Treatment Of Bone Defects Research Articles

Treatment of Bone Defects and Nonunion via Novel Delivery Mechanisms, Growth Factors, and Stem Cells: A Review.

Bone nonunion following a fracture represents a significant global healthcare challenge, with an overall incidence ranging between 2 and 10% of all fractures. The management of nonunion is not only financially prohibitive but often necessitates invasive surgical interventions. This comprehensive manuscript aims to provide an extensive review of the published literature involving growth factors, stem cells, and novel delivery mechanisms for the treatment of fracture nonunion. Key growth factors involved in bone healing have been extensively studied, including bone morphogenic protein (BMP), vascular endothelial growth factor (VEGF), and platelet-derived growth factor. This review includes both preclinical and clinical studies that evaluated the role of growth factors in acute and chronic nonunion. Overall, these studies revealed promising bridging and fracture union rates but also elucidated complications such as heterotopic ossification and inferior mechanical properties associated with chronic nonunion. Stem cells, particularly mesenchymal stem cells (MSCs), are an extensively studied topic in the treatment of nonunion. A literature search identified articles that demonstrated improved healing responses, osteogenic capacity, and vascularization of fractures due to the presence of MSCs. Furthermore, this review addresses novel mechanisms and materials being researched to deliver these growth factors and stem cells to nonunion sites, including natural/synthetic polymers and bioceramics. The specific mechanisms explored in this review include BMP-induced osteoblast differentiation, VEGF-mediated angiogenesis, and the role of MSCs in multilineage differentiation and paracrine signaling. While these therapeutic modalities exhibit substantial preclinical promise in treating fracture nonunion, there remains a need for further research, particularly in chronic nonunion and large animal models. This paper seeks to identify such translational hurdles which must be addressed in order to progress the aforementioned treatments from the lab to the clinical setting.

Effect of Structure on Osteogenesis of Bone Scaffold: Simulation Analysis Based on Mechanobiology and Animal Experiment Verification

Porous scaffolds, whose mechanical and biological properties are greatly affected by structure, are new treatments for bone defects. Since bone repair is related to biomechanics, analyzing the osteogenesis in scaffolds based on mechanical stimulation may become a more effective method than traditional biological experiments. A tissue regeneration algorithm based on mechanical regulation theory was implemented in this study to evaluate the osteogenesis of classical scaffolds (Gyroid, I-WP, and Diamond). In vivo experiments were used to verify and supplement the simulation results. Different approaches to describing osteogenesis were discussed. Bone formation was more obvious inside the Gyroid scaffold and outside the I-WP scaffold, while the new bone was more sufficient and evenly distributed in the Diamond scaffold. The osteogenesis pattern of the bone scaffold in the simulation analysis was consistent with the results of animal experiments, and the bone volume calculated by the tissue fraction threshold method and the elastic modulus threshold method was very similar to the in vivo experiment. The mechanical responses mediated by structure affect the osteogenesis of bone scaffolds. This study provided and confirmed a simulation analysis method based on mechanical regulation theory, which is more efficient and economical for analyzing tissue healing in bioengineering.

Lost in translation: the lack of agreement between surgeons and scientists regarding biomaterials research and innovation for treating bone defects

BackgroundWith over 2 million grafts performed annually, bone ranks second only to blood in the frequency of transplants. This high demand is primarily driven by the persistent challenges posed by bone defects, particularly following trauma or surgical interventions such as tumour excision. The demand for effective and efficient treatments has increased exponentially in the twenty-first century. Limitations associated with autologous bone grafts drive exploration into replacements, including allografts, synthetic substitutes, and 3D-printed scaffolds. This research aimed to unravel disparities in the knowledge and evaluation of current and future bone defect treatments between surgeons and biomaterial scientists.MethodsA prospective cross-sectional survey, pre-registered with the OSF (https://osf.io/y837m/?view_only=fab29e24df4f4adf897353ac70aa3361) and conducted online from October 2022 to March 2023, collected data on surgeons’ views (n = 337) and scientists (n = 99) on bone defect treatments.ResultsScientists were significantly more optimistic than surgeons regarding the future replacement of autologous bone grafts with synthetic or tissue-engineered substitutes (p < 0.001). Accordingly, scientists foresee a paradigm shift from autologous bone grafts to biomaterial and tissue-engineered solutions, reflecting their confidence in the ongoing advancements within this field.Furthermore, regulatory trepidations for 3D-printed bone scaffolds were acknowledged, with scientists emphasizing the need for a more significant focus on clinical relevance in preclinical studies and regulatory clarity. In a ranked categorical assessment, witnessing the technology in action was deemed most influential in adopting new bone regeneration methods by both scientists and surgeons.ConclusionsTo conclude, this study was conducted through a web-based survey, highlighting a substantial translational gap. It underscores the immediate need (“call to action”) for meaningful interdisciplinary collaboration between surgeons and scientists, often referred to as the need to “walk the talk”. The findings underscore the critical importance of aligning clinical needs, research outcomes, and regulatory frameworks to improve the development and implementation of biomaterial-based bone graft substitutes that demonstrate efficacy and efficiency in bone defect treatment.

Electron-donable heterojunctions with synergetic Ru-Cu pair sites for biocatalytic microenvironment modulations in inflammatory mandible defects

The clinical treatments of maxillofacial bone defects pose significant challenges due to complex microenvironments, including severe inflammation, high levels of reactive oxygen species (ROS), and potential bacterial infection. Herein, we propose the de novo design of an efficient, versatile, and precise electron-donable heterojunction with synergetic Ru-Cu pair sites (Ru-Cu/EDHJ) for superior biocatalytic regeneration of inflammatory mandible defects and pH-controlled antibacterial therapies. Our studies demonstrate that the unique structure of Ru-Cu/EDHJ enhances the electron density of Ru atoms and optimizes the binding strength of oxygen species, thus improving enzyme-like catalytic performance. Strikingly, this biocompatible Ru-Cu/EDHJ can efficiently switch between ROS scavenging in neutral media and ROS generation in acidic media, thus simultaneously exhibiting superior repair functions and bioadaptive antibacterial properties in treating mandible defects in male mice. We believe synthesizing such biocatalytic heterojunctions with exceptional enzyme-like capabilities will offer a promising pathway for engineering ROS biocatalytic materials to treat trauma, tumors, or infection-caused maxillofacial bone defects.

Biological evaluation of ZrO2 composites modified with different ceramics additives

In this work, zirconia (ZrO2) composites modified with bioactive hydroxyapatite (HAp), hexagonal boron nitride (hBN), bioglass (BG), and bioglass with copper (BGCu) via the hydrothermal method were synthesized. The aim was to obtain highly bioactive and cytocompatible materials that could combine beneficial properties of inert and bioactive ceramics. Such materials could be applied as fillers for tooth extraction cavities, guaranteeing osseintegration without the need to introduce additional bone cements or other adhesives. It was proven that while all materials were favourable towards cells adhesion and growth, the HAp and BG-doped ones facilitated early adhesion, especially when compared to unmodified ZrO2. Only the HAp-doped materials showed satisfactory bioactivity results, with a well-developed apatite layer forming on their surfaces. This study confirms that the Hap-doped ZrO2 is suitable for treating bone defects.

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.

Synergy of engineered gelatin methacrylate-based porous microspheres and multicellular assembly to promote osteogenesis and angiogenesis in bone tissue reconstruction

One of the key challenges in bone defects treatment is providing adequate and stable blood supply during new tissue regeneration. Mesenchymal stem cells (MSCs) and endothelial cells (ECs) have great potential to promote osteogenesis and angiogenesis during bone defect repair through paracrine effects, but their therapeutic efficacy depends on effective cellular assembly and delivery. In this work, we developed various microspheres with different pore sizes for multi-cellular delivery to enhance the angiogenic and osteogenic capability via combining microfluidic and gradient freeze-drying techniques. The particle and pore size of fabricated porous gelatin methacrylate (GelMA)-based hydrogel microspheres (PGMS) could be controllable through adjusting the freezing time of hydrogel microspheres, the range of particles and pores size are 150–250 μm and 10–100 μm with different freezing time from 0 min to 30 min. The optimized particle size (200.8 ± 14.2 μm) and pore size (11.2 ± 1.9 μm) were explored to promote cell assemble, adhesion, growth, and proliferation in the PGMS. Furthermore, the co-assembly and delivery of bone marrow mesenchymal stem cells (BMSCs) and human umbilical vein endothelial cells (HUVECs) on the PGMS was achieved and an optimal cellular ratio of BMSCs to HUVECs (20:2) was established for co-culturing of them to achieve optimal paracrine effects, further promoting osteogenic differentiation and angiogenesis. Finally, results from both in vitro and in vivo experiments showed that the developed PGMS with co-assembly of BMSCs to HUVECs contributed to accelerate bone regeneration and vascularization process daringly, exhibited great potential in vascularized bone tissue reconstruction.

Enhanced Mandibular Bone Repair Using Poly Lactic-co-glycolic Acid Combined with Nanohydroxyapatite Scaffold Loaded by Mesenchymal Stromal/Stem Cells and Curcumin in Male Rats.

This study aimed to investigate the healing effect of a polylactic-co-glycolic acid (PLGA) scaffold containing nanohydroxyapatite (NHA) along with curcumin (CCM), loaded with adipose-derived mesenchymal stem cells (AD-MSCs), on mandibular bone defects. The designed PLGA scaffolds containing NHA were evaluated for their mechanical and structural properties. Forty rats were divided into five groups (n = 8) based on the treatment: Sham, PLGA scaffolds containing NHA, PLGA scaffolds containing NHA + CCM, PLGA scaffolds containing NHA + AD-MSCs, and PLGA scaffolds containing NHA + CCM + AD-MSCs. After 8 weeks' follow-up, mandible bones were isolated for histomorphometry evaluation. Data were analyzed using SPSS version 21, with p-values <0.05 considered statistically significant. SEM evaluation showed that the designed nanocomposite scaffold had 80% porosity. Histomorphometry results indicated a significant difference in osteocyte, osteoblast, bone area, and vascular area parameters in the group treated with scaffolds loaded with AD-MSCs + CCM compared to the other groups (p < 0.05). The PLGA-containing NHA-CCM nanocomposite scaffold demonstrated good porosity and dispersion, suitable for treating bone defects. Rats treated with scaffolds containing AD-MSCs and CCM showed better therapeutic results than the other groups. Further research is needed to evaluate its anti-inflammatory, antioxidant properties, osteogenesis, and therapeutic effects in larger animal models.

Concrete-Inspired Bionic Bone Glue Repairs Osteoporotic Bone Defects by Gluing and Remodeling Aging Macrophages.

Osteoporotic fractures are characterized by abnormal inflammation, deterioration of the bone microenvironment, weakened mechanical properties, and difficulties in osteogenic differentiation. The chronic inflammatory state characterized by aging macrophages leads to delayed or non-healing of the fracture or even the formation of bone defects. The current bottleneck in clinical treatment is to achieve strong fixation of the comminuted bone fragments and effective regulation of the complex microenvironment of aging macrophages. Inspired by cement and gravel in concrete infrastructure, a biomimetic bone glue with poly(lactic-co-glycolic acid) microspheres is developed and levodopa/oxidized chitosan hydrogel stabilized on an organic-inorganic framework of nanohydroxyapatite, named DOPM. DOPM is characterized via morphological and mechanical characterization techniques, in vitro experiments with bone marrow mesenchymal stromal cells, and in vivo experiments with an aged SD rat model exhibiting osteoporotic bone defects. DOPM exhibited excellent adhesion properties, good biocompatibility, and significant osteogenic differentiation. Transcriptomic analysis revealed that DOPM improved the inflammatory microenvironment by inhibiting the NF-κB signaling pathway and promoting aging macrophage polarization toward M2 macrophages, thus significantly accelerating bone defect repair and regeneration. This biomimetic bone glue, which enhances osteointegration and reestablishes the homeostasis of aging macrophages, has potential applications in the treatment of osteoporotic bone 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.

Revolutionizing bone defect healing: the power of mesenchymal stem cells as seeds.

Bone defects can arise from trauma or pathological factors, resulting in compromised bone integrity and the loss or absence of bone tissue. As we are all aware, repairing bone defects is a core problem in bone tissue engineering. While minor bone defects can self-repair if the periosteum remains intact and normal osteogenesis occurs, significant defects or conditions such as congenital osteogenesis imperfecta present substantial challenges to self-healing. As research on mesenchymal stem cell (MSC) advances, new fields of application have emerged; however, their application in orthopedics remains one of the most established and clinically valuable directions. This review aims to provide a comprehensive overview of the research progress regarding MSCs in the treatment of diverse bone defects. MSCs, as multipotent stem cells, offer significant advantages due to their immunomodulatory properties and ability to undergo osteogenic differentiation. The review will encompass the characteristics of MSCs within the osteogenic microenvironment and summarize the research progress of MSCs in different types of bone defects, ranging from their fundamental characteristics and animal studies to clinical applications.

Characterization of marine hydroxyapatite and its interest in bone filling in rabbits femoral defect model: In vivo, in vitro, and in silico study

PurposeHydroxyapatite (HA) is a promising scaffold material for bone defect treatment. This study aimed to evaluate the physicochemical and biological properties of a novel marine-derived HA extracted from blue fish scales and assess its potential as a bone substitute for clinical use. Methods80 female New Zealand white rabbits were assigned to 4 groups (n = 20): HA powder (EC group), 3D-printed HA cylinder (I3DFFF group), negative control group (NC group; bone defect without biomaterial), and positive control group (PC group; bone defect treated with commercially synthesized HA). The biomaterials were characterized in vitro using X-ray diffraction, nitrogen adsorption, scanning electron microscopy, emission spectrophotometry, and MTT assays. In vivo evaluation involved the same techniques, supplemented with histological and radiological analyses at 1, 3, 6, and 9 months post-implantation. Molecular docking studies were also performed to investigate HA's effect on RANKL-induced osteoclastogenesis and the NF-κB signaling pathway. ResultsIn vitro characterization showed that marine-derived HA is a mesoporous material with a crystalline structure similar to natural bone. In vivo, the material demonstrated biocompatibility, osteoinductivity, and osteoconductivity, providing a supportive environment for bone regeneration. Molecular docking indicated that HA could inhibit osteoclastogenesis by suppressing the NF-κB signaling pathway. ConclusionOur findings suggest that the two co-products, EC-17 and I3DFFF, possess the necessary physicochemical and biological characteristics to be developed as effective bone substitutes.

Serum biochemical evaluation of healing of critical-sized long bone defects in rats treated with biphasic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) bioceramic scaffolds

Critical-sized long bone defects are those that would not heal spontaneously despite surgical stabilisation. The use of bioceramic scaffold has shown promising results in the repair of bone defects. The present study was undertaken to evaluate the serum biochemical parameters of Wistar rats treated for critical-sized segmental bone loss using biphasic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) bioceramic scaffolds. The study was conducted in eighty male Wistar rats aged between 8-12 weeks, weighing 200-250 g body weight with critical-sized segmental defects in the femur. A 6 mm segmental mid-diaphyseal femoral defect was created under general anaesthesia. The bone defect was bridged with bioceramic scaffolds and retained in position with microplate and screws. Serum biochemical parameters serum calcium, phosphorous, acid phosphatase and alkaline phosphatase were evaluated four weeks before surgery, immediately after surgery and 4th, 8th, 12th, and 16th week after surgery. The evaluation of both serum calcium and phosphorous were found to be reliable indicators of new bone formation and mineralisation, whereas the evaluation of both serum acid phosphatase and alkaline phosphatase were found to be reliable indicators of bone healing during the treatment of critical-sized long bone defects in rats using biphasic hydroxyapatite and β-tricalcium phosphate bioceramic scaffolds Keywords: Beta-tricalcium phosphate, bioceramic scaffold, hydroxyapatite, serum acid phosphatase, serum alkaline phosphatase, serum calcium, serum phosphorous

Biomechanical evaluation of healing of critical-sized long bone defects in rats treated with biphasic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) bioceramic scaffolds

Critical-sized bone defects are those that would not heal spontaneously despite surgical stabilisation. These defects are treated using autografts, allografts, xenografts and synthetic bone grafts. The present study was undertaken to evaluate the efficacy of biphasic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) bioceramic scaffolds in treating critical-sized segmental bone loss in rats. The study was conducted in sixty male Wistar rats aged between 8-12 weeks, weighing 200-250 g body weight with critical-sized defects in the right femur. A six-mm segmental mid-diaphyseal femoral defect was created under general anaesthesia. The bone defect was bridged with biphasic hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) bioceramic scaffolds and retained in position with microplate and screws. Fifteen rats were sacrificed as per the guidelines of CCSEA during the 4th, 8th, 12th and 16th week post-surgery. The treated bone and contralateral femur were harvested and subjected to a three-point bending test, torsion test and compression test to compare the regained strength of the repaired right femur with that of the intact contralateral left femur. From the present study, it was observed that the use of biphasic hydroxyapatite and β-tricalcium phosphate bioceramic scaffolds in the treatment of critical-sized long bone defects in rats resulted in biomechanical properties of the healed right femur greatly superior to the femur with untreated critical-sized diaphyseal defect by sixteenth week post-surgery and was only slightly inferior to the normal intact left femur. The results were suggestive of using biphasic hydroxyapatite and β-tricalcium phosphate bioceramics scaffolds as a safe and promising alternative for the treatment of critical-sized bone defects Keywords: Beta-tricalcium phosphate, bioceramic scaffold, compression test, hydroxyapatite, three-point bending test and torsion test

Distraction osteogenesis application in bone defect caused by osteomyelitis following mandibular fracture surgery: a case report and literature review

BackgroundOsteomyelitis secondary to mandibular fracture surgery is rare and complete surgical debridement of necrotic infected tissues is an optimal treatment for it. Subsequent reconstruction is required for bone defect caused by operation. Autogenous, allograft and synthetic bone graft substitutes have become widespread in bone defect treatment. Distraction osteogenesis (DO) was also applied in bone defect reconstruction, even it wasn’t conventional therapy in jaw.Case presentationHere we report a case of a 40-year-old aged man who presented with chronic swelling and pain on the right mandibular masseteric region after mandibular angle and Le Fort II fracture surgery. In six weeks after surgery, CBCT images showed that the fracture ends hadn’t heal and the fracture gap had widened significantly. The clinical diagnosis of the patient was right mandibular angle osteomyelitis. After controlling the symptoms of pain and infection with local rinses and systemic antibiotic therapy, the patient underwent segmental resection of the infected bone and DO reconstruction for bone defect simultaneously. Encouragingly, well bone healing and normal occlusion restoration was observed finally.ConclusionsDO could be a valuable alternative therapy to bone grafts for bone defect, even in the case of infection.

Response of a Blood Clot Adherent to Bone, Oral Mucosa and Hard Dental Tissues to a Uniaxial Tensile Test: An In Vitro Study.

Background and Objectives: Periodontal therapy aims to arrest the progression of periodontal diseases and possibly to regenerate the periodontal apparatus. To shift healing from repair to regeneration, the blood clot that fills the periodontal defect and remains in contact with structures such as tooth root, mucosa and bone needs to be stable, which is a reason why the treatment of non-containing periodontal bone defects, in which the clot may undergo displacement, is challenging. The gingival soft tissue, properly sutured, may act as a wall for blood clot stabilization. Knowledge on the response of the blood clot to stress and how it might vary according to the characteristics of the tissues it gets in contact with might be deepened. The aim of this study was to investigate in vitro, by means of a micro-loading device, the response of the complex formed by a blood clot and diverse tissues, simulating those involved in periodontal regeneration, to a displacing tensile test. Materials and Methods: Experimental samples made of two layers of either hard dental tissues, cancellous bone or oral mucosa, between which fresh blood was interposed, underwent a debonding experiment by means of a micro-loading device that measured their response to uniaxial tensile stress. Results: The peak of tensile stress and the overall work needed for the complete rupture of the clot's fibrin filaments were significantly higher for hard dental tissues than for other tissues. However, mucosa sustained the highest maximal strain in terms of relative displacement between the plates of the micro-loading device to accomplish the complete rupture of the fibrin filaments compared to the other tissues, suggesting that the mucosa might act as a stable interface with the clot and be able to sustain tensile stresses. Conclusions: This in vitro study seems to support the use of mucosa to act as a wall for regenerative procedures of suprabony periodontal defects given its capability to form a stable interface with the clot.

Biomimetic Scaffolds Regulating the Iron Homeostasis for Remolding Infected Osteogenic Microenvironment.

The treatment of infected bone defects (IBDs) needs simultaneous elimination of infection and acceleration of bone regeneration. One mechanism that hinders the regeneration of IBDs is the iron competition between pathogens and host cells, leading to an iron deficient microenvironment that impairs the innate immune responses. In this work, an in situ modification strategy is proposed for printing iron-active multifunctional scaffolds with iron homeostasis regulation ability for treating IBDs. As a proof-of-concept, ultralong hydroxyapatite (HA) nanowires are modified through in situ growth of a layer of iron gallate (FeGA) followed by incorporation in the poly(lactic-co-glycolic acid) (PLGA) matrix to print biomimetic PLGA based composite scaffolds containing FeGA modified HA nanowires (FeGA-HA@PLGA). The photothermal effect of FeGA endows the scaffolds with excellent antibacterial activity. The released iron ions from the FeGA-HA@PLGA help restore the iron homeostasis microenvironment, thereby promoting anti-inflammatory, angiogenesis and osteogenic differentiation. The transcriptomic analysis shows that FeGA-HA@PLGA scaffolds exert anti-inflammatory and pro-osteogenic differentiation by activating NF-κB, MAPK and PI3K-AKT signaling pathways. Animal experiments confirm the excellent bone repair performance of FeGA-HA@PLGA scaffolds for IBDs, suggesting the promising prospect of iron homeostasis regulation therapy in future clinical applications.

Shape Memory Polymer Bioglass Composite Scaffolds Designed to Heal Complex Bone Defects.

An off-the-shelf scaffold with requisite properties could enable the viable treatment of irregular craniomaxillofacial bone defects. Notably, the scaffold should be conformally fitting, innately bioactive, and bioresorbable. In prior work, we developed a series of shape memory polymer (SMP) scaffolds based on cross-linked poly(ε-caprolactone) (PCL). These were capable of "self-fitting" into complex bone defects when exposed to temperatures above the melt transition of the constituent PCL, either linear-PCL-diacrylate (linear-PCL-DA, Tm ∼55 °C) or star-PCL-tetraacrylate (star-PCL-TA, Tm ∼45 °C) for the potential to improve tissue safety. To achieve favorably increased degradation rates versus PCL-only scaffolds, semi-interpenetrating networks (semi-IPNs) were formed by including linear- or star-poly(l-lactic acid) (PLLA). A potential limitation of these self-fitting scaffolds is the lack of bioactivity, which is essential to osteoinductivity and osseointegration. Herein, analogous composite scaffolds were formed with 45S5 bioglass (BG) to impart bioactivity. The solvent-cast particulate leaching fabrication method was adapted to introduce BG to the fused salt template, resulting in composites with BG concentrated on the pore wall surfaces rather than within pore struts. Composite scaffolds with good pore wall integrity were produced with 2.5, 5, and 10 wt % BG. All composite scaffolds exhibited non-brittle behavior and did not fracture with 85% strain. For semi-IPN composite scaffolds, PLLA crystallinity was lost, and mechanical properties were not appreciably altered versus the non-BG controls. Sufficient retention of PCL crystallinity led to excellent shape memory behavior. The inclusion of 5 and 10 wt % BG led to hydroxyapatite mineralization after 1 day of exposure to simulated body fluid, as well as increased rates of in vitro degradation.

Europium-Doped 3D Dimensional Porous Calcium Phosphate Scaffolds as a Strategy for Facilitating the Comprehensive Regeneration of Bone Tissue: In Vitro and In Vivo.

In response to the challenges faced by clinicians treating bone defects caused by various factors, various bone repair materials have been investigated, but the efficiency of bone healing still needs to be improved due to the acting of scaffolds only in a single stage of bone tissue regeneration. We investigated the potential of a novel 3D scaffold to support different stages of bone tissue regeneration, including initial inflammation, proliferation, and remodeling. Eu (0, 0.5, 2, 3.5, 5, and 6.5%) was added to calcium polyphosphate to obtain 3D porous network-doped Eu calcium polyphosphate (EuCPP) scaffolds with ideal mechanical strength and pore size. Both in vitro and in vivo experiments proved that Eu3+ released from 5% EuCPP scaffolds could significantly promote the migration and proliferation of bone marrow stromal cells which effectively promote angiogenesis; 5% EuCPP could significantly upregulate the ratio of OPG/RANKL in MC3T3-E1 and promote the secretion of osteogenic-related growth factors (ALP and OPN) from MC3T3-E1, indicating the potential of the scaffold to inhibit bone resorption and promote bone formation. In conclusion, 5% EuCPP possesses the biological properties of pro-angiogenesis, anti-inflammation, pro-osteogenesis, and inhibiting bone resorption, which may provide a sustained positive effect throughout the process of bone tissue repair.

Enhancing osteoblast differentiation and bone repair: The priming effect of photobiomodulation on adipose stromal cells

Cellular therapy using adipose tissue–derived mesenchymal stromal cells (at-MSCs) has garnered attention for the treatment of bone defects. Therefore, preconditioning strategies to enhance the osteogenic potential of at-MSCs could optimize cell therapy outcomes, and photobiomodulation (PBM) therapy has emerged as an effective, noninvasive, and low-cost alternative. This study explored the impacts of PBM on at-MSCs differentiation and the subsequent repair of bone defects treated with cell injection. Rat at-MSCs were cultured and irradiated (at-MSCsPBM) following the PBM protocol (660 nm; 20 mW; 0.714 W/cm2; 0.14 J; 5 J/cm2). Cellular differentiation was assessed based on the expression of gene and protein markers. Reactive oxygen species (ROS) were detected using fluorescence. At-MSCsPBM were injected into 5-mm calvarial lesions, and bone formation was analyzed using micro-CT and histological evaluations. At-MSCs were used as control. Data were analyzed using the ANOVA or t-test. At-MSCsPBM exhibited high levels of gene and protein runt-related transcription factor-2 (Runx2) and alkaline phosphatase (Alp) expression. PBM increased ALP activity and significantly reduced ROS levels. In addition, PBM increased the expression of Wnt pathway–associated genes. In vivo, there was an increase in the morphometric parameters, including bone volume, percentage of bone volume, bone surface area, and trabecular number, in at-MSCsPBM-treated defects compared with those in the control. These findings suggest that PBM enhances the osteogenic potential of at-MSCs, thereby supporting the advancement of improved cellular therapies for bone regeneration.