodegradable zinc alloy with bidirectional regulation of bone homeostasis for treating fractures and aged bone defects

Healing of fractures or bone defects is significantly hindered by overactivated osteoclasts and inhibited osteogenesis in patients with abnormal bone metabolism. Current clinical approaches using titanium alloys or stainless steel provide mechanical support but have no biological effects on bone regeneration. Therefore, designing and fabricating degradable metal materials with sufficient mechanical strength and bidirectional regulation of both osteoblasts and osteoclasts is a substantial challenge. Here, this study first reported an adaptive biodegradable Zn-0.8 Mg alloy with bidirectional regulation of bone homeostasis, which promotes osteogenic differentiation by activating the Pi3k/Akt pathway and inhibits osteoclast differentiation by inhibiting the GRB2/ERK pathway. The anti-osteolytic ability of the Zn-0.8 Mg alloy was verified in a mouse calvarial osteolysis model and its suitability for internal fracture fixation with high-strength screws was confirmed in the rabbit femoral condyle fracture model. Furthermore, in an aged postmenopausal rat femoral condyle defect model, 3D printed Zn-0.8 Mg scaffolds promoted excellent bone regeneration through adaptive structures with good mechanical properties and bidirectionally regulated bone metabolism, enabling personalized bone defect repair. These findings demonstrate the substantial potential of the Zn-0.8 Mg alloy for treating fractures or bone defects in patients with aberrant bone metabolism.

Advancing Osteoporotic Bone Regeneration Through Tailored Tea Polyphenols Functionalized Micro‐/Nano‐ Hydroxyapatite Bioceramics

AbstractEfforts to develop advanced bone substitutes for effective bone regeneration in substantial defects have led to the fabrication of tissue‐engineered scaffolds. These scaffolds, featuring hierarchical structures, specific chemical compositions, and functional qualities, are essential in mimicking native bone tissue. Inspired by the biomineralization process, hydrothermal treatment is used to synthesize micro‐/nano‐hydroxyapatite bioceramics functionalized with tea polyphenols (TP‐nwHA), closely resembling the structure of bone‐like apatite induced by hydroxyapatite bioceramics in vivo. The in vitro results demonstrate TP‐nwHA's superior biocompatibility, enhancing cell proliferation and adhesion. Furthermore, TP‐nwHA scaffolds significantly influence mesenchymal stem cells, promoting osteogenic differentiation while inhibiting osteoclastogenic differentiation. The upregulation of osteogenic proteins BMP2 and ITGB1, along with the downregulation of osteoclastic proteins FGF21 and IGFBP1, demonstrate the synergistic effect of the biomimetic structure and polyphenols on the activation of the MAPK signaling pathway. In vivo, TP‐nwHA showe early angiogenic capabilities, leading to improved bone regeneration in critical‐size femoral bone defects in osteoporotic rats. Histological staining confirms the complete bridging of defects with new bone tissue in the TP‐nwHA group, and nanoindentation tests indicate the formation of mature mineralized bone tissue. Collectively, these findings suggest a novel strategy for fabricating bone‐mimicking constructs with potential applications in disease modeling.

A rabbit osteochondral defect (OCD) model for evaluation of tissue engineered implants on their biosafety and efficacy in osteochondral repair.

Osteochondral defect (OCD) is a common but challenging condition in orthopaedics that imposes huge socioeconomic burdens in our aging society. It is imperative to accelerate the R&D of regenerative scaffolds using osteochondral tissue engineering concepts. Yet, all innovative implant-based treatments require animal testing models to verify their feasibility, biosafety, and efficacy before proceeding to human trials. Rabbit models offer a more clinically relevant platform for studying OCD repair than smaller rodents, while being more cost-effective than large animal models. The core-decompression drilling technique to produce full-thickness distal medial femoral condyle defects in rabbits can mimic one of the trauma-relevant OCD models. This model is commonly used to evaluate the implant's biosafety and efficacy of osteochondral dual-lineage regeneration. In this article, we initially indicate the methodology and describe a minimally-invasive surgical protocol in a step-wise manner to generate a standard and reproducible rabbit OCD for scaffold implantation. Besides, we provide a detailed procedure for sample collection, processing, and evaluation by a series of subsequent standardized biochemical, radiological, biomechanical, and histological assessments. In conclusion, the well-established, easy-handling, reproducible, and reliable rabbit OCD model will play a pivotal role in translational research of osteochondral tissue engineering.

A sponge-like nanofiber melatonin-loaded scaffold accelerates vascularized bone regeneration via improving mitochondrial energy metabolism

Electrospun nanofibers have been widely employed in bone tissue engineering for their ability to mimic the micro to nanometer scale network of the native bone extracellular matrix. However, the dense fibrous structure and limited mechanical support of these nanofibers pose challenges for the treatment of critical size bone defects. In this study, we propose a facile approach for creating a three-dimensional scaffold using interconnected electrospun nanofibers containing melatonin (Scaffold@MT). The hypothesis posited that the sponge-like Scaffold@MT could potentially enhance bone regeneration and angiogenesis by modulating mitochondrial energy metabolism. Melatonin-loaded gelatin and poly-lactic-acid nanofibers were fabricated using electrospinning, then fragmented into shorter fibers. The sponge-like Scaffold@MT was created through a process involving homogenization, low-temperature lyophilization, and chemical cross-linking, while maintaining the microstructure of the continuous nanofibers. The incorporation of short nanofibers led to a low release of melatonin and increased Young's modulus of the scaffold. Scaffold@MT demonstrated positive biocompatibility by promoting a 14.2 % increase in cell proliferation. In comparison to the control group, Scaffold@MT significantly enhanced matrix mineralization by 3.2-fold and upregulated the gene expression of osteoblast-specific markers, thereby facilitating osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs). Significantly, Scaffold@MT led to a marked enhancement in the mitochondrial energy function of BMMSCs, evidenced by elevated adenosine triphosphate (ATP) production, mitochondrial membrane potential, and protein expression of respiratory chain factors. Furthermore, Scaffold@MT promoted the migration of human umbilical vein endothelial cells (HUVECs) and increased tube formation by 1.3 times compared to the control group, accompanied by an increase in vascular endothelial growth factor (VEGFA) expression. The results of in vivo experiments indicate that the implantation of Scaffold@MT significantly improved vascularized bone regeneration in a distal femur defect in rats. Micro-computed tomography analysis conducted 8 weeks post-surgery revealed that Scaffold@MT led to optimal development of new bone microarchitecture. Histological and immunohistochemical analyses demonstrated that Scaffold@MT facilitated bone matrix deposition and new blood vessel formation at the defect site. Overall, the utilization of melatonin-loaded nanofiber sponges exhibits significant promise as a scaffold that promotes bone growth and angiogenesis, making it a viable option for the repair of critical-sized bone defects.

Study on degradation behavior of porous magnesium alloy scaffold loaded with rhBMP-2 and repair of bone defects

Magnesium (Mg) is abundant in humans. Studies have shown that Mg2+ significantly affects physiological processes such as osteogenesis, osteoblast adhesion and motility, immunomodulation, and angiogenesis. Mg-based alloy porous scaffolds have attracted increasing attention because of their degradability and mechanical properties. Hence, wire-cut EDM was used to fabricate porous scaffolds. In addition, fluoride treatment afforded an MgF2 coating, and racemic polylactic acid PDLLA was used as the carrier of rhBMP-2, which was evenly coated on the surface of the passivated porous alloy scaffold to slowly release growth factors and slow down the degradation rate. The rat femoral condyle defect model experiment was performed to study the in vivo bone regeneration capacity of porous scaffolds and compare the differences in the healing effect with or without rhBMP-2. The enhanced corrosion resistance of the porous scaffold was confirmed through in vitro immersion experiments. Micro-CT implied that porous scaffold with rhBMP-2 induced new bone formation and the new bone formation along the pores, as well as the histological examination in vivo. In summary, the porous scaffold promotes bone formation and has great potential for clinical translation.

Enhanced Bone Healing in Critical-Sized Rabbit Femoral Defects: Impact of Helical and Alternate Scaffold Architectures.

This study investigates the effect of scaffold architecture on bone regeneration, focusing on 3D-printed polylactic acid-bioceramic calcium phosphate (PLA-bioCaP) composite scaffolds in rabbit femoral condyle critical defects. We explored two distinct scaffold designs to assess their influence on bone healing and scaffold performance. Structures with alternate (0°/90°) and helical (0°/45°/90°/135°/180°) laydown patterns were manufactured with a 3D printer using a fused deposition modeling technique. The scaffolds were meticulously characterized for pore size, strut thickness, porosity, pore accessibility, and mechanical properties. The in vivo efficacy of these scaffolds was evaluated using a femoral condyle critical defect model in eight skeletally mature New Zealand White rabbits. Then, the results were analyzed micro-tomographically, histologically, and histomorphometrically. Our findings indicate that both scaffold architectures are biocompatible and support bone formation. The helical scaffolds, characterized by larger pore sizes and higher porosity, demonstrated significantly greater bone regeneration than the alternate structures. However, their lower mechanical strength presented limitations for use in load-bearing sites.

Cytokine Receptor-like Factor 1 (CRLF1) and Its Role in Osteochondral Repair.

Since cytokine receptor-like factor 1 (CRLF1) has been implicated in tissue regeneration, we hypothesized that CRLF1 released by mesenchymal stem cells can promote the repair of osteochondral defects. The degree of a femoral osteochondral defect repair in rabbits after intra-articular injections of bone marrow-derived mesenchymal stem cells (BMSCs) that were transduced with empty adeno-associated virus (AAV) or AAV containing CRLF1 was determined by morphological, histological, and micro computer tomography (CT) analyses. The effects of CRLF1 on chondrogenic differentiation of BMSCs or catabolic events of interleukin-1beta-treated chondrocyte cell line TC28a2 were determined by alcian blue staining, gene expression levels of cartilage and catabolic marker genes using real-time PCR analysis, and immunoblot analysis of Smad2/3 and STAT3 signaling. Intra-articular injections of BMSCs overexpressing CRLF1 markedly improved repair of a rabbit femoral osteochondral defect. Overexpression of CRLF1 in BMSCs resulted in the release of a homodimeric CRLF1 complex that stimulated chondrogenic differentiation of BMSCs via enhancing Smad2/3 signaling, whereas the suppression of CRLF1 expression inhibited chondrogenic differentiation. In addition, CRLF1 inhibited catabolic events in TC28a2 cells cultured in an inflammatory environment, while a heterodimeric complex of CRLF1 and cardiotrophin-like Cytokine (CLC) stimulated catabolic events via STAT3 activation. A homodimeric CRLF1 complex released by BMSCs enhanced the repair of osteochondral defects via the inhibition of catabolic events in chondrocytes and the stimulation of chondrogenic differentiation of precursor cells.