Rabbit Femoral Defect Research Articles

Long-term biological performance of injectable and degradable calcium phosphate cement

Enhancing degradation of poorly degrading injectable calcium phosphate (CaP) cements (CPCs) can be achieved by adding poly(lactic-co-glycolic acid) (PLGA) microparticles, generating porosity after polymer degradation. CPC-PLGA has proven to be biodegradable, although its long-term biological performance is still unknown. Optimization of injectability could be achieved via addition of carboxymethyl cellulose (CMC). Here, we evaluated the long-term in vivo performance of CPC-PLGA with or without the lubricant CMC in comparison to the devitalized bovine bone mineral (DBBM) predicate device Bio-Oss®. Rabbit femoral bone defects were injected with a CPC-formulation or filled with Bio-Oss® granules. Samples were retrieved at 6 and 26 weeks. Material degradation for Bio-Oss® was marginal, starting with 57% material remnants at implantation, 49% at 6 weeks, and 35% at 26 weeks, respectively. In contrast, CPC-PLGA and CPC-PLGA-CMC showed significant material degradation, starting with 100% material remnants at implantation, 56 and 78% at 6 weeks, and 8 and 21% at 26 weeks. Bone formation showed to be rapid for Bio-Oss®, with 24% at 6 weeks, and a similar value (27%) at 26 weeks. Both CPC-PLGA and CPC-PLGA-CMC showed a continuous temporal increase in bone formation, with 13 and 6% at 6 weeks, and 44 and 32% at 26 weeks. This study showed that CPC-PLGA induces favorable bone responses with >90% degradation and >40% new bone formation after an implantation period of 26 weeks.

Improving the osteogenesis and degradability of biomimetic hybrid materials using a combination of bioglass and collagen I

As an inorganic bone graft, the traditional bioglass 45S5 can offer good bioactivity for osteogenesis. Type I collagen (Col-1) can mimic the organic components of natural bone in hybrid materials. Hence, in this study, biomimetic hybrid materials [CBGM (Collagen Bioactive Glass Morsels), CBGM1, CBGS (Collagen Bioactive Glass Strips) and CBGS1] were fabricated using 45S5 granules and high purity Col-1 at a proportion of 8.5:1.5. The surface features of these materials were observed using scanning electron microscopy and element energy dispersive spectroscopic (EDS). The activity of MC3T3-E1 cells, including adhesion, proliferation and gene expression, was significantly improved in the CBGS and CBGS1 groups compared with the 45S5 group. Additionally, X-ray, micro computed tomography, EDS and histomorphology showed that these hybrid materials had significantly enhanced osteogenesis and degradation 6 and 12weeks after implantation in rabbit femoral condylar defects compared with 45S5. CBGS and CBGS1 were significantly better than CBGM and CBGM1 in terms of osteogenesis and degradability. Consequently, with the improved osteogenesis and the faster degradation rate, the hybrid materials CBGS and CBGS1 are promising bone graft candidates for clinical application.

Influence of single and binary doping of strontium and lithium on in vivo biological properties of bioactive glass scaffolds

Effects of strontium and lithium ion doping on the biological properties of bioactive glass (BAG) porous scaffolds have been checked in vitro and in vivo. BAG scaffolds were prepared by conventional glass melting route and subsequently, scaffolds were produced by evaporation of fugitive pore formers. After thorough physico-chemical and in vitro cell characterization, scaffolds were used for pre-clinical study. Soft and hard tissue formation in a rabbit femoral defect model after 2 and 4 months, were assessed using different tools. Histological observations showed excellent osseous tissue formation in Sr and Li + Sr scaffolds and moderate bone regeneration in Li scaffolds. Fluorochrome labeling studies showed wide regions of new bone formation in Sr and Li + Sr doped samples as compared to Li doped samples. SEM revealed abundant collagenous network and minimal or no interfacial gap between bone and implant in Sr and Li + Sr doped samples compared to Li doped samples. Micro CT of Li + Sr samples showed highest degree of peripheral cancellous tissue formation on periphery and cortical tissues inside implanted samples and vascularity among four compositions. Our findings suggest that addition of Sr and/or Li alters physico-chemical properties of BAG and promotes early stage in vivo osseointegration and bone remodeling that may offer new insight in bone tissue engineering.

Pulsed electromagnetic fields promote osteogenesis and osseointegration of porous titanium implants in bone defect repair through a Wnt/β-catenin signaling-associated mechanism.

Treatment of osseous defects remains a formidable clinical challenge. Porous titanium alloys (pTi) have been emerging as ideal endosseous implants due to the excellent biocompatibility and structural properties, whereas inadequate osseointegration poses risks for unreliable long-term implant stability. Substantial evidence indicates that pulsed electromagnetic fields (PEMF), as a safe noninvasive method, inhibit osteopenia/osteoporosis experimentally and clinically. We herein investigated the efficiency and potential mechanisms of PEMF on osteogenesis and osseointegration of pTi in vitro and in vivo. We demonstrate that PEMF enhanced cellular attachment and proliferation, and induced well-organized cytoskeleton for in vitro osteoblasts seeded in pTi. PEMF promoted gene expressions in Runx2, OSX, COL-1 and Wnt/β-catenin signaling. PEMF-stimulated group exhibited higher Runx2, Wnt1, Lrp6 and β-catenin protein expressions. In vivo results via μCT and histomorphometry show that 6-week and 12-week PEMF promoted osteogenesis, bone ingrowth and bone formation rate of pTi in rabbit femoral bone defect. PEMF promoted femoral gene expressions of Runx2, BMP2, OCN and Wnt/β-catenin signaling. Together, we demonstrate that PEMF improve osteogenesis and osseointegration of pTi by promoting skeletal anabolic activities through a Wnt/β-catenin signaling-associated mechanism. PEMF might become a promising biophysical modality for enhancing the repair efficiency and quality of pTi in bone defect.

Experimental research about the copolymers of DR-PLGA microcapsule and CPC on the treatment of rabbit femoral defect model

Objective To study the effects about rhizoma drynariae poly(lactic-co-glycolic acid) (DR-PLGA) /Calcium phosphate cement (CPC) composite scaffold on treating rabbit femoral bone defect. Methods Eight Newzealand rabbits were randomly divided into experiment group(n=4) and control group (n=4). The preparation of rabbit femoral bone defect model, separately implanted DR-PLGA/CPC scaffold and PLGA/CPC scaffold. After 4, 8 weeks, we took out the materials, observed with X-ray, gross anatomy, histology observation to evaluate the osteogenetic activity, the effect of accelerating the healing of bone defect. Resuits At the 4th week and 8th week after implantation, the effect of promoting fracture healing and osteogenic activity of the experiment group were greater than those in the control group. Conclusions DR-PLGA combined with CPC could induce new bone formation, promote the healing of rabbit femoral defect. Key words: Polypodiacease; Rhizoma-drynariae/poly, lactic-co-glycolide facid; Calcium phosphate cement; Rabbits; Treatment outcome

Evaluation of a self-expandable mineral-collagen composite implant as an osteoconductive scaffold for bone growth and regeneration in a rabbit femoral bone defect model

Evaluation of a self-expandable mineral-collagen composite implant as an osteoconductive scaffold for bone growth and regeneration in a rabbit femoral bone defect model

Oxidatively Degradable Poly(thioketal urethane)/Ceramic Composite Bone Cements with Bone-Like Strength.

Synthetic bone cements are commonly used in orthopaedic procedures to aid in bone regeneration following trauma or disease. Polymeric cements like PMMA provide the mechanical strength necessary for orthopaedic applications, but they are not resorbable and do not integrate with host bone. Ceramic cements have a chemical composition similar to that of bone, but their brittle mechanical properties limit their use in weight-bearing applications. In this study, we designed oxidatively degradable, polymeric bone cements with mechanical properties suitable for bone tissue engineering applications. We synthesized a novel thioketal (TK) diol, which was crosslinked with a lysine triisocyanate (LTI) prepolymer to create hydrolytically stable poly(thioketal urethane)s (PTKUR) that degrade in the oxidative environment associated with bone defects. PTKUR films were hydrolytically stable for up to 6 months, but degraded rapidly (<1 week) under simulated oxidative conditions in vitro. When combined with ceramic micro- or nanoparticles, PTKUR cements exhibited working times comparable to calcium phosphate cements and strengths exceeding those of trabecular bone. PTKUR/ceramic composite cements supported appositional bone growth and integrated with host bone near the bone-cement interface at 6 and 12 weeks post-implantation in rabbit femoral condyle plug defects. Histological evidence of osteoclast-mediated resorption of the cements was observed at 6 and 12 weeks. These findings demonstrate that a PTKUR bone cement with bone-like strength can be selectively resorbed by cells involved in bone remodeling, and thus represent an important initial step toward the development of resorbable bone cements for weight-bearing applications.

Remodeling of an injectable, settable, and cell-degradable composite bone cement with bone-like strength in a rabbit femoral plug defect model

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Mechanical and in vivo assessment of injectable germanium based glass ionomer cements for vertebroplasty

Event Abstract Back to Event Mechanical and in vivo assessment of injectable germanium based glass ionomer cements for vertebroplasty Brett Dickey1, Lauren Kiri2, Caitlin Pierlot2 and Daniel Boyd1, 2 1 Dalhousie University, School of Biomedical Engineering, Canada 2 Dalhousie University, Department of Applied Oral Sciences, Canada Introduction: Vertebroplasty (VP) is a minimally invasive procedure where bone cement is injected into vertebral fractures for palliative relief via fracture stabilization. Basic requirements of VP cements include 5-20 min of injection time and lasting compression strength (σc) >30 MPa [1],[2]. Germanium containing glass ionomer cements (Ge-GICs) demonstrate appropriate handling characteristics for VP [3], but weaken significantly over time and little is known regarding their in vivo performance. The objectives of this study were to: (i) establish composition-property relationships to mitigate the known mechanical decline of Ge based GICs; (ii) quantify their potential as injectable cements; and (iii) conduct a pilot animal trial to gain preliminary biocompatibility data. Materials and Methods: Design of mixtures (DOM) was used to identify 12 glass compositions. Glasses were synthesized via a melt-quench technique, ground to ≤45 µm, and annealed (Tg – 30˚C). GICs were prepared by mixing glass powders with polyacrylic acid (Mw=12,700 g/mol, 50 wt% aq. sol.) at a 4:3 ratio. GIC σc was evaluated up to 180 days and DOM response models were produced for relevant time points. An additional composition (DG302) was interpolated from within the design space and synthesized to validate the DOM models. Injectability of DG302 GIC was assessed by profiling the force required to extrude cement from a 1 cc syringe with a 12 G cannula over time. AccelLAB (Boisbriand, CAN) was contracted for the in vivo pilot, where DG302 filled 4 subcritical femoral defects in 2 male NZ white rabbits with a sham control over an 8-week period (e.g. Fig. 1). Post-sacrifice, defects were scanned using MicroCT to reconstruct 3-D images of the implants, then sectioned, stained with Goldner’s Trichrome, and graded according to cell type and local host response. Systemic effects of the DG302 implants were also assessed via blood work. Results and Discussions: Ge-GIC mechanical performances were successfully improved, e.g. σc of DG302 increased from 51 MPa at 1 day to 71 MPa at 180 days. DOM models identified ZrO2/Na2O content as the most influential factor on σc, and SiO2:GeO2 ratio key to ensure long-term mechanical stability. DG302 injection profiles exhibited an initial injection force of 16 N that increased to 62 N after 15 min. All animals maintained healthy weights and appetites, and concerns regarding the long-term stability of Ge-GICs were further mitigated as DG302 implants remained intact over the 8 weeks studyA. Conclusion: Precise manipulation of glass chemistry yields Ge-GICs with clinically viable handling and mechanical properties that are stable in vivo. These characteristics exemplify a practical foundation to further the investigation of Ge-GICs for minimally invasive procedures such as VP. A. Full histopathological and hematological results to be obtained in October 2015 and not available at the time of abstract submission, but will be included in presentation of this work at WBC. Figure 1: MicroCT section of DG302 implant (identified by black arrow) in rabbit femoral defect model after 8 weeks.

Functionalized mesoporous bioactive glass scaffolds for enhanced bone tissue regeneration

Event Abstract Back to Event Functionalized mesoporous bioactive glass scaffolds for enhanced bone tissue regeneration Deliang Zeng1 and Xinquan Jiang1 1 The Ninth People’s Hospital affiliated to Shanghai Jiao Tong University, School of Mediceine, Department of Prosthodontics, China Introduction: Mesoporous bioactive glass (MBG), which possesses excellent bioactivity and biocompatibility, has played an important role in bone tissue regeneration. However, it is difficult to prepare MBG scaffolds with sufficient compressive strength for bone regeneration, which greatly hinder its development and applications. Materials and Methods: a simple powder processing technique has been successfully developed to fabricate a novel kind of MBG scaffolds (MBGS). The resultant MBGS not only possesses higher compressive strength up to 0.3 MPa and interconnected macro- structure with pore diameter of 100-300 μm, but also inherits the highly ordered mesoporous structure from MBG. Furthermore, amino or carboxylic groups could be successfully grafted (donated as N-MBGS and C-MBGS, respectively) through a post-grafting process. Results and Discussion: It is revealed that both MBGS and functionalized MBGSs could significantly promote the proliferation and osteogenic differentiation of bone marrow stromal cells (bMSCs) by improving their bone-related gene expression (runt-related transcription factor 2 (runx2), alkaline phosphatase (ALP), bone sialoprotein (BSP) and osteocalcin (OCN)). Due to the positively charged surface, N-MBGS presented the highest in vitro osteogenic capability among three samples. Moreover, the in vivo testing results in a rabbit femur defect model demonstrated that N-MBGS could result in more bone regeneration, in comparison with MBGS and C-MBGS. In addition to the surface characteristics, it is believed that the decreased degradation rate of N-MBGS plays a vital role in the bone regeneration. Conclusions: MBGS modified with amino groups not only provided suitable surface for cell to proliferate and differentiate, but also decreased the degradation rate to adapt new bone formation. And the novel surface characteristics of N-MBGS combined with bMSCs exhibited the largest newly formed bone area in the rabbit femur defects model. These indicate that the N-MBGS scaffold facilely fabricated by combining the powder processing technique has practical application potentials for bone regeneration. Figure 1: Effective scaffold system for enhanced bone regeneration. Figure 2: (A) Digital microscopic photograph, (B) Reverse color photograph, (C) SEM image and (D) SEM image in high magnification of MBGS, E) The compressive strength and porosity of MBGS and the contrast. (*MBG scaffolds prepared by the polyurethane foam template method) Figure 3: The color images represent sequential fluorescent labeling of AL, CA and the cross sections of rabbit femurs implanted (Histological observation of new bone formation in three kinds of scaffolds after 12 weeks). We thank Pro. Yongsheng Li and PhD. Xingdi Zhang for their involvement in the present study. And this work was financially supported by the 973 Program (Grant No. 2012CB933600); the National Natural Science Foundation of China (Grant Nos. 81300853)

Effect of low-level mechanical vibration on osteogenesis and osseointegration of porous titanium implants in the repair of long bone defects.

Emerging evidence substantiates the potential of porous titanium alloy (pTi) as an ideal bone-graft substitute because of its excellent biocompatibility and structural properties. However, it remains a major clinical concern for promoting high-efficiency and high-quality osseointegration of pTi, which is beneficial for securing long-term implant stability. Accumulating evidence demonstrates the capacity of low-amplitude whole-body vibration (WBV) in preventing osteopenia, whereas the effects and mechanisms of WBV on osteogenesis and osseointegration of pTi remain unclear. Our present study shows that WBV enhanced cellular attachment and proliferation, and induced well-organized cytoskeleton of primary osteoblasts in pTi. WBV upregulated osteogenesis-associated gene and protein expression in primary osteoblasts, including OCN, Runx2, Wnt3a, Lrp6 and β-catenin. In vivo findings demonstrate that 6-week and 12-week WBV stimulated osseointegration, bone ingrowth and bone formation rate of pTi in rabbit femoral bone defects via μCT, histological and histomorphometric analyses. WBV induced higher ALP, OCN, Runx2, BMP2, Wnt3a, Lrp6 and β-catenin, and lower Sost and RANKL/OPG gene expression in rabbit femora. Our findings demonstrate that WBV promotes osteogenesis and osseointegration of pTi via its anabolic effect and potential anti-catabolic activity, and imply the promising potential of WBV for enhancing the repair efficiency and quality of pTi in osseous defects.

IGF-loaded silicon and zinc doped brushite cement: physico-mechanical characterization and in vivo osteogenesis evaluation.

Dopants play critical roles in controlling the physical, mechanical, degradation kinetics, and in vivo properties of calcium phosphates. The aim of the present study was to evaluate the effects of silicon (Si) and zinc (Zn) dopants on the physico-mechanical and in vivo osteogenesis properties of brushite cements (BrCs) alone and in combination with insulin like growth factor 1 (IGF-1). Addition of 0.5 wt% Si did not alter the setting time, β-TCP content, and compressive strength of BrCs significantly; however, 0.25 wt% Zn incorporation was accompanied by a significant decrease in mechanical strength from 4.78 ± 0.21 MPa for pure BrC to 3.78 ± 0.59 MPa and 3.28 ± 0.22 MPa for Zn-BrC and Si/Zn-BrC, respectively. The in vivo bone regeneration properties of doped BrCs alone and in combination with IGF-1 were assessed and compared using chronological radiography, histology, scanning electron microscopy and fluorochrome labeling at 2 and 4 months post implantation in a rabbit femoral defect model. Based on in vivo characterization focusing on osteogenesis and vasculogenesis, Si-BrC and Si/Zn-BrC showed the best performance followed by Zn-BrC and pure BrCs. Addition of IGF-1 further improved bone regeneration. Our findings confirm that addition of Si and/or Zn alters the physico-mechanical properties of BrCs and promotes the early stage in vivo osseointegration and bone remodeling properties.

Relevance of fiber integrated gelatin-nanohydroxyapatite composite scaffold for bone tissue regeneration

Porous nanohydroxyapatite (nanoHA) is a promising bone substitute, but it is brittle, which limits its utility for load bearing applications. To address this issue, herein, biodegradable electrospun microfibrous sheets of poly(L-lactic acid)-(PLLA)–polyvinyl alcohol (PVA) were incorporated into a gelatin–nanoHA matrix which was investigated for its mechanical properties, the physical integration of the fibers with the matrix, cell infiltration, osteogenic differentiation and bone regeneration. The inclusion of sacrificial fibers like PVA along with PLLA and leaching resulted in improved cellular infiltration towards the center of the scaffold. Furthermore, the treatment of PLLA fibers with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide enhanced their hydrophilicity, ensuring firm anchorage between the fibers and the gelatin–HA matrix. The incorporation of PLLA microfibers within the gelatin–nanoHA matrix reduced the brittleness of the scaffolds, the effect being proportional to the number of layers of fibrous sheets in the matrix. The proliferation and osteogenic differentiation of human adipose-derived mesenchymal stem cells was augmented on the fibrous scaffolds in comparison to those scaffolds devoid of fibers. Finally, the scaffold could promote cell infiltration, together with bone regeneration, upon implantation in a rabbit femoral cortical defect within 4 weeks. The bone regeneration potential was significantly higher when compared to commercially available HA (Surgiwear™). Thus, this biomimetic, porous, 3D composite scaffold could be offered as a promising candidate for bone regeneration in orthopedics.

In vivo behaviors of Ca(OH)2 activated nano SiO2 (nCa/nSi = 3) cement in rabbit model

In vivo behaviors of Ca(OH)2 activated nano SiO2 (nCa/nSi=3, TCS) cement were investigated in the rabbit femoral defects using the poly(methyl methacrylate) (PMMA) as control. The deposited apatite and CaCO3 layers round TCS paste surfaces were completely used to construct the new bone tissue. TCS paste could stimulate the formation of new bone tissue in marrow tissue. The osteostimulation was mainly attributed to the proliferation and differentiation effects of Ca and Si ions released from TCS paste on the osteoprogenitor cells. However, Calcium–Silicate–Hydrate (C–S–H) gel in TCS paste was harder to degradate than Ca(OH)2. TCS paste kept the original shape during implantation, and could not provide the pores or spaces for further formation of bone tissue. Osteolytic defects induced by wear particles from TCS paste surface could not be completely avoided, because of the interfacial strain and the extensive micromotion between TCS paste surface and new bone tissue. Overall, our results indicated that Ca(OH)2 activated nano SiO2 cement was bioactivity and osteostimulation. The further improvements of Ca(OH)2 activated nano SiO2 cement should be done by achieving a balance between biological properties and mechanical performances.

Degradation and silicon excretion of the calcium silicate bioactive ceramics during bone regeneration using rabbit femur defect model.

The investigation of the bone regeneration ability, degradation and excretion of the grafts is critical for development and application of the newly developed biomaterials. Herein, the in vivo bone-regeneration, biodegradation and silicon (Si) excretion of the new type calcium silicate (CaSiO3, CS) bioactive ceramics were investigated using rabbit femur defect model, and the results were compared with the traditional β-tricalcium phosphate [β-Ca3(PO4)2, β-TCP] bioceramics. After implantation of the scaffolds in rabbit femur defects for 4, 8 and 12weeks, the bone regenerative capacity and degradation were evaluated by histomorphometric analysis. While urine and some organs such as kidney, liver, lung and spleen were resected for chemical analysis to determine the excretion of the ionic products from CS implants. The histomorphometric analysis showed that the bioresorption rate of CS was similar to that of β-TCP in femur defect model, while the CS grafts could significantly stimulate bone formation capacity as compared with β-TCP bioceramics (P<0.05). The chemical analysis results showed that Si concentration in urinary of the CS group was apparently higher than that in control group of β-TCP. However, no significant increase of the Si excretion was found in the organs including kidney, which suggests that the resorbed Si element is harmlessly excreted in soluble form via the urine. The present studies show that the CS ceramics can be used as safe, bioactive and biodegradable materials for hard tissue repair and tissue engineering applications.

IN VIVOEVALUATION OF A NEW β-TRICALCIUM PHOSPHATE BONE SUBSTITUTE IN A RABBIT FEMUR DEFECT MODEL

Calcium phosphate ceramics, of a similar composition to that of mineral bone, and which possess the properties of bioactivity and osteoconductivity, have been widely used as substitutes for bone graft in orthopedic, plastic and craniofacial surgeries. A synthetic β-tricalcium phosphate, Osteocera™, a recently developed bone graft substitute, has been used in this study. To evaluate the affinity and efficacy of Osteocera™ as bone defect implant, we used a New Zealand white rabbit femur defect model to test the osteoconductivity of this new bone substitute. Alternative commercially available bone substitutes, Triosite®and ProOsteon500, were used as the control materials. These three bone substitutes show good biocompatibility, and no abnormal inflammation either infection was seen at the implantation sites. In the histological and histomorphometric images, newly formed bone grew into the peripheral pores in the bone substitutes. After six months implantation, the volume of bone formation was found to be 20.5 ± 5.2%, 29.8 ± 6.5% and 75.5 ± 4.9% of the potential total cavity offered by ProOsteon500, Triosite®and Osteocera™, respectively. The newly formed bone area within the femur defect section for Osteocera™ was significantly larger than ProOsteon500 and Triosite®. We concluded that Osteocera™ shows better bioresorbability, biocompatibility and osteoconductivity in the rabbit femur defect model.

Improving the osteointegration of Ti6Al4V by zeolite MFI coating

Osteointegration is crucial for success in orthopedic implantation. In recent decades, there have been numerous studies aiming to modify titanium alloys, which are the most widely used materials in orthopedics. Zeolites are solid aluminosilicates whose application in the biomedical field has recently been explored. To this end, MFI zeolites have been developed as titanium alloy coatings and tested in vitro. Nevertheless, the effect of the MFI coating of biomaterials in vivo has not yet been addressed. The aim of the present work is to evaluate the effects of MFI-coated Ti6Al4V implants in vitro and in vivo. After surface modification, the surface was investigated using field emission scanning electron microscopy (FE-SEM) and energy dispersive spectroscopy (EDS). No difference was observed regarding the proliferation of MC3T3-E1 cells on the Ti6Al4V (Ti) and MFI-coated Ti6Al4V (M−Ti) (p > 0.05). However, the attachment of MC3T3-E1 cells was found to be better in the M−Ti group. Additionally, ALP staining and activity assays and quantitative real-time RT-PCR indicated that MC3T3-E1 cells grown on the M−Ti displayed high levels of osteogenic differentiation markers. Moreover, Van-Gieson staining of histological sections demonstrated that the MFI coating on Ti6Al4V scaffolds significantly enhanced osteointegration and promoted bone regeneration after implantation in rabbit femoral condylar defects at 4 and 12 weeks. Therefore, this study provides a method for modifying Ti6Al4V to achieve improved osteointegration and osteogenesis.

Improving osteointegration and osteogenesis of three-dimensional porous Ti6Al4V scaffolds by polydopamine-assisted biomimetic hydroxyapatite coating.

Titanium alloys with various porous structures can be fabricated by advanced additive manufacturing techniques, which are attractive for use as scaffolds for bone defect repair. However, modification of the scaffold surfaces, particularly inner surfaces, is critical to improve the osteointegration of these scaffolds. In this study, a biomimetic approach was employed to construct polydopamine-assisted hydroxyapatite coating (HA/pDA) onto porous Ti6Al4V scaffolds fabricated by the electron beam melting method. The surface modification was characterized with the field emission scanning electron microscopy, energy dispersive spectroscopy, water contact angle measurement, and confocal laser scanning microscopy. Attachment and proliferation of MC3T3-E1 cells on the scaffold surface were significantly enhanced by the HA/pDA coating compared to the unmodified surfaces. Additionally, MC3T3-E1 cells grown on the HA/pDA-coated Ti6Al4V scaffolds displayed significantly higher expression of runt-related transcription factor-2, alkaline phosphatase, osteocalcin, osteopontin, and collagen type-1 compared with bare Ti6Al4V scaffolds after culture for 14 days. Moreover, microcomputed tomography analysis and Van-Gieson staining of histological sections showed that HA/pDA coating on surfaces of porous Ti6Al4V scaffolds enhanced osteointegration and significantly promoted bone regeneration after implantation in rabbit femoral condylar defects for 4 and 12 weeks. Therefore, this study provides an alternative to biofunctionalized porous Ti6Al4V scaffolds with improved osteointegration and osteogenesis functions for orthopedic applications.

Effects of particle size and porosity on in vivo remodeling of settable allograft bone/polymer composites.

Established clinical approaches to treat bone voids include the implantation of autograft or allograft bone, ceramics, and other bone void fillers (BVFs). Composites prepared from lysine-derived polyurethanes and allograft bone can be injected as a reactive liquid and set to yield BVFs with mechanical strength comparable to trabecular bone. In this study, we investigated the effects of porosity, allograft particle size, and matrix mineralization on remodeling of injectable and settable allograft/polymer composites in a rabbit femoral condyle plug defect model. Both low viscosity and high viscosity grafts incorporating small (<105 μm) particles only partially healed at 12 weeks, and the addition of 10% demineralized bone matrix did not enhance healing. In contrast, composite grafts with large (105-500 μm) allograft particles healed at 12 weeks postimplantation, as evidenced by radial μCT and histomorphometric analysis. This study highlights particle size and surface connectivity as influential parameters regulating the remodeling of composite bone scaffolds.

Doped tricalcium phosphate scaffolds by thermal decomposition of naphthalene: Mechanical properties and in vivo osteogenesis in a rabbit femur model.

Tricalcium phosphate (TCP) is a bioceramic that is widely used in orthopedic and dental applications. TCP structures show excellent biocompatibility as well as biodegradability. In this study, porous β-TCP scaffolds were prepared by thermal decomposition of naphthalene. Scaffolds with 57.64% ± 3.54% density and a maximum pore size around 100 μm were fabricated via removing 30% naphthalene at 1150°C. The compressive strength for these scaffolds was 32.85 ± 1.41 MPa. Furthermore, by mixing 1 wt % SrO and 0.5 wt % SiO2 , pore interconnectivity improved, but the compressive strength decreased to 22.40 ± 2.70 MPa. However, after addition of polycaprolactone coating layers, the compressive strength of doped scaffolds increased to 29.57 ± 3.77 MPa. Porous scaffolds were implanted in rabbit femur defects to evaluate their biological property. The addition of dopants triggered osteoinduction by enhancing osteoid formation, osteocalcin expression, and bone regeneration, especially at the interface of the scaffold and host bone. This study showed processing flexibility to make interconnected porous scaffolds with different pore size and volume fraction porosity, while maintaining high compressive mechanical strength and excellent bioactivity. Results show that SrO/SiO2 -doped porous TCP scaffolds have excellent potential to be used in bone tissue engineering applications.