Promote Bone Growth Research Articles

Incorporating Hydrogel (with Low Polymeric Content) into 3D-Printed PLGA Scaffolds for Local and Sustained Release of BMP2 in Repairing Large Segmental Bone Defects.

Treating large bone defects remains a considerable challenge for clinicians: bone repair requires scaffolds with mechanical properties and bioactivities. Herein, based on crosslinking o-phthalaldehyde (OPA) with amine groups, 4-arm polyethylene glycol (4armPEG)-OPA/Gelatin hydrogel loaded with bone morphogenetic protein 2 (BMP2) is prepared and a three dimensional (3D)-printed poly (lactic-co-glycolic acid) (PLGA) porous scaffold is filled with the hydrogel solution. The composite scaffold, with a compression modulus of 0.68 ±0.097GPa similar to the cancellous bone, has a porosity of 56.67 ± 4.72% and a pore size of about 380µm, promoting bone growth. The hydrogel forms a porous network at low concentrations, aiding protein release and cell migration. The hydrogel degrades in approximately three weeks, and the scaffold takes five months, matching bone repair timelines. BMP2 release experiment shows a sustained BMP2 release with a 72.4 ± 0.53% release ratio. The ALP activity test and alizarin red staining shows effective osteogenic promotion, while RT-PCR confirms BMP2@Gel enhanced COL-1 and OPN expression. Animal experiments further validate the composite scaffold's bone repair efficacy. This study demonstrates the effectiveness of the hydrogel in releasing BMP2 and the mechanical support of the 3D-printed PLGA porous scaffold, providing a new treatment for bone defects.

Structural design and biomechanical analysis of a combined titanium and polyetheretherketone cage based on PE-PLIF fusion.

In lumbar spinal fusion, the titanium cage tends to cause stress shielding due to their high elastic modulus, which can lead to degenerative lesions in adjacent spinal segments. Furthermore, polyetheretherketone (PEEK) cages have certain material characteristics that do not promote bone ingrowth and fusion stability. In this study, a new cage was designed, and its biomechanical performance in percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) was analyzed using the finite element (FE) method. A complete model of the L4-L5 lumbar spine was established, and static and harmonic vibration FE analysis models were developed based on it. The biomechanical properties of titanium, PEEK, and combined cage in PE-PLIF fusion were compared. The strain capacity of the combined fusion increased by 9.5% when compared to the titanium fusion. The surgical model under the combined fusion reduces the L5 endplate stress by 12% in the forward flexion condition and the fusion stress by 17% in the vibration condition compared to the model supported by the titanium fusion, and the differences in screw stress and mobility among the three models are not significant in multiple conditions. Consequently, the combined cage demonstrates a certain reduction in the stress-shielding effect when compared to the titanium cage; it has better fusion effect and provides theoretical support and guidance for the design of the clinical fusion cage.

Evaluation of the immune response of peripheral blood mononuclear cells cultured on Ti6Al4V-ELI polished or etched surfaces.

While titanium and its alloys exhibit excellent biocompatibility and corrosion resistance, their polished surfaces can hinder fast and effective osseointegration and other biological processes, such as angiogenesis, due to their inert and hydrophobic properties. Despite being commonly used for orthopedic implants, research focuses on developing surface treatments to improve osseointegration, promoting cell adhesion and proliferation, as well as increasing protein adsorption capacity. This study explores a chemical treatment intended for titanium-based implants that enhances tissue integration without compromising the mechanical properties of the Ti6Al4V substrate. However, recognizing that inflammation contributes to nearly half of early implant failures, we assessed the impact of this treatment on T-cell viability, cytokine production, and phenotype. Ti6Al4V with extra low interstitial (ELI) content discs were treated with hydrofluoric acid followed by a controlled oxidation step in hydrogen peroxide that creates a complex surface topography with micro- and nano-texture and modifies the chemistry of the surface oxide layer. The acid etched surface contains an abundance of hydroxyl groups, crucial for promoting bone growth and apatite precipitation, while also enabling further functionalization with biomolecules. While cell viability remained high in both groups, untreated discs triggered an increase in Th2 cells and a decrease of the Th17 subset. Furthermore, peripheral blood mononuclear cells exposed to untreated discs displayed a rise in various pro-inflammatory and anti-inflammatory cytokines compared to the control and treated groups. Conversely, the treated discs showed a similar profile to the control, both in terms of immune cell subset frequencies and cytokine secretion. The dysregulation of the cytokine profile upon contact with untreated Ti6Al4V-ELI discs, namely upregulation of IL-2 could be responsible for the decrease in Th17 frequency, and thus might contribute to implant-associated bacterial infection. Interestingly, the chemical treatment restores the immune response to levels comparable to the control condition, suggesting the treatment's potential to mitigate inflammation by enhancing biocompatibility.

Novel 3D printed bioactive SiC orthopedic screw promotes bone growth associated activities by macrophages, neurons, and osteoblasts.

Ceramic additive manufacturing currently relies on binders or high-energy lasers, each with limitations affecting final product quality and suitability for medical applications. To address these challenges, our laboratory has devised a surface activation technique for ceramic particles that eliminates the necessity for polymer binders or high-energy lasers in ceramic additive manufacturing. We utilized this method to 3D print bioactive SiC orthopedic screws and evaluated their properties. The study's findings reveal that chemical oxidation of SiC activated its surface, enabling 3D printing of orthopedic screws in a binder jet printer. Post-processing impregnation with NaOH and/or NH4OH strengthened the scaffold by promoting silica crystallization or partial conversion of silicon oxide into silicon nitride. The silica surface of the SiC 3D printed orthopedic screws facilitated osteoblast and neuron adhesion and extensive axon synthesis. The silicate ions released from the 3D printed SiC screws favorably modulated macrophage immune responses toward an M1 phenotype as indicated by the inhibition of TNFα secretions and of reactive oxygen species (ROS) expression along with the promotion of IL6R shedding. In contrast, under the same experimental conditions, Ti ions released from Ti6Al4V discs promoted macrophage TNFα secretion and ROS expression. In vivo tests demonstrated direct bone deposition on the SiC scaffold and a strong interfacial bond between the implanted SiC and bone. Immunostaining showed innervation, mineralization, and vascularization of the newly formed bone at the interface with SiC. Taken altogether, the 3D printed SiC orthopedic screws foster a favorable environment for wound healing and bone regeneration. The novel 3D printing method, based on ceramic surface activation represents a significant advancement in ceramic additive manufacturing and is applicable to a wide variety of materials.

Extrusion 3D-printed tricalcium phosphate-polycaprolactone biocomposites for quercetin-KCl delivery in bone tissue engineering.

Critical-sized bone defects pose a significant challenge in advanced healthcare due to limited bone tissue regenerative capacity. The complex interplay of numerous overlapping variables hinders the development of multifunctional biocomposites. Phytochemicals show promise in promoting bone growth, but their dose-dependent nature and physicochemical properties halt clinical use. To develop a comprehensive solution, a 3D-printed (3DP) extrusion-based tricalcium phosphate-polycaprolactone (TCP-PCL) scaffold is augmented with quercetin and potassium chloride (KCl). This composite material demonstrates a compressive strength of 30 MPa showing promising stability for low load-bearing applications. Quercetin release from the scaffold follows a biphasic pattern that persists for up to 28 days, driven via diffusion-mediated kinetics. The incorporation of KCl allows for tunable degradation rates of scaffolds and prevents the initial rapid release. Functionalization of scaffolds facilitates the attachment and proliferation of human fetal osteoblasts (hfOB), resulting in a 2.1-fold increase in cell viability. Treated scaffolds exhibit a 3-fold reduction in osteosarcoma (MG-63) cell viability as compared to untreated substrates. Ruptured cell morphology and decreased mitochondrial membrane potential indicate the antitumorigenic potential. Scaffolds loaded with quercetin and quercetin-KCl (Q-KCl) demonstrate 76% and 89% reduction in bacterial colonies of Staphylococcus aureus, respectively. This study provides valuable insights as a promising strategy for bone tissue engineering (BTE) in orthopedic repair.

Advanced 3D printed bone scaffolds with sodium alginate/Tri-calcium phosphate/probiotic bacterial hydroxyapatite: Enhanced mechanical and biocompatible properties for bone tissue engineering

IntroductionThe increasing prevalence of severe bone diseases, such as osteoporosis and critical bone defects, necessitates the development of more effective bone substitutes. This study addresses this need by investigating 3D-printed bone scaffolds composed of sodium alginate and tricalcium phosphate, enhanced with three distinct types of hydroxyapatite (HA): bovine-derived HA, commercially available HA, and HA enriched with probiotic bacteria. We aim to evaluate the performance of these scaffolds in terms of mechanical strength, biocompatibility, and their ability to support bone regeneration. MethodsThe scaffolds were analyzed through various tests, including X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) to characterization. Scanning Electron Microscopy (SEM) was used to examine pore structure, while swelling and degradation tests evaluated the scaffold's stability. Compression testing determined mechanical strength, and in vitro cell culture assays assessed cell proliferation, osteogenic differentiation, and biomineralization. ResultsSEM results indicated that 3D scaffolds with probiotic bacterial HA had the desired 472 μm pore size. These scaffolds demonstrated a strain of 29.26 % and a compressive strength of 10 MPa, meeting the mechanical standards of human trabecular bone. Cell culture studies revealed enhanced cell proliferation by 50 %, osteogenic differentiation with 15.3 U/mg ALP activity, and 1.22-fold biomineralization, suggesting they are highly biocompatible and promote bone growth. ConclusionProbiotic bacterial HA scaffolds exhibit ideal properties and biocompatibility, enhancing bone regeneration and serving as an ideal alternative to chemical types.

Mitigating aging and doxorubicin induced bone loss in mature mice via mechanobiology based treatments

Aging leads to a reduced anabolic response to mechanical stimuli and a loss of bone mass and structural integrity. Chemotherapy agents such as doxorubicin exacerbate the degeneration of aging skeleton and further subject older cancer patients to a higher fracture risk. To alleviate this clinical problem, we proposed and tested a novel mechanobiology-based therapy. Building upon prior findings that i) Yoda1, the Piezo1 agonist, promoted bone growth in young adult mice and suppressed bone resorption markers in aged mice, and ii) moderate tibial loading protected bone from breast cancer-induced osteolysis, we hypothesized that combined Yoda1 and moderate loading would improve the structural integrity of adult and aged skeletons in vivo and protect bones from deterioration after chemotherapy. We first examined the effects of 4-week Yoda1 (dose 5 mg/kg, 5 times/week) and moderate tibial loading (4.5 N peak load, 4 Hz, 300 cycles for 5 days/week), individually and combined, on mature mice (∼50 weeks of age). Combined Yoda1 and loading was found to mitigate age-associated cortical and trabecular bone loss better than individual interventions. As expected, the non-treated controls experienced an average drop of cortical polar moment of inertia (Ct.pMOI) by −4.3 % over four weeks and the bone deterioration occurred in the majority (64 %) of the samples. Relative to no treatment, loading alone, Yoda1 alone, and combined Yoda1 and loading increased Ct.pMOI by +7.3 %, +9.5 %, +12.0 % and increased the % of samples with positive Ct.pMOI changes by +32 %, +26 %, and +43 %, respectively, suggesting an additive protection of aging-related bone loss for the combined therapy. We further tested if the treatment efficacy was preserved in mature mice following two weeks (six injections) of doxorubicin at the dose of 2.5 or 5 mg/kg. As expected, doxorubicin increased osteocyte apoptosis, altered bone remodeling, and impaired bone structure. However, the effects induced by DOX were too severe to be rescued by Yoda1 and loading, alone or combined, although loading and Yoda1 individually, or combined, increased the number of mice showing positive responsiveness by 0 %, +15 %, and +29 % relative to no intervention after doxorubicin exposure. Overall, this study supported the potentials and challenges of the Yoda1-based strategy in mitigating the detrimental skeletal effects caused by aging and doxorubicin.

Cellular transitions during cranial suture establishment in zebrafish

Cranial sutures separate neighboring skull bones and are sites of bone growth. A key question is how osteogenic activity is controlled to promote bone growth while preventing aberrant bone fusions during skull expansion. Using single-cell transcriptomics, lineage tracing, and mutant analysis in zebrafish, we uncover key developmental transitions regulating bone formation at sutures during skull expansion. In particular, we identify a subpopulation of mesenchyme cells in the mid-suture region that upregulate a suite of genes including BMP antagonists (e.g. grem1a) and pro-angiogenic factors. Lineage tracing with grem1a:nlsEOS reveals that this mid-suture subpopulation is largely non-osteogenic. Moreover, combinatorial mutation of BMP antagonists enriched in this mid-suture subpopulation results in increased BMP signaling in the suture, misregulated bone formation, and abnormal suture morphology. These data reveal establishment of a non-osteogenic mesenchyme population in the mid-suture region that restricts bone formation through local BMP antagonism, thus ensuring proper suture morphology.

Complex ontogeny of sexual size dimorphism in a female-larger gecko: Implications of determinate growth for lizard body size and life-history evolution.

Ectothermic vertebrates such as reptiles were assumed to be indeterminate growers, which means that there is no terminal point in time or size for growth in their lifetime. In recent years, evidence for the determinate nature of growth in lizards has accumulated, necessitating a re-examination of models of their ontogeny and evolution of sexual size dimorphism (SSD). In the female-larger gecko Paroedura vazimba, we monitored post-embryonic growth over a period of 15 months. After hatching, females grew faster than males but also reached their final body size, that is, closed growth of their vertebrae, earlier than males. The closure of bone growth in females correlates with the onset of reproductive maturation. We compared this pattern with the previously minutely studied, male-larger species Paroedura picta, where we documented determinate growth as well. We propose a model to explain the evolutionary switches in the direction of SSD in lizards based on bipotential effects of ovarian hormones on growth. In this model, male growth is assumed to require no male-specific growth modifier, such as sex-limited hormonal regulators, while growth is feminized by ovarian hormones in females. Low levels of ovarian hormones can promote bone growth, but high levels associated with maturation of the reproductive organs promote senescence of bone growth plates and thus cessation of bone growth. We suggest that models on growth, life-history and evolution of body size in many lizards should acknowledge their determinate nature of growth.

Optimization of the formulation of Tubiechong gel plaster and its effect on fracture healing by promoting angiogenesis in a rat model

Background and aimTransdermal drug delivery has been used in traditional Chinese medicine for thousands of years and is worth further developing. The purpose of this study was to investigate the preparation method of Tubiechong gel plaster (TGP) and evaluate its activity to promote fracture healing. Experimental procedureUsing rat skin as a barrier, and the human umbilical vein endothelial cells (HUVECs) proliferation promotion rate of the receiving solution as the evaluation index, the in vitro permeability of the plaster was studied by Franz diffusion cell method. A modified Einhorn method was used to model rat tibia fractures. The bone healing process was monitored by radiography. Bone development and angiogenesis were assessed by Safranin O Fast Green staining and CD31 immunohistochemistry, respectively. Serum bone metabolites and VEGF levels were determined by ELISA method. Results and conclusionThe optimal dose of azone for TGP is 2 %. The transdermal penetration equation for this plaster is consistent with the Ritger-Peppas equation. The prepared plaster was stable for at least 3 months. X-ray images showed that the fracture healing was promoted by TGP in a dose-related form at all periods. Serum BALP, OC, CTX-I, and VEGF levels also indicated better fracture healing after treatment. TGP significantly stimulated angiogenesis and bone growth at the fracture site on days 7,14 and 21, and the effect of promoting bone growth was shown on the third day. These data prove that the prepared Tubiechong gel plasters can promote fracture healing by promoting angiogenesis.

Advancements in Custom 3D-Printed Titanium Interbody Spinal Fusion Cages and Their Relevance in Personalized Spine Care.

3D-printing technology has revolutionized spinal implant manufacturing, particularly in developing personalized and custom-fit titanium interbody fusion cages. These cages are pivotal in supporting inter-vertebral stability, promoting bone growth, and restoring spinal alignment. This article reviews the latest advancements in 3D-printed titanium interbody fusion cages, emphasizing their relevance in modern personalized surgical spine care protocols applied to common clinical scenarios. Furthermore, the authors review the various printing and post-printing processing technologies and discuss how engineering and design are deployed to tailor each type of implant to its patient-specific clinical application, highlighting how anatomical and biomechanical considerations impact their development and manufacturing processes to achieve optimum osteoinductive and osteoconductive properties. The article further examines the benefits of 3D printing, such as customizable geometry and porosity, that enhance osteointegration and mechanical compatibility, offering a leap forward in patient-specific solutions. The comparative analysis provided by the authors underscores the unique challenges and solutions in designing cervical, and lumbar spine implants, including load-bearing requirements and bioactivity with surrounding bony tissue to promote cell attachment. Additionally, the authors discuss the clinical outcomes associated with these implants, including the implications of improvements in surgical precision on patient outcomes. Lastly, they address strategies to overcome implementation challenges in healthcare facilities, which often resist new technology acquisitions due to perceived cost overruns and preconceived notions that hinder potential savings by providing customized surgical implants with the potential for lower complication and revision rates. This comprehensive review aims to provide insights into how modern 3D-printed titanium interbody fusion cages are made, explain quality standards, and how they may impact personalized surgical spine care.

LL-37 and bisphosphonate co-delivery 3D-scaffold with antimicrobial and antiresorptive activities for bone regeneration

This study introduces a novel 3D scaffold for bone regeneration, composed of silk fibroin, chitosan, nano-hydroxyapatite, LL-37 antimicrobial peptide, and pamidronate. The scaffold addresses a critical need in bone tissue engineering by simultaneously combating bone infections and promoting bone growth. LL-37 was incorporated for its broad-spectrum antimicrobial properties, while pamidronate was included to inhibit bone resorption. The scaffold's porous structure, essential for cell infiltration and nutrient diffusion, was achieved through a freeze-drying process. In vitro assessments using SEM and FTIR confirmed the scaffold's morphology and chemical integrity. Antimicrobial efficacy was tested against pathogens of Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa). In vivo studies in a murine model of infectious bone defect revealed the scaffold's effectiveness in reducing inflammation and bacterial load, and promoting bone regeneration. RNA sequencing of treated specimens provided insights into the molecular mechanisms underlying these observations, revealing significant gene expression changes related to bone healing and immune response modulation. The results indicate that the scaffold effectively inhibits bacterial growth and supports bone cell functions, making it a promising candidate for treating infectious bone defects. Future studies should focus on optimizing the release of therapeutic agents and evaluating the scaffold's clinical potential.

Micro-Computed Tomography Analysis and Histological Observation of the Screw-Bone Interface of Novel Porous Scaffold Core Pedicle Screws and Hollow Lateral Hole Pedicle Screws: A Comparative Study in Bama Pigs

Screw loosening is a common complication of pedicle screw internal fixation surgery. This study aimed to investigate whether the application of a porous scaffold structure can increase the contact area between screws and bone tissue by comparing the bone ingrowth and screw-bone interface of porous scaffold core pedicle screws (PSCPSs) and hollow lateral hole pedicle screws (HLHPSs) in the lumbar spine of Bama pigs. Sixteen pedicle screws of both types were implanted into the bilateral pedicles of the L1-4 vertebrae of 2 Bama pigs. All Bama pigs were sacrificed and the lumbar spine was freed into individual vertebrae at 16weeks postoperatively. After the vertebrae were made into screw-centered specimens, micro-computed tomography analysis and histological observation were performed to assess the screw-bone interface and bone growth around and within the screws. We found that the bone condition around PSCPSs and HLHPSs did not show significant differences on micro-computed tomography three-dimensional reconstruction images. CT transverse views showed different bone growth inside the 2 screws. In PSCPSs, bone tissue was seen to fill the internal pores and was evenly distributed around each strut. Inside HLHPSs, bone growth was confined to 1 side of the screw and did not fill the entire cavity. Osteometric analysis showed that bone volume fraction and trabecular number, the parameters representing bone mass, were higher in PSCPSs than in HLHPSs. These differences were not statistically significant (P > 0.05). Histological observations visualized that the osseointegration within PSCPSs was superior to that of HLHPSs, and the tight integration of bone tissue with the porous scaffold resulted in a larger screw-bone integration area in PSCPSs than in HLHPSs. Compared with HLHPSs, PSCPSs possessing a porous scaffold core could promote bone ingrowth and osseointegration, resulting in an effective enhancement of the combined area of the screw-bone interface.

Hydrolyzed egg yolk powder promotes bone growth and development in rats: A multidimensional mechanistic study

Given the growing worldwide focus on bone health, exploring safe and effective interventions to maintain skeletal integrity is imperative. This study involved intragastrically administering hydrolyzed egg yolk powder (HEYP) to 3-week-old Sprague‒Dawley (SD) rats over a period of six weeks. The effects of HEYP on bone growth and the underlying mechanisms were comprehensively investigated by evaluating known bone growth parameters, bone microstructural features, serum biochemical parameters, the metabolome, and the gut microbiome. HEYP administration significantly increased longitudinal bone growth while concurrently increasing the serum levels of osteogenic growth factors. Subsequent metabolomic analyses revealed significant alterations in the serum levels of metabolites associated with bone metabolism, highlighting the profound impact of HEYP on amino acid metabolism. Additionally, gut microbiome analyses revealed HEYP-induced changes in the gut microbiota (GM), identifying key bacterial genera, including Blautia, Parasutterella, Marvinbryantia and Prevotella, that were potentially beneficial for bone formation and linked to bone growth. Correlation analyses further highlighted associations between significantly altered serum metabolites, distinct bacterial genera, and bone growth-related parameters. These findings emphasized that HEYP might promote bone growth through various pathways, offering insights into the potential development and application of functional foods that promote bone health and potentially aid in osteoporosis prevention.

3D-printed Mg-incorporated PCL-based scaffolds improves rotator cuff tendon-bone healing through regulating macrophage polarization.

Introduction: Rotator cuff tear (RCT) is a common shoulder injury impacting mobility and quality of life, while traditional surgeries often result in poor healing. Tissue engineering offers a promising solution, with poly (ε-caprolactone) (PCL) being favored due to its slow degradation, biocompatibility, and non-toxicity. However, PCL lacks sufficient compression resistance. Incorporating Mg, which promotes bone growth and has antibacterial effects, could enhance RCT repair. Methods: The Mg-incorporated PCL-based scaffolds were fabricated using a 3D printing technique. The scaffolds were incorporated with different percentages of Mg (0%, 5%, 10%, 15%, and 20%). The osteogenic activities and anti-inflammatory properties of the scaffolds were evaluated in vitro using human osteoblasts and macrophages. The tissue ingrowth and biocompatibility of the scaffolds were assessed in vivo using a rat model of RCT repair. The ability of the scaffolds to enhance macrophage polarization towards the M2 subtype and inhibit inflammation signaling activation was also investigated. Results: It was found that when incorporated with 10% Mg, PCL-based scaffolds exhibited the optimal bone repairing ability in vitro and in vivo. The in vitro experiments indicated that the successfully constructed 10Mg/PCL scaffolds enhance osteogenic activities and anti-inflammatory properties. Besides, the in vivo studies demonstrated that 10Mg/PCL scaffolds promoted tissue ingrowth and enhanced biocompatibility compared to the control PCL scaffolds. Furthermore, the 10Mg/PCL scaffolds enhanced the macrophages' ability to polarize towards the M2 subtype and inhibited inflammation signaling activation. Discussion: These findings suggest that 3D-printed Mg-incorporated PCL scaffolds have the potential to improve RCT by enhancing osteogenesis, reducing inflammation, and promoting macrophage polarization. The incorporation of 10% Mg into PCL-based scaffolds provided the optimal combination of properties for RCT repair augmentation. This study highlights the potential of tissue engineering approaches in improving the outcomes of RCT repair and provides a foundation for future clinical applications.

A Gelatin-Based Biomimetic Scaffold Promoting Osteogenic Differentiation of Adipose-Derived Mesenchymal Stem Cells.

In bone tissue engineering segment, numerous approaches have been investigated to address critically sized bone defects via 3D scaffolds, as the amount of autologous bone grafts are limited, accompanied with complications on harvesting. Moreover, the use of bone-marrow-derived stem cells is also a limiting factor owing to the invasive procedures involved and the low yield of stem cells. Hence, research is ongoing on the search for an ideal bone graft system promoting bone growth and regeneration. This study aims to develop a unique platform for tissue development via stem cell differentiation towards an osteogenic phenotype providing optimum biological cues for cell adhesion, differentiation and proliferation using biomimetic gelatin-based scaffolds. The use of adipose-derived mesenchymal stem cells in this study also offers an ideal approach for the development of an autologous bone graft. A gelatin-vinyl acetate-based 3D scaffold system incorporating Bioglass was developed and the osteogenic differentiation of adipose-derived mesenchymal stem cells (ADMSCs) on the highly porous freeze-dried gelatin-vinyl acetate/ Bioglass scaffold (GB) systemwas analyzed. The physicochemical properties, cell proliferation and viability were investigated by seeding rat adipose tissue-derived mesenchymal stem cells (ADSCs) onto the scaffolds. The osteogenic differentiation potential of the ADMSC seeded GeVAc/bioglass system was assessed using calcium deposition assay and bone-related protein and genes and comparing with the 3D Gelatin vinyl acetate coppolymer (GeVAc) constructs. According to the findings, the 3D porous GeVAc/bioglass scaffold can be considered as a promising matrix for bone tissue regeneration and the 3D architecture supports the differentiation of the ADMSCs into osteoblast cells and enhances the production of mineralized bone matrix.

Mechanistic study on the role of 3D-Printed biomimetic coral bone scaffolds in bone defect repair

With the continuous innovation and development of 3D printing technology, 3D-printed biomimetic coral bone scaffolds have demonstrated significant potential in the field of bone defect repair. This paper aims to explore in-depth the mechanistic study of 3D-printed biomimetic coral bone scaffolds in bone defect repair, by systematically reviewing relevant literature and analyzing their potential mechanisms in promoting bone growth and improving the success rate of bone defect repair. Firstly, this paper introduces the fabrication process and material characteristics of 3D-printed biomimetic coral bone scaffolds. Secondly, the paper discusses the mechanisms of 3D-printed biomimetic coral bone scaffolds in terms of biocompatibility, biomechanical performance, as well as their roles in vascularization and bone formation. Finally, the paper outlines future research directions for 3D-printed biomimetic coral bone scaffolds, including further optimization of material properties, improvement of printing precision, and expansion of clinical applications.

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.

Use of allograft bone matrix in clinical orthopedics.

Clinical orthopedics continuously aims to improve methods for bone formation. Clinical applications where bone formation is necessary include critical long bone defects in orthopedic trauma or tumor patients. Though some biomaterials combined with autologous stem cells significantly improve bone repair, critical-size damages are still challenged with the suitable implantation of biomaterials and donor cell survival. Extracellular matrix (ECM) is the fundamental structure in tissues that can nest and nourish resident cells as well as support specific functions of the tissue type. ECM also plays a role in cell signaling to promote bone growth, healing and turnover. In the last decade, the use of bone-derived ECMs or ECM-similar biomaterials have been widely investigated, including decellularized and demineralized bone ECM. In this article, we reviewed the current productions and applications of decellularized and demineralized bone matrices. We also introduce the current study of whole limb decellularization and recellularization.

Investigating Novel Therapeutic Approaches for Idiopathic Short Stature: Targeting siRNA and Growth Hormone Delivery to the Growth Plate Using Exosome Nanoparticles.

Idiopathic short stature (ISS) is a common childhood condition with largely unknown underlying causes. Recent research highlights the role of circulating exosomes in the pathogenesis of various disorders, but their connection to ISS remains unexplored. In the experiments, human chondrocytes are cocultured with plasma exosomes from ISS patients, leading to impaired chondrocyte growth and bone formation. Elevated levels of a specific long non-coding RNA (lncRNA), ISSRL, are identified as a distinguishing factor in ISS, boasting high specificity and sensitivity. Silencing ISSRL in ISS plasma exosomes reverses the inhibition of chondrocyte proliferation and bone formation. Conversely, overexpression of ISSRL in chondrocytes impedes their growth and bone formation, revealing its mechanism of action through the miR-877-3p/GZMB axis. Subsequently, exosomes (CT-Exo-siISSRL-oeGH) with precise cartilage-targeting abilities are engineered, loaded with customized siRNA for ISSRL and growth hormone. This innovative approach offers a therapeutic strategy to address ISS by rectifying abnormal non-coding RNA expression in growth plate cartilage and delivering growth hormone with precision to promote bone growth. This research provides valuable insights into ISS diagnosis and treatment, highlighting the potential of engineered exosomes.