Bone Regeneration In Defects Research Articles

Influence of bisphosphonate treatment on bone substitute performance in osteoporotic conditions.

Considering the elevated number of osteoporotic patients in need of bone graft procedures, we here evaluated the effect of alendronate (ALN) treatment on the regeneration of bone defects in osteoporotic rats. Bone formation was histologically and histomorphometrically assessed in rat femoral condyle bone defects filled with bone graft (Bio-Oss®) or left empty. Male Wistar rats were induced osteoporotic through orchidectomy (ORX) and SHAM-operated. The animals were divided into three groups: osteoporotic (ORX), osteoporotic treated with ALN (ORX + ALN) and healthy (SHAM). Six weeks after ORX or SHAM surgeries, bone defects were created bilaterally in femoral condyles; one defect was filled with Bio-Oss® and the other one left empty. Bone regeneration within the defects was analyzed by histology and histomorphometry after 4 and 12 weeks. Histological samples showed new bone surrounding Bio-Oss® particles from week 4 onward in all three groups. At week 12, the data further showed that ALN treatment of osteoporotic animals enhanced bone formation to a 10-fold increase compared to non-treated osteoporotic control. Bio-Oss® filling of the defects promoted bone formation at both implantation periods compared to empty controls. Our histological and histomorphometric results demonstrate that the enteral administration of alendronate under osteoporotic bone conditions leverages bone defect regeneration to a level comparable to that in healthy bone. Additionally, Bio-Oss® is an effective bone substitute, increasing bone formation, and acting as an osteoconductive scaffold guiding bone growth in both healthy and osteoporotic bone conditions. Based on the results of this study, enteral use of ALN mitigates adverse effects of an osteoporotic condition on bone defect regeneration.

Harnessing Nucleic Acids Nanotechnology for Bone/Cartilage Regeneration.

The effective regeneration of weight-bearing bone defects and critical-sized cartilage defects remains a significant clinical challenge. Traditional treatments such as autologous and allograft bone grafting have not been successful in achieving the desired outcomes, necessitating the need for innovative therapeutic approaches. Nucleic acids have attracted significant attention due to their ability to be designed to form discrete structures and programmed to perform specific functions at the nanoscale. The advantages of nucleic acid nanotechnology offer numerous opportunities for in-cell and in vivo applications, and hold great promise for advancing the field of biomaterials. In this review, the current abilities of nucleic acid nanotechnology to be applied in bone and cartilage regeneration are summarized and insights into the challenges and future directions for the development of this technology are provided.

Research landscape of 3D printing in bone regeneration and bone repair: A bibliometric and visualized analysis from 2012 to 2022.

Three-dimensional printing (3DP) is a popular manufacturing technique with versatile potential for materials processing in tissue engineering and regenerative medicine. In particular, the repair and regeneration of significant bone defects remain as substantial clinical challenges that require biomaterial implants to maintain mechanical strength and porosity, which may be realized using 3DP. The rapid progress in 3DP development in the past decade warrants a bibliometric analysis to gain insights into its applications in bone tissue engineering (BTE). Here, we performed a comparative study using bibliometric methods for 3DP in bone repair and regeneration. A total of 2,025 articles were included, and the results showed an increase in the number of publications and relative research interest on 3DP annually worldwide. China was the leader in international cooperation in this field and also the largest contributor to the number of citations. The majority of articles in this field were published in the journal Biofabrication. Chen Y was the author who made the highest contribution to the included studies. The keywords included in the publications were mainly related to BTE and regenerative medicine (including "3DP techniques," "3DP materials," "bone regeneration strategies," and "bone disease therapeutics") for bone regeneration and repair. This bibliometric and visualized analysis provides significant insights into the historical development of 3DP in BTE from 2012 to 2022, which will be beneficial for scientists to conduct further investigations into this dynamic field.

The study of self-regulating α-TCP based composite by micro/nano scaled silk fibroin and α-CSH on physicochemical and biological properties of bone cement.

A novel self-hardening α-tricalcium phosphate (α-TCP) bone cement complexed with different content of α-calcium sulfate hemihydrate (α-CSH) and micrometer hydroxyapatite mineralized silk fibroin (HA-SF) using micro/SF as curing liquid has been investigated in this work, which was capable of tunable setting time, degradation, mechanical property and ability to anti-washout. After addition 0 ∼ 25% α-CSH to the α-TCP cement with SFFs as curing liquid, it shortened the setting time of the modified composite to 10 ∼ 30min. Furthermore, the addition of SFFs improved the compressive strength of the composite from 5.41MPa to 9.44MPa. The composites with both Na2HPO4 and SFFs as curing liquid showed good anti-collapse performance. The weight loss ratio of bone cement was -0.18 ∼ 12.08% in 4weeks when the content of α-CSH in α-TCP/α-CSH was between 0 ∼ 25wt%. During the degradation of α-CSH, the amorphous α-TCP were deposited as hydroxyapatite to formed a plate-like products on the surface of composite. Compared to the composite with Na2HPO4 solution as the curing liquid, alkaline phosphatase (ALP) activity of the composites using SFFs as curing liquid were maintained at high levels on the 14th day especially when the Ca/P ratio was 1.7. This study provides a theoretical basis for the regeneration of bone defects guided by bone cement materials.

Dual-functional borosilicate glass (BSG) delivery implant for osteomyelitis treatment and bone regeneration

Effective treatment of osteomyelitis remains to be clinical challenge due to the recurrent and persistent nature of the disease. Studies have shown that borate glasses can serve as implants for local drug delivery in treating osteomyelitis, as well as aid in regenerating bone defects in vivo. However, both the kinetics of drug release from borate glass-based implants and the underlying molecular mechanism for promoting bone regeneration remain unclear. Here, delivery implants with varying amounts of antibiotics were fabricated by encapsulating gentamicin sulfate (GS) into a chitosan glue and applying it to borosilicate glass (BSG). Upon immersion in phosphate buffered saline (PBS), delivery implants degraded and converted into hydroxyapatite (HA). All delivery implants released GS sustainably over a period of around 25 days in both PBS and K2HPO4 solutions and displayed efficacious inhibition of E. coli and S. aureus in vitro. GS release occurred through diffusion for inhibition whereby Fickian diffusion was revealed to be the predominant release kinetic. Ions (B, Ca, P and Si) released from BSG supported the proliferation, differentiation, osteogenic gene expression and protein secretion of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. When implanted in a rabbit tibial osteomyelitis model, osteomyelitis in the experimental group with delivery implants was effectively cured. Meanwhile, delivery implants have significant osteogenesis-promoting effects after implantation time of 12-weeks in vivo. Implantation of BSG-based drug delivery implants developed in this study may provide a promising method for treating osteomyelitis as well as for facilitating efficient bone regeneration.

3D-printed dual-ion chronological release functional platform reconstructs neuro-vascularization network for critical-sized bone defect regeneration

Critical-sized bone defects remain an unsolved challenge because of the failure to induce early reconstruction of the neuro-vascularization network. Nerve and vascular regeneration begin immediately after the occurrence of bone defect and play a key role in the subsequent osteogenic differentiation. In this study, a 3D-printed alpha-tricalcium phosphate scaffolds with dual-ion chronological release functional platform consisted of magnesium containing gelatin microspheres and zinc-doped bioglass was designed to reconstruct neuro-vascularization network for critical-sized bone defect regeneration. Our results demonstrated that magnesium containing gelatin microspheres could regulate the release rate of Mg2+ and achieve early complete release of Mg2+. The controlled release of Mg2+ can effectively enhance the vascularization of human umbilical vein endothelial cells and the ability of nerve regeneration of PC12 cells in vitro and also avoid the potential inhibition of high concentration of Mg2+ on bone formation in late osteogenesis. Moreover, zinc-doped bioglass ensured the long-term release of Zn2+, thereby promoting the activity and osteogenic differentiation of bone marrow mesenchymal stem cells. In rat calvarial critical-sized defect models, 3D-printed alpha-tricalcium phosphate scaffolds with dual-ion chronological release functional platform could significantly enhance neuro-vascularization network density and exhibited excellent performance in promoting new bone formation. Consequently, the 3D-printed alpha-tricalcium phosphate scaffolds with dual-ion chronological release functional platform has the potential to be used as bone grafts for repairing critical-sized bone defects and provides guidance for the design of repair materials.

Strontium Ion-Functionalized Nano-Hydroxyapatite/Chitosan Composite Microspheres Promote Osteogenesis and Angiogenesis for Bone Regeneration

Critical-size bone defects are an important problem in clinical practice, which usually occurs in severe trauma, or tumor resection, and cannot heal completely and autonomously. Implantation of grafts is often required to promote the regeneration of critical-size bone defects. Metal ions play an important role in human health, as they affect the body's metabolism and the tissue function. Strontium ions (Sr2+) can promote osteogenesis and angiogenesis. Herein, we prepared nano-hydroxyapatite (nHA)/chitosan (CS) composite microspheres with a uniform particle size distribution and an extracellular matrix-like nanofiber structure using microfluidic technology and direct alkali-induced gelation. Strontium ions were stably added into the microspheres by using polydopamine (PDA) to chelate metal ions forming a bone repair material (nHA/CS@PDA-Sr) with good bioactivity. The coordination reaction of PDA can effectively control the release of strontium ions and avoid the negative effects caused by the high strontium concentration. Our in vitro experiments showed that the composite microspheres had good biocompatibility and that the PDA coating promotes cell adhesion. The slow release of strontium ions can effectively promote mesenchymal stem cells osteogenic differentiation and the vascularization of endothelial cells. In addition, we injected composite microspheres into cranial defects of rats to evaluate osseointegration in vivo. The results showed that nHA/CS@PDA-Sr could effectively promote bone regeneration in the defect area. This study demonstrates that composite microspheres stimulate bone repair providing a promising way for bone-defect regeneration.

ENGINEERED EXTRACELLULAR MATRIX ENHANCES THE BONE REGENERATION POTENTIAL OF AGED HUMAN BONE MARROW STROMAL CELLS

Regeneration of bone defects in elderly patients is limited due to the decreased function of bone forming cells and compromised tissue physiology. Previous studies suggested that the regenerative activity of stem cells from aged tissues can be enhanced by exposure to young systemic and tissue microenvironments. The aim of our project was to investigate whether extracellular matrix (ECM) engineered from human induced pluripotent stem cells (hiPSCs) can enhance the bone regeneration potential of aged human bone marrow stromal cells (hBMSCs).ECM was engineered from hiPSC-derived mesenchymal-like progenitors (hiPSC-MPs), as well as young (<30 years) and aged (>70 years) hBMSCs. ECM structure and composition were characterized before and after decellularization using immunofluorescence and biochemical assays. Three hBMSCs of different ages were cultured on engineered ECMs. Growth and differentiation responses were compared to tissue culture plastic, as well as to collagen and fibronectin coated plates.Decellularized ECMs contained collagens type I and IV, fibronectin, laminin and < 5% residual DNA, suggesting efficient cell elimination. Cultivation of young and aged hBMSCs on the hiPSC-ECM in osteogenic medium significantly increased hBMSC growth and markers of osteogenesis, including collagen deposition, alkaline phosphatase activity, bone sialoprotein expression and matrix mineralization compared to plastic controls and single protein substrates. In aged BMSCs, matrix mineralization was only detected in ECM cultures in osteogenic medium. Comparison of ECMs engineered from hiPSC-MPs and hBMSCs of different ages suggested similar structure, composition and potential to enhance osteogenic responses in aged BMSCs. Engineered ECM induced a higher osteogenic response compared to specific matrix components.Our studies suggest that aged BMSCs osteogenic activity can be enhanced by culture on engineered ECM. hiPSCs represent a scalable cell source, and tissue engineering strategies employing engineered ECM materials could potentially enhance bone regeneration in elderly patients.

Strategy to improve endogenous bone regeneration of 3D-printed PCL/nano-HA composite scaffold: Collagen designs with BMP-2 and FGF-2

In bone tissue engineering, the endogenous regeneration of bone defects still represents a clinical challenge despite the development of intervention therapy to achieve bone regeneration via autologous grafts, allogeneic grafts, bone morphogenetic protein (BMP)-2, etc. To overcome the limitation of endogenous bone regeneration, we assumed that the 3D-printed collagen pattern with BMP-2 and fibroblast growth factor (FGF)-2 in the 3D-printed polycaprolactone/nano-hydroxyapatite scaffold could guide the endogenous regeneration of bone defects. Therefore, to test our hypothesis, polycaprolactone/nano-hydroxyapatite/collagen scaffolds with dual growth factors (BMP-2 and FGF-2) and various hydrogel patterns (positive, edge, and radial patterns) were fabricated at the same ratio and concentration of dual growth factors. Consequently, we revealed that the in vitro released concentrations of BMP-2 and FGF-2 were not affected by collagen patterns in the polycaprolactone/nano-hydroxyapatite scaffold. Furthermore, endogenous bone regeneration and angiogenesis in the polycaprolactone/nano-hydroxyapatite/collagen scaffold with a radial pattern were promoted compared with those in the polycaprolactone/nano-hydroxyapatite/collagen scaffolds with positive and edge patterns. Therefore, we demonstrated that a collagen design loaded with dual growth factors in the 3D-printed scaffold could affect endogenous bone regeneration and angiogenesis.

Effect of Bone Morphogenetic Protein–2 Combined With Microfracture for Osteochondral Defect of the Talus in a Rabbit Model

Background: Osteochondral defects of the talus can be effectively treated using microfracture, which is technically safe, accessible, and affordable. However, fibrous tissue and fibrocartilage comprise the majority of tissue repairs resulting from these procedures. These tissue types lack the mechanical characteristics of native hyaline cartilage and might significantly contribute to the decline in long-term outcomes. Recombinant human-bone morphogenetic protein–2 (rhBMP-2) has been shown to promote matrix synthesis and increase cartilage formation, thus enhancing chondrogenesis in vitro. Purpose: This study aimed to evaluate the treatment ability of combining rhBMP-2 with microfracture in rabbit talus osteochondral defect. Study Design: Controlled laboratory study. Methods: A full-thickness chondral defect (3 × 3 × 2 mm) was constructed in the center talar dome of 24 New Zealand White male rabbits, which were then divided into 4 groups of 6. Each group received the appropriate treatment: group 1 (control; no treatment of defect), group 2 (microfracture treatment), group 3 (rhBMP-2/hydroxyapatite treatment), and group 4 (microfracture combined with rhBMP-2/hydroxyapatite treatment). Animals were sacrificed at 2, 4, and 6 weeks postoperatively. The International Cartilage Regeneration & Joint Preservation Society macroscopic score, which considers the degree of defect repair, the integration to the border zone, and the macroscopic appearance, was used to assess the repaired tissue’s macroscopic appearance. Subchondral bone regeneration in defects was analyzed using micro–computed tomography, and the histological findings were graded using a modified version of the Wakitani scoring system for osteochondral repair. Results: At 2, 4, and 6 weeks, micro-computed tomography analysis revealed that groups 3 and 4 exhibited subchondral bone healing that was more significantly improved compared with groups 1. No sample showed excessive bone growth from the subchondral bone area. According to macroscopic and histological results, group 4 showed higher-quality cartilage and more accelerated cartilage regeneration than the other groups over time. Conclusion: These findings show that osteochondral defect repair in a rabbit talus model could be effectively accelerated and improved by combining rhBMP-2 with microfracture. Clinical Relevance: Using rhBMP-2 in combination with microfracture may enhance the repair of talar osteochondral lesions.

Repair of critical-sized bone defects in rabbit femurs using graphitic carbon nitride (g-C3N4) and graphene oxide (GO) nanomaterials

Various biomaterials have been evaluated to enhance bone formation in critical-sized bone defects; however, the ideal scaffold is still missing. The objective of this study was to investigate the in vitro and in vivo regenerative capacity of graphitic carbon nitride (g-C3N4) and graphene oxide (GO) nanomaterials to stimulate critical-sized bone defect regeneration. The in vitro cytotoxicity and hemocompatibility of g-C3N4 and GO were evaluated, and their potential to induce the in vitro osteogenesis of human fetal osteoblast (hFOB) cells was assessed using qPCR. Then, bone defect in femoral condyles was created in rabbits and left empty as control or filled with either g-C3N4 or GO. The osteogenesis of the different implanted scaffolds was evaluated after 4, 8, and 12 weeks of surgery using X-ray, computed tomography (CT), macro/microscopic examinations, and qPCR analysis of osteocalcin (OC) and osteopontin (OP) expressions. Both materials displayed good cell viability and hemocompatibility with enhanced collagen type-I (Col-I), OC, and OP expressions of the hFOB cells. Compared to the control group, the bone healing process in g-C3N4 and GO groups was promoted in vivo. Moreover, complete healing of the bone defect was observed radiologically and grossly in g-C3N4 implanted group. Additionally, g-C3N4 implanted group showed higher percentages of osteoid tissue, mature collagen, biodegradation, and expressions of OC and OP. In conclusion, our results revealed that g-C3N4 and GO nanomaterials could induce osteogenesis in critical-sized bone defects.

Sustained delivery of IL-10 by self-assembling peptide hydrogel to reprogram macrophages and promote diabetic alveolar bone defect healing.

Delayed regeneration of alveolar bone defects because of prolonged inflammation under diabetic conditions remains a challenge for dental rehabilitation in clinic, and effective therapies are required. Cytokines-based immuotherapies might be a potential strategy to regulate inflammation and bone regeneration. Here, we report that local delivery of interleukin-10 (IL-10) by injectable self-assembling peptide (SAP) hydrogel is efficient to promote proinflammatory (M1)-to-anti-inflammatory (M2) phenotype conversion, thereby enhancing bone regeneration in diabetic alveolar bone defects. Characteristics of SAP hydrogel were evaluated by morphology, injectable and rheological properties. The loading and release of IL-10 from the SAP hydrogel were evaluated over time in culture. The local inflammatory response and bone repair efficacy of the SAP/IL-10 hydrogel was evaluated in vivo using an alveolar bone defect model of diabetic mice. Finally, the direct effects of M2 macrophage on M1 phenotype and mineralization of MSCs were investigated. In vitro, encapsulated IL-10 could be sustainedly released by SAP hydrogel with preserved bioactivities. In vivo, SAP/IL-10 hydrogel showed significantly higher efficacy to attenuate M1 polarization and proinflammatory factors levels, and enhance expressions of osteogenic factors. As a result, diabetic bone regeneration induced by SAP/IL-10 hydrogel was significantly faster. Mechanistically, M2 macrophages induced by sustained IL-10 delivery might promote diabetic bone regeneration by reprogramming M1 phenotype, suppressing local inflammation and enhancing the osteogenic differentiation of mesenchymal stem cells (MSCs). This study highlights that the SAP hydrogel is a promising drug delivery platform for treatment of alveolar bone defects, which might have translational potential in future clinical applications.

Assessment of rhBMP-2-loaded bovine hydroxyapatite granules in the guided bone regeneration of critical bone defect in rat mandible bone

Assessment of rhBMP-2-loaded bovine hydroxyapatite granules in the guided bone regeneration of critical bone defect in rat mandible bone

Fabrication of Interleukin-4 Encapsulated Bioactive Microdroplets for Regulating Inflammation and Promoting Osteogenesis.

Despite the inherent regenerative ability of bone, large bone defect regeneration remains a major clinical challenge for orthopedic surgery. Therapeutic strategies medicated by M2 phenotypic macrophages or M2 macrophage inducer have been widely used to promote tissue remodeling. In this study, ultrasound-responsive bioactive microdroplets (MDs) encapsulated with bioactive molecule interleukin-4 (IL4, hereafter designated MDs-IL4) were fabricated to regulate macrophage polarization and potentiate the osteogenic differentiation of human mesenchymal stem cells (hBMSCs). The MTT assay, live and dead staining, and phalloidin/DAPI dual staining were used to evaluate biocompatibility in vitro. H&E staining was used to evaluate biocompatibility in vivo. Inflammatory macrophages were further induced via lipopolysaccharide (LPS) stimulation to mimic the pro-inflammatory condition. The immunoregulatory role of the MDs-IL4 was tested via macrophage phenotypic marker gene expression, pro-inflammatory cytokine level, cell morphological analysis, and immunofluorescence staining, etc. The immune-osteogenic response of hBMSCs via macrophages and hBMSCs interactions was further investigated in vitro. The bioactive MDs-IL4 scaffold showed good cytocompatibility in RAW 264.7 macrophages and hBMSCs. The results confirmed that the bioactive MDs-IL4 scaffold could reduce inflammatory phenotypic macrophages, as evidenced by changing in morphological features, reduction in pro-inflammatory marker gene expression, increase of M2 phenotypic marker genes, and inhibition of pro-inflammatory cytokine secretion. Additionally, our results indicate that the bioactive MDs-IL4 could significantly enhance the osteogenic differentiation of hBMSCs via its potential immunomodulatory properties. Our results demonstrate that the bioactive MDs-IL4 scaffold could be used as novel carrier system for other pro-osteogenic molecules, thus having potential applications in bone tissue regeneration.

3D Biomimetic Calcified Cartilaginous Callus that Induces Type H Vessels Formation and Osteoclastogenesis.

The formation of a calcified cartilaginous callus (CACC) is crucial during bone repair. CACC can stimulate the invasion of type H vessels into the callus to couple angiogenesis and osteogenesis, induce osteoclastogenesis to resorb the calcified matrix, and promote osteoclast secretion of factors to enhance osteogenesis, ultimately achieving the replacement of cartilage with bone. In this study, a porous polycaprolactone/hydroxyapatite-iminodiacetic acid-deferoxamine (PCL/HA-SF-DFO) 3D biomimetic CACC is developed using 3D printing. The porous structure can mimic the pores formed by the matrix metalloproteinase degradation of the cartilaginous matrix, HA-containing PCL can mimic the calcified cartilaginous matrix, and SF anchors DFO onto HA for the slow release of DFO. The in vitro results show that the scaffoldsignificantly enhances angiogenesis, promotes osteoclastogenesis and resorption by osteoclasts, and enhances the osteogenic differentiation of bone marrow stromal stem cells by promoting collagen triple helix repeat-containing 1 expression by osteoclasts. The in vivo results show that the scaffold significantly promotes type H vessels formation and the expression of coupling factors to promote osteogenesis, ultimately enhancing the regeneration of large-segment bone defects in rats and preventing dislodging of the internal fixation screw. In conclusion, the scaffold inspired by biological bone repair processes effectively promotes bone regeneration.

Additively manufactured MAX- and MXene-composite scaffolds for bone regeneration- recent advances and future perspectives

Human bones can suffer from various injuries, such as fractures, bone cancer, among others, which has initiated research activities towards bone replacement using advanced bio-materials. However, it is still challenging to design bio-scaffolds with bone-inducing agents to regenerate bone defects. In this regard, MAX-phases and MXenes (early transition metal carbides and/or nitrides) have gained notable attention due to their unique hydrophilicity, bio-compatibility, chemical stability, and photothermal properties. They can be used in bone tissue engineering as a suitable replacement or reinforcement for common bio-materials (polymers, bio-glasses, metals, or hydroxyapatite). To fabricate bio-scaffolds, additive manufacturing is prospective due to the possibility of controlling porosity and creating complex shapes with high resolution. Until now, no comprehensive article summarizing the existing state-of-the-art related to bone scaffolds reinforced by MAX-phases and MXenes fabricated by additive manufacturing has been published. Therefore, our article addresses the reasons for using bone scaffolds and the importance of choosing the most suitable material. We critically discuss the recent developments in bone tissue engineering and regenerative medicine using MAX-phases and MXenes with a particular emphasis on manufacturing, mechanical properties, and bio-compatibility. Finally, we discuss the existing challenges and bottlenecks of bio-scaffolds reinforced by MAX-phases and MXenes before deriving their future potential.

Improving Bone Formation by Guided Bone Regeneration Using a Collagen Membrane with rhBMP-2: A Novel Concept.

We examined whether recombinant human bone morphogenetic protein-2 (rhBMP-2) when applied to collagen membranes, would reinforce them during guided bone regeneration. Four critical cranial bone defects were created and treated in 30 New Zealand white rabbits, including a control group, critical defect only; group 1, collagen membrane only; group 2, biphasic calcium phosphate (BCP) only; group 3, collagen membrane + BCP; group 4, collagen membrane with rhBMP-2 (1.0 mg/mL); group 5, collagen membrane with rhBMP-2 (0.5 mg/mL); group 6, collagen membrane with rhBMP-2 (1.0 mg/mL) + BCP; and group 7, collagen membrane with rhBMP-2 (0.5 mg/mL) + BCP. After a 2-, 4-, or 8-week healing period, the animals were sacrificed. The combination of collagen membranes with rhBMP-2 and BCP yielded significantly higher bone formation rates compared to the other groups (control group and groups 1-5 < groups 6 and 7; p < 0.05). A 2-week healing period yielded significantly lower bone formation than that at 4 and 8 weeks (2 < 4 = 8 weeks; p < 0.05). This study proposes a novel GBR concept in which rhBMP-2 is applied to collagen membranes outside instead of inside the grafted area, thereby inducing quantitatively and qualitatively enhanced bone regeneration in critical bone defects.

Bovine Serum Albumin-Coated Ceria Nanoparticles Activate the TGF-β Signaling Pathway for Periodontal Bone Regeneration

Heterogeneous human periodontal ligament cells (hPDLCs) are the key seed cells to address the regeneration of periodontal bone defects, and nanomaterials b ring strategies for periodontal bone regeneration. Herein, we synthesized cerium-based nanoparticles by a convenient, green, and efficient bovine serum albumin (BSA) culture strategy. The results of in vitro experiments showed that CeO2@BSA had a significant ability to promote osteogenesis in hPDLCs at lower concentrations, which was mediated through TGF-β signaling pathway. However, this ability was diminished at high concentrations, which may be caused by excessive activation of autophagy. Notably, the osteogenic potential of hPDLCs was inhibited after autophagy was blocked. The construction of tissue-engineered membranes confirmed that CeO2@BSA facilitated reconstruction of periodontal bone defects in Sprague–Dawley (SD) rats. Our work demonstrated that CeO2@BSA exhibited efficient therapeutic effects in osteogenic differentiation and periodontal bone defect repair, while greatly expanding the application of CeO2@BSA in disease treatment.

The addition of zinc ions to polymer-ceramic composites accelerated osteogenic differentiation of human mesenchymal stromal cells

Critical-sized bone defects, caused by congenital disorders or trauma, are defects that will not heal spontaneously and require surgical intervention. Recent advances in biomaterial design for the treatment of such defects focus on improving their osteoinductive properties. Here, we propose a bioactive composite with high ceramic content composed of poly(ethyleneoxide terephthalate)/poly(butylene terephthalate) (1000PEOT70PBT30, PolyActive, PA) and 50 % beta-tricalcium phosphate (β-TCP) with the addition of zinc in a form of a coating on the TCP particles. Due to its essential role in bone homeostasis, we hypothesised that the addition of zinc to the polymer-ceramic composite will further enhance its osteogenic properties. β-TCP particles were immersed in a zinc solution with a concentration of 15 or 45 mM. The addition of zinc did not alter the β-TCP composition or the release of calcium or phosphate ions. 3D porous 1000PEOT70PBT30 - β-TCP scaffolds were additively manufactured by “3D fibre deposition” and their ability to support the osteogenic differentiation was assessed by culturing clinically relevant human mesenchymal stromal cells (hMSCs) on the scaffolds for 3, 7, 14 and 28 days. The expression of osteogenic gene markers was increased in the presence of both zinc concentrations. Remarkably, upregulation of osteocalcin (OCN), a late osteogenic marker, was observed after three days of culture. Furthermore, enhanced extracellular matrix (ECM) production and mineralization was observed. These findings support the existing evidence on the osteogenic properties of zinc and further demonstrate that the incorporation of zinc into a polymer-ceramic composite could be a promising strategy in the field of regeneration of critical-sized bone defects.

Impact of Different Preparations of Tooth Graft vs Xenogeneic Bone Graft on Bone Healing: An Experimental Study.

This study aims to compare the effect of demineralized xenogeneic tooth graft in its two forms, particulate and block, with bovine xenograft in the healing of a rabbit tibial bone defect model. Two monocortical bony defects were made in the right tibias of 36 rabbits, and were divided into four groups. Group I defects were left empty, while group II, III, and IV were filled with bovine xenograft, demineralized particulate tooth graft, and demineralized perforated block tooth graft, respectively for evaluation of the bone healing process. Three rabbits from each group were euthanized at 2, 4, and 6 weeks after surgery. The bone specimens were processed and stained with hematoxylin and eosin (H&E) and osteopontin (OPN) immunohistochemical staining. The results were subjected to image analysis and quantitative evaluation. Demineralized particulate tooth graft showed the best bone healing capacity compared to all other groups at all time points tested, as it showed a large amount of the formed bone, rapid closure of the defect with a significant increase in OPN expression, and the least amount of the residual grafted particles. In comparison to bovine xenograft and demineralized dentin block graft, the demineralized particulate tooth grafting material is a promising bone grafting substitute as it proved to be osteoconductive, biocompatible, and bioresorbable. Demineralized tooth grafting material can aid in the regeneration of large bone defects, leading to improvement in the filling of the bone defects which can help in oral and maxillofacial reconstruction.