Transcriptomic profiling of human mesenchymal stem cells using a pulsed electromagnetic-wave motion bioreactor system for enhanced osteogenic commitment and therapeutic potentials.

Traditional bioreactor systems involve the use of three-dimensional (3D) scaffolds or stem cell aggregates, limiting the accessibility to the production of cell-secreted biomolecules. Herein, we present the use a pulse electromagnetic fields (pEMFs)-assisted wave-motion bioreactor system for the dynamic and scalable culture of human bone marrow-derived mesenchymal stem cells (hBMSCs) with enhanced the secretion of various soluble factors with massive therapeutic potential. The present study investigated the influence of dynamic pEMF (D-pEMF) on the kinetic of hBMSCs. A 30-min exposure of pEMF (10V-1Hz, 5.82 G) with 35 oscillations per minute (OPM) rocking speed can induce the proliferation (1 × 105 â†’ 4.5 × 105) of hBMSCs than static culture. Furthermore, the culture of hBMSCs in osteo-induction media revealed a greater enhancement of osteogenic transcription factors under the D-pEMF condition, suggesting that D-pEMF addition significantly boosted hBMSCs osteogenesis. Additionally, the RNA sequencing data revealed a significant shift in various osteogenic and signaling genes in the D-pEMF group, further suggesting their osteogenic capabilities. In this research, we demonstrated that the combined effect of wave and pEMF stimulation on hBMSCs allows rapid proliferation and induces osteogenic properties in the cells. Moreover, our study revealed that D-pEMF stimuli also induce ROS-scavenging properties in the cultured cells. This study also revealed a bioactive and cost-effective approach that enables the use of cells without using any expensive materials and avoids the possible risks associated with them post-implantation.

Stiff extracellular matrix drives the differentiation of mesenchymal stem cells toward osteogenesis by the multiscale 3D genome reorganization.

Extracellular matrix (ECM) stiffness is a major driver of stem cell fate. However, the involvement of the three-dimensional (3D) genomic reorganization in response to ECM stiffness remains unclear. Here, we generated comprehensive 3D chromatin landscapes of mesenchymal stem cells (MSCs) exposed to various ECM stiffness. We found that there were more long-range chromatin interactions, but less compartment A in MSCs cultured on stiff ECM than those cultured on soft ECM. However, the switch from compartment B in MSCs cultured on soft ECM to compartment A in MSCs cultured on stiff ECM included genes encoding proteins primarily enriched in cytoskeleton organization. At the topologically associating domains (TADs) level, stiff ECM tends to have merged TADs on soft ECM. These merged TADs on stiff ECM include upregulated genes encoding proteins enriched in osteogenesis, such as SP1, ETS1, and DCHS1, which were validated by quantitative real-time polymerase chain reaction and found to be consistent with the increase of alkaline phosphatase staining. Knockdown of SP1 or ETS1 led to the downregulation of osteogenic marker genes, including COL1A1, RUNX2, ALP, and OCN in MSCs cultured on stiff ECM. Our study provides an important insight into the stiff ECM-mediated promotion of MSC differentiation towards osteogenesis, emphasizing the influence of mechanical cues on the reorganization of 3D genome architecture and stem cell fate.

Cell-free bilayer functionalized scaffold for osteochondral tissue engineering.

Osteochondral tissue engineering using layered scaffolds is a promising approach for treating osteochondral defects as an alternative to microfracture procedure, autologous chondrocyte implantation, and cartilage-bone grafting. The team previously investigated the chondrogenesis of mesenchymal stem cells (MSCs) on a polycaprolactone (PCL)/acetylated hyaluronic acid scaffold. The present study first focused on fabricating a novel osteoconductive scaffold utilizing bismuth-nanohydroxyapatite/reduced graphene oxide (Bi-nHAp/rGO) nanocomposite and electrospun PCL. The osteoconductive ability of the scaffold was investigated by evaluating the alkaline phosphatase (ALP) activity and the osteogenic genes expression in the adipose-derived MSCs. The expression of Runx2, collagen I, ALP, and osteocalcin as well as the result of ALP activity indicated the osteoconductive potential of the Bi-nHA-rGO/PCL scaffold. In the next step, a bilayer scaffold containing Bi-nHAp/rGO/PCL as an osteogenic layer and acetylated hyaluronic acid/PCL as a chondrogenic layer was prepared by the electrospinning technique and transplanted into osteochondral defects of rats. The chondrogenic and osteogenic markers corresponding to the surrounding tissues of the transplanted scaffold were surveyed 60 days later by real-time polymerase chain reaction (PCR) and immunohistochemistry methods. The results showed increased chondrogenic (Sox9 and collagen II) and osteogenic (osteocalcin and ALP) gene expression and augmented secretion of collagens II and X after transplantation. The results strongly support the efficacy of this constructed cell-free bilayer scaffold to induce osteochondral defect regeneration.

Copper ions-photo dual-crosslinked alginate hydrogel for angiogenesis and osteogenesis.

Early healing of bone defects is still a clinical challenge. Many bone-filling materials have been studied, among which photocrosslinked alginate has received significant attention due to its good biocompatibility and morphological plasticity. Although it has been confirmed that photocrosslinked alginate can be used as an extracellular matrix for 3D cell culture, it lacks osteogenesis-related biological functions. This study constructed a copper ions-photo dual-crosslinked alginate hydrogel scaffold by controlling the copper ion concentration. The scaffolds were shaped by photocrosslinking and then endowed with biological functions by copper ions crosslinking. According to in vitro research, the dual-crosslinked hydrogel increased the compressive strength and favored copper dose-dependent osteoblast differentiation and cell surface adherence of rat bone marrow mesenchymal stem cells and the expression of type I collagen (Col1), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), vascular endothelial growth factor (VEGF). In addition, hydrogel scaffolds were implanted into rat skull defects, and more angiogenesis and osteogenesis could be observed in in vivo studies. The above results show that the copper-photo-crosslinked hydrogel scaffold has excellent osseointegration properties and can potentially promote angiogenesis and early healing of bone defects, providing a reference solution for bone tissue engineering materials.

Multifunctional Bionic Periosteum with Ion Sustained-Release for Bone Regeneration.

In this study, a novel bionic periosteum (BP)-bioactive glass fiber membrane (BGFM) is designed. The introduction of magnesium ion (Mg2+) and zinc ion (Zn2+) change the phase separation during the electrospinning (ES) jet stretching process. The fiber's pore structure transitions from connected to closed pores, resulting in a decrease in the rapid release of metal ions while also improving degradation via reducing filling quality. Additionally, the introduction of magnesium (Mg) and zinc (Zn) lead to the formation of negative charged tetrahedral units (MgO4 2- and ZnO4 2-) in the glass network. These units effectively trap positive charged metal ions, further inhibiting ion release. In vitro experiments reveal that the deigned bionic periosteum regulates the polarization of macrophages toward M2 type, thereby establishing a conducive immune environment for osteogenic differentiation. Bioinformatics analysis indicate that BP enhanced bone repair via the JAK-STAT signaling pathway. The slow release of metal ions from the bionic periosteum can directly enhance osteogenic differentiation and vascularization, thereby accelerating bone regeneration. Finally, the bionic periosteum exhibits remarkable capabilities in angiogenesis and osteogenesis, demonstrating its potential for bone repair in a rat calvarial defect model.

Dihydromyricetin-loaded oxidized polysaccharide/L-arginine chitosan adhesive hydrogel promotes bone regeneration by regulating PI3K/AKT signaling pathway and MAPK signaling pathway.

Bone defects caused by trauma, infection and congenital diseases still face great challenges. Dihydromyricetin (DHM) is a kind of flavone extracted from Ampelopsis grossedentata, a traditional Chinese medicine. DHM can enhance the osteogenic differentiation of human bone marrow mesenchymal stem cells with the potential to promote bone regeneration. Hydrogel can be used as a carrier of DHM to promote bone regeneration due to its unique biochemical characteristics and three-dimensional structure. In this study, oxidized phellinus igniarius polysaccharides (OP) and L-arginine chitosan (CA) are used to develop hydrogel. The pore size and gel strength of the hydrogel can be changed by adjusting the oxidation degree of oxidized phellinus igniarius polysaccharides. The addition of DHM further reduce the pore size of the hydrogel (213 µm), increase the mechanical properties of the hydrogel, and increase the antioxidant and antibacterial activities of the hydrogel. The scavenging rate of DPPH are 72.30 ± 0.33 %, and the inhibition rate of E.coli and S.aureus are 93.12 ± 0.38 % and 94.49 ± 1.57 %, respectively. In addition, PCAD has good adhesion and biocompatibility, and its extract can effectively promote the osteogenic differentiation of MC3T3-E1 cells. Network pharmacology and molecular docking show that the promoting effect of DHM on osteogenesis may be achieved by activating the PI3K/AKT and MAPK signaling pathways. This is confirmed through in vitro cell experiments and in vivo animal experiments.

Ultrasound-triggered piezoelectric polyetheretherketone with boosted osteogenesis via regulating Akt/GSK3ß/ß-catenin pathway.

Maxillofacial bone defects can severely impact quality of life by impairing physiological functions such as chewing, breathing, swallowing, and pronunciation. Polyether ether ketone (PEEK) is commonly used for the repair of maxillofacial defects due to its mechanical adaptability, while its osteogenic properties still need refinement. Herein, we have utilized the piezoelectric effect exhibited by barium titanate (BTO) under low-intensity pulsed ultrasound (LIPUS) to develop an ultrasound responsive PEEK (PDA@BTO-SPEEK, PBSP) through the mediating effect of polydopamine (PDA), for repairing maxillofacial bone defects. After modification by PDA@BTO, PBSP possesses better hydrophilicity, which is conducive to cell growth and adhesion. Simultaneously, by virtue of the piezoelectric characteristics of BTO, PBSP obtains a piezoelectric coefficient that matches the bone cortex. Notably, when PBSP is stimulated by LIPUS, it can generate stable electricity and effectively accelerate the osteogenic differentiation of osteoblasts through the regulation of the Piezo1-induced calcium (Ca2+) influx and Akt/GSK3ß/ß-catenin pathway. In addition, PBSP presents satisfactory therapeutic effects in rat skull defect models, and its osteogenic efficiency can be further improved under LIPUS stimulation with high tissue penetration. Collectively, PBSP + LIPUS exhibits great potential as a promising alternative strategy for the repair of maxillofacial bone defects.

Optimizing silicon doping levels for enhanced osteogenic and angiogenic properties of 3D-printed biphasic calcium phosphate scaffolds: An in vitro screening and in vivo validation study.

Biphasic calcium phosphate (BCP) ceramics are valued for their osteoconductive properties but have limited osteogenic and angiogenic activities, which restricts their clinical utility in bone defect repair. Silicon doping has emerged as an effective strategy to enhance these biological functions of BCP. However, the biological impact of BCP is influenced by the level of silicon doping, necessitating determination of the optimal concentration to maximize efficacy in bone repair. This study investigated the effects of silicon doping on both the physicochemical and biological properties of BCP, with a specific focus on osteogenic and angiogenic potentials. Results indicated that silicon doping exceeding 4 mol.% led to the formation of α-TCP, accelerating BCP degradation, enhancing silicon ion release, and promoting mineralization product formation. Simultaneously, silicon doping increased the porosity of BCP scaffolds, which typically reduces their compressive strength. Nevertheless, scaffolds doped with ≤4 mol.% silicon maintained compressive strengths exceeding 2 MPa. In vitro biological experiments indicated that higher levels of silicon doping (≥6 mol.%) partially inhibited the successful differentiation of stem cells and the vascularization of endothelial cells. Optimal conditions for promoting osteogenic differentiation and angiogenesis were identified between 2 and 4 mol.% silicon doping, with an optimal level of approximately 4 mol.%. Subsequent in vivo experiments confirmed that BCP scaffolds doped with 4 mol.% silicon effectively promoted vascularization and new bone formation, highlighting their potential for clinical bone defect repair.

A photothermal responsive system accelerating nitric oxide release to enhance bone repair by promoting osteogenesis and angiogenesis.

Managing bone defects remains a formidable clinical hurdle, primarily attributed to the inadequate orchestration of vascular reconstruction and osteogenic differentiation in both spatial and temporal dimensions. This challenge persists due to the constrained availability of autogenous grafts and the limited regenerative capacity of allogeneic or synthetic bone substitutes, thus necessitating continual exploration and innovation in the realm of functional and bioactive bone graft materials. While synthetic scaffolds have emerged as promising carriers for bone grafts, their efficacy is curtailed by deficiencies in vascularization and osteoinductive potential. Nitric oxide (NO) plays a key role in revascularization and bone tissue regeneration, yet studies related to the use of NO for the treatment of bone defects remain scarce. Herein, we present a pioneering approach leveraging a photothermal-responsive system to augment NO release. This system comprises macromolecular mPEG-P nanoparticles encapsulating indocyanine green (ICG) (NO-NPs@ICG) and a mPEG-PA-PP injectable thermosensitive hydrogel carrier. By harnessing the synergistic photothermal effects of near-infrared radiation and ICG, the system achieves sustained NO release, thereby activating the soluble guanylate cyclase (SGC)-cyclic guanosine monophosphate (cGMP) signaling pathway both in vitro and in vivo. This orchestrated cascade culminates in the facilitation of angiogenesis and osteogenesis, thus expediting the reparative processes in bone defects. In a nutshell, the NO release-responsive system elucidated in this study presents a pioneering avenue for refining the bone tissue microenvironment and fostering enhanced bone regeneration.

Enhancing bone regeneration: Unleashing the potential of magnetic nanoparticles in a microtissue model.

Bone tissue engineering addresses the limitations of autologous resources and the risk of allograft disease transmission in bone diseases. In this regard, engineered three-dimensional (3D) models emerge as biomimetic alternatives to natural tissues, replicating intracellular communication. Moreover, the unique properties of super-paramagnetic iron oxide nanoparticles (SPIONs) were shown to promote bone regeneration via enhanced osteogenesis and angiogenesis in bone models. This study aimed to investigate the effects of SPION on both osteogenesis and angiogenesis and characterized a co-culture of Human umbilical vein endothelial cells (HUVEC) and MG-63 cells as a model of bone microtissue. HUVECs: MG-63s with a ratio of 4:1 demonstrated the best results among other cell ratios, and 50 µg/mL of SPION was the optimum concentration for maximum survival, cell migration and mineralization. In addition, the data from gene expression illustrated that the expression of osteogenesis-related genes, including osteopontin, osteocalcin, alkaline phosphatase, and collagen-I, as well as the expression of the angiogenesis-related marker, CD-31, and the tube formation, is significantly elevated when the 50 µg/mL concentration of SPION is applied to the microtissue samples. SPION application in a designed 3D bone microtissue model involving a co-culture of osteoblast and endothelial cells resulted in increased expression of specific markers related to angiogenesis and osteogenesis. This includes the design of a novel biomimetic model to boost blood compatibility and biocompatibility of primary materials while promoting osteogenic activity in microtissue bone models. Moreover, this can improve interaction with surrounding tissues and broaden the knowledge to promote superior-performance implants, preventing device failure.

Strontium zinc silicate simultaneously alleviates osteoporosis and sarcopenia in tail-suspended rats via Piezo1-mediated Ca2+ signaling.

Background: Long-term physical inactivity probably leads to a co-existence of osteoporosis and sarcopenia which result in a high risk of falls, fractures, disability and even mortality. However, universally applicable and feasible approaches are lacking in the concurrent treatment of osteoporosis and sarcopenia. In this study, we evaluated the effect of strontium zinc silicate bioceramic (SZS) extract on osteoporosis and sarcopenia and explored its underlying mechanisms. Methods: Hindlimb osteoporosis and sarcopenia were established in a tail-suspended rat model. The bones were conducted µCT scanning, histological examination, and gene expression analysis, and the muscles were conducted histological examination and gene expression analysis. In vitro, the effect of SZS extract on osteoblasts was determined by alizarin red S staining, immunofluorescence and qPCR. Similarly, the effect of SZS extract on myoblasts was determined by immunofluorescence and qPCR.. At last, the role of Piezo1 and the change of intracellular calcium ion (Ca2+) were explored through blockading the Piezo1 by GsMTx4 in MC3T3-E1 and C2C12 cells, respectively. Results: We found that SZS extract could concurrently and efficiently prevent bone structure deterioration, muscle atrophy and fibrosis in hind limbs of the tail-suspended rats. The in vivo study also showed that SZS extract could upregulate the mRNA expression of Piezo1, thereby maintaining the homeostasis of bones and muscles. In vitro study demonstrated that SZS extract could promote the proliferation and differentiation of MC3T3-E1 and C2C12 cells by increasing the intracellular Ca2+ in a Piezo1-dependent manner. Conclusion: This study demonstrated that SZS extract could increase Piezo1-mediated intracellular Ca2+, and facilitate osteogenic differentiation of osteoblast and myogenic differentiation of myoblasts, contributing to alleviation of osteoporosis and sarcopenia in a tail-suspended rat model. The translational potential of this article: The current study might provide a universally applicable and efficient strategy to treat musculoskeletal disorders based on bioactive ceramics. The verification of the role of Piezo1-modulated intracellular Ca2+ during osteogenesis and myogenesis provided a possible therapeutic target against mechanical related diseases.

Multiple-Effect Combined Hydrogels: "Temporal Regulation" Treatment of Osteosarcoma-Associated Bone Defects with Switchable Hyperthermia and Bioactive Agents.

Achieving the clinically staged treatment of osteosarcoma-associated bone defects encounters the multiple challenges of promptly removing postoperative residual tumor cells and bacterial infection, followed by bone reconstruction. Herein, a core/shell hydrogel with multiple-effect combination is designed to first exert antitumor and antibacterial activities and then promote osteogenesis. Specifically, doxorubicin (DOX) is loaded by magnesium-iron-based layered double hydroxide (LDH) to prepare LDOX, which is introduced into a thermo-sensitive hydrogel to serve as an outer shell of the core/shell hydrogel, meanwhile, LDH-contained liquid crystal hydrogel, abbreviated as LCgel-L, is served as an inner core. At the early stage of treatment, the dissociation of the outer shell triggered by moderate hyperthermia led to the thermo-sensitive release of LDOX, which can be targeted for the release of DOX within tumor cells, thereby promptly removing postoperative residual tumor cells based on the synergistic effect of photothermal therapy (PTT) and DOX, and postoperative bacterial infection can also be effectively prevented by PTT simultaneously. More importantly, the dissociation of the outer shell prompted the full exposure of the inner core, which will exert osteogenic activity based on the synergy of liquid crystal hydrogel as well as LDH-induced mild hyperthermia and ion effects, thereby enabling "temporal regulation" treatment of osteosarcoma-associated bone defects. This study provides a valuable insight for the development of osteosarcoma-associated bone repair materials.

Transverse Distraction of Great Toe to Enlarge the Donor Site before Finger Reconstruction.

Partial great toe transfer is widely used in finger reconstruction. Although satisfactory results have been reported at the recipient's hand, the donor foot still presents with many problems due to the large amount of tissues harvested. In this study, the Ilizarov technique was utilized to enlarge the great toe in order to minimize the amount of tissue sacrificed of the donor foot. In this retrospective study, 23 patients (30 toes) underwent transverse distraction of the great toe for finger reconstruction from September 2020 to December 2022. The width of the contralateral normal finger was set as the objective width gained of distraction. At the last follow-up, the changes of bone, toenail, plantar skin, vessel, and nerve of the great toe were measured, and postoperative complications were assessed. The time for active distraction was 46.1 ± 8.3 days, with a widening rate of 0.41 ± 0.08 mm/day. Counting in the time for latency and consolidation, the time of treatment with external fixation was 84 ± 11.9 days. At the last follow-up, the average width of the distal phalanx of the great toe increased from 13.1 to 28.1 mm (p < 0.001). The width of the toenail increased from 15.8 to 30.3 mm (p < 0.001), and the width of the plantar pulp increased from 25.6 to 38.8 mm (p < 0.001). Computed tomography angiography (CTA) and Doppler ultrasound confirmed that the digital arteries and nerves of the great toe were intact after distraction surgery. Two patients needed revision surgery due to complications of pin loosening or premature consolidation. With the help of the Ilizarov technique, the great toe is effectively enlarged after transverse distraction. Multiple tissues of the great toe, including bone, nail, and plantar skin, are regenerated, and more tissues were preserved after toe-to-hand transfer. To the best of our knowledge, this is a novel method to enlarge the donor site for finger reconstruction.

Nanoarchitecture-Integrated Hydrogel Boosts Angiogenesis-Osteogenesis-Neurogenesis Tripling for Infected Bone Fracture Healing.

Infected fracture healing is a complicated process that includes intricate interactions at the cellular and molecular levels. In addition to angiogenesis and osteogenesis, the significance of neurogenesis in fracture healing has also been recognized in recent years. Here, a nanocomposite hydrogel containing pH-responsive zinc-gallium-humic acids (HAs) nanoparticles is developed. Through the timed release of Zn2+, Ga3+, and HAs, the hydrogel exhibits potent antibacterial effects and promotes angiogenesis, osteogenesis, and neurogenesis. The enhanced neurogenesis further promotes angiogenesis and osteogenesis, forming a mutually supportive angiogenesis-osteogenesis-neurogenesis cycle at the fracture site. The hydrogel achieves rapid infected fracture healing and improves tissue regeneration in mice. This study proposes a comprehensive treatment approach that combines antibacterial effects with the regulation of tissue regeneration to improve infected fracture healing.

Potential plausible role of Wharton's jelly mesenchymal stem cells for diabetic bone regeneration.

This letter addresses the review titled "Wharton's jelly mesenchymal stem cells: Future regenerative medicine for clinical applications in mitigation of radiation injury". The review highlights the regenerative potential of Wharton's jelly mesenchymal stem cells (WJ-MSCs) and describes why WJ-MSCs will become one of the most probable stem cells for future regenerative medicine. The potential plausible role of WJ-MSCs for diabetic bone regeneration should be noticeable, which will provide a new strategy for improving bone regeneration under diabetic conditions.

Meticulously engineered three-dimensional-printed scaffold with microarchitecture and controlled peptide release for enhanced bone regeneration.

The repair of large load-bearing bone defects requires superior mechanical strength, a feat that a single hydrogel scaffold cannot achieve. The objective is to seamlessly integrate optimal microarchitecture, mechanical robustness, vascularisation, and osteoinductive biological responses to effectively address these critical load-bearing bone defects. To confront this challenge, three-dimensional (3D) printing technology was employed to prepare a polycaprolactone (PCL)-based integrated scaffold. Within the voids of 3D printed PCL scaffold, a methacrylate gelatin (GelMA)/methacrylated silk fibroin (SFMA) composite hydrogel incorporated with parathyroid hormone (PTH) peptide-loaded mesoporous silica nanoparticles (PTH@MSNs) was embedded, evolving into a porous PTH@MSNs/GelMA/SFMA/PCL (PM@GS/PCL) scaffold. The feasibility of fabricating this functional scaffold with a customised hierarchical structure was confirmed through meticulous chemical and physical characterisation. Compression testing unveiled an impressive strength of 17.81 ± 0.83 MPa for the composite scaffold. Additionally, in vitro angiogenesis potential of PM@GS/PCL scaffold was evaluated through Transwell and tube formation assays using human umbilical vein endothelium, revealing the superior cell migration and tube network formation. The alizarin red and alkaline phosphatase staining assays using bone marrow-derived mesenchymal stem cells clearly illustrated robust osteogenic differentiation properties within this scaffold. Furthermore, the bone repair potential of the scaffold was investigated on a rat femoral defect model using micro-computed tomography and histological examination, demonstrating enhanced osteogenic and angiogenic performance. This study presents a promising strategy for fabricating a microenvironment-matched composite scaffold for bone tissue engineering, providing a potential solution for effective bone defect repair.

Injectable dual drug-loaded thermosensitive liposome-hydrogel composite scaffold for vascularised and innervated bone regeneration.

Adequate blood supply and thorough innervation are essential to the survival of tissue-engineered bones. Though great progress has been created in the application of bone tissue engineering technology to bone defect repair, many challenges remain, such as insufficient vascularisation and deficient innervation in newly regenerated bone. In the present study, we addressed these challenges by manipulating the bone regeneration microenvironment in terms of vascularisation and innervation. We used a novel injectable thermosensitive liposome-hydrogel composite scaffold as a sustained-release carrier for basic fibroblast growth factor (bFGF, which promotes angiogenesis and neurogenic differentiation) and dexamethasone (Dex, which promotes osteogenic differentiation). In vitro biological assessment demonstrated that the composite scaffold had sufficient cell compatibility; it enhanced the capacity for angiogenesis in human umbilical vein endothelial cells, and the capacity for neurogenic/osteogenic differentiation in human bone marrow mesenchymal stem cells. Moreover, the introduction of bFGF/Dex liposome-hydrogel composite scaffold to bone defect sites significantly improved vascularisation and innervated bone regeneration properties in a rabbit cranial defect model. Based on our findings, the regeneration of sufficiently vascularised and innervated bone tissue through a sustained-release scaffold with excellent injectability and body temperature sensitivity represents a promising tactic towards bone defect repair.

Bone Quality and Mineralization and Effects of Treatment in Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a rare congenital bone dysplasia characterized by high fracture rates and broad variations in clinical manifestations ranging from mild to increasingly severe and perinatal lethal forms. The underlying mutations affect either the synthesis or processing of the type I procollagen molecule itself or proteins that are involved in the formation and mineralization of the collagen matrix. Consequently, the collagen forming cells, the osteoblasts, become broadly dysfunctional in OI. Strikingly, hypermineralized bone matrix seems to be a frequent feature in OI, despite the variability in clinical severity and mutations in the so far studied different forms of human OI. While the causes of the increased mineral content of the bone matrix are not fully understood yet, there is evidence that the descendants of the osteoblasts, the osteocytes, which play a critical role not only in bone remodeling, but also in mineralization and sensing of mechanical loads, are also highly dysregulated and might be of major importance in the pathogenesis of OI. In this review article, we firstly summarize findings of cellular abnormalities in osteoblasts and osteocytes, alterations of the organic matrix, as well as of the microstructural organization of bone. Secondly, we focus on the hypermineralization of the bone matrix in OI as observed in several different forms of human OI as well as in animal models, its measurement and potential mechanical implications and its effect on the bone mineral density measured by dual X-ray absorptiometry. Thirdly, we give an overview of established medication treatments of OI and new approaches with a focus of their known or possible effects on the bone material, particularly on bone matrix mineralization.

The effect of compressive force in bone tissue induced by implants of different primary stabilities on macrophage polarization and bone regeneration.

Dental implants with different primary stabilities give rise to distinct stress distributions at the implant-bone interface after placement and exert mechanical force on the cells in the bone tissue. This study aimed to investigate whether the mechanical forces in peri-implant bone participate in the body's immune response and influence macrophage polarization. Therefore, an in vivo rat implantation model with different primary implant stabilities was established. The osteoimmune response and macrophage polarization were investigated, and the osseointegration of the implants was evaluated. In an in vitro experiment, an external compressive force was applied to RAW264.7 cells, and the polarization phenotype was observed. MC3T3-E1 cells were cultured in macrophage-conditioned medium to investigate the regulatory effect of the macrophage-secreted cytokines on the osteogenic differentiation of osteoblasts. In vivo experimental results indicated that the primary stability of implants is positively correlated with the mechanical force. The osteoimmune response was significantly amplified by compressive force generated from implants. This compressive force first induced both M1 and M2 macrophage polarization and then accelerated the progression of the transition to M2 macrophages in the bone repair phase. In vitro, compressive force significantly upregulated the M1 and M2 macrophage polarization. In addition, the suppressive effect of macrophages on the osteogenesis of MC3T3 cells was relieved by cytokines secreted by macrophages under compressive force loading, which promoted their osteogenesis. Overall, these results clarify that compressive force from different primary stabilities is an important influencing factor regulating the osteoimmunne response and macrophage polarization in addition to maintaining the implant.

A Successful Laparoscopic Appendectomy for an Adult Male Patient with Osteogenesis Imperfecta.

Background: Osteogenesis imperfecta (OI) is a genetic connective tissue disease defined by the loss of bone mass and density, which makes the bones more brittle and more likely to fracture over time. Bone deformity and articular instability are the subsequent symptoms. Case report: This 25-year-old man had malformed lower limbs and trouble walking due to OI and dwarfism. He arrived complaining of fever, nausea, vomiting and diffuse peri-umbilical pain. During ultrasonography a blinded, oedematous lobe formation containing an appendicolith was discovered. Acute suppurative appendicitis was diagnosed, necessitating a laparoscopic appendectomy. Because the patient had previously undergone general anaesthesia, anaesthesia was thought to be attainable. Pneumoperitoneum and a 10 mm optical port inserted into the umbilicus were used in the surgical procedure. A diagnostic laparoscopy revealed faecolith obstruction and an acute suppurative appendicitis. After an hour, a laparoscopic appendectomy was performed effectively with little blood loss. Without experiencing any difficulties because of the surgery position, the patient was discharged. Conclusion: We present a case of an OI dwarf patient with acute suppurative appendicitis. It highlights the possibility of performing laparoscopic surgery in general and a laparoscopic appendectomy in particular on OI patients. LEARNING POINTS: In rare instances involving OI, laparoscopic surgery in general and laparoscopic appendectomy in particular are practical and efficient options.