Successful Bone Regeneration Research Articles

The Use of Cytoplast Titanium Reinforced Membrane for Horizontal Guided Bone Regeneration Case Report

uccessful implant osseointegration is dependent primarily upon adequate bone quantity and quality at the desired implant site. But often times the implant candidate, after proper clinical examination and evaluation of the patient's diagnostic information, lacks adequate bone quantity or volume for implant placement. Often times, the patient's has adequate height of bone but lacks bone width. The ability to predictably generate horizontal bone or bone width in preparation for dental implants, or guided bone regeneration (GBR) is an important and necessary procedure, in implant site preparation. Successful bone regeneration depends upon several factors. The first of which is to prevent soft tissue in growth into the bone graft material.

In vitro and in vivo evaluation of novel Tadalafil/β-TCP/Collagen scaffold for bone regeneration: A rabbit critical-size calvarial defect study

Different composite materials have been investigated in bone regeneration but none of them have a significant regeneration in a short time. In this study, the novel scaffold with the osteoinductive characteristic in order to accelerate bone regeneration for 6 weeks. Tadalafil/β-TCP/Collagen (TβC) and β-TCP/Collagen (βC) composite scaffolds were prepared and analyzed by porosity, biodegradability and MTT tests. And then, three bone defects (8mm diameter, n=6 group) were produced and filled with TβC, βC scaffolds and the third defect was unfilled as a control. Samples were taken and evaluated by histological, radiological and histomorphometric evaluation at 4 and 6 weeks. In vitro tests showed that both scaffold approximately had the same results in the percentage of porosity and in vitro cytotoxicity. Biodegradability of the βC scaffold was more than TβC scaffold. In vivo test showed bone regeneration was more in TβC scaffold at 6 weeks based on radiological and histopathologic analysis compared with βC scaffold and control groups. Histomorphometric analysis showed that the amount of the bone regeneration was significant in TβC group in comparison βC and control groups (P<0.05) at 6 weeks. This study highlights the promising application of TβC scaffold with Tadalafil for successful bone regeneration by enhancing osteogenesis.

Comparative Study between Laser Light Stereo-Lithography 3D-Printed and Traditionally Sintered Biphasic Calcium Phosphate Scaffolds by an Integrated Morphological, Morphometric and Mechanical Analysis.

In dental districts, successful bone regeneration using biphasic calcium phosphate materials was recently explored. The present study aimed to perform a comparative study between 3D-printed scaffolds produced by laser light stereo-lithography (SLA) and traditionally sintered biphasic calcium phosphate scaffolds by an integrated morphological, morphometric and mechanical analysis. Methods: Biphasic calcium phosphate (30% HA/70% β-TCP) samples, produced by SLA-3D-printing or by traditional sintering methods, were tested. The experimental sequence included: (1) Microtomography (microCT) analyses, to serve as control-references for the 3D morphometric analysis; (2) loading tests in continuous mode, with compression up to fracture, to reconstruct their mechanical characteristics; and (3) microCT of the same samples after the loading tests, for the prediction of the morphometric changes induced by compressive loading of the selected materials. All the biomaterials were also studied by complementary scanning electron microscopy to evaluate fracture regions and surfaces. Results: The characterization of the 3D mineralized microarchitecture showed that the SLA-3D-printed biomaterials offer performances comparable to and in some cases better than the traditionally sintered ones, with higher mean thickness of struts and pores. Interestingly, the SLA-3D-printed samples had a higher ultimate strength than the sintered ones, with a smaller plastic region. Moreover, by SEM observation, it was observed that fractures in the SLA-3D-printed samples were localized in the structure nodes or on the external shells of the rods, while all the traditionally sintered samples revealed a ductile fracture surface. Conclusions: The reduction of the region of plastic deformation in the SLA-3D-printed samples with respect to traditionally sintered biomaterials is expected to positively influence, in vivo, the cell adhesion. Both microCT and SEM imaging revealed that the studied biomaterials exhibit a structure more similar to human jaw than the sintered biomaterials.

Multifunctional mesoporous magnetic Mg2SiO4–CuFe2O4 core-shell nanocomposite for simultaneous bone cancer therapy and regeneration

Abstract Traditional bone grafts have shown their abilities for successful bone regeneration, but they are not able to address other critical problems such as infection and bone cancer beside bone regeneration. Multifunctional nanocomposites are highly being assessed as potential materials capable of addressing the mentioned crucial problems and basic requirements of bone regeneration simultaneously. In this study, by adopting a two-step strategy including sol-gel combustion and surfactant-assisted sol-gel methods, multifunctional Mg2SiO4–CuFe2O4 nanocomposite is synthesized. The nanocomposite's phase, morphology, textural properties, and elemental distribution are characterized and the results evidence that the mesoporous magnetic nanocomposite with core-shell structure is successfully obtained and no undesirable phase except Mg2SiO4 and CuFe2O4 is detected. Next, the bioactivity potential into simulated body fluid (SBF), antibacterial activity against both gram-positive and gram-negative bacteria, heat generation capability (hyperthermia), MTT assay, and cell attachment of the nanocomposite are assessed in vitro. After 21 days of soaking into SBF, the surface of nanocomposite is completely covered with Ca–P particles proving its bioactive nature. The nanocomposite has better antibacterial activity against E. coli rather than S. aureus bacteria. By exposing the nanocomposite to different external magnetic fields and constant frequency, it is found that based on the need the heat generation capability can be altered. The cell viability increases with diluting the concentration of nanocomposite from 100 to 25 mg/mL and cell attachment study shows that MG63 cells are spread and attached to the surface of nanocomposite. Through the results of present study, it can be suggested that the nanocomposite by showing antibacterial activity which prevents localized infection and also heat generation capability which eradicates bone cancerous cells is regarded promising for simultaneous bone cancer therapy and regeneration.

Controlled release of BMP-2 from titanium with electrodeposition modification enhancing critical size bone formation.

In this study, a porous Ti-alloy based implant with an interconnected channel structure (MAO-CaP-BMP2) is fabricated using a method combining 3D printing, microarc oxidation (MAO) treatment, and co-precipitation of Ca,P layer with BMP-2 technique. The macroporous structure with pore size of 600 μm made by 3D printing not only enhances the ingrowth of cells but also allows the formation of blood vessels inside the implant. As a result, the new bond formation is promoted. In addition, the microporous dioxide layer formed on the implant surface by MAO provides the sites for co-precipitation of Ca,P layer with BMP-2. The microstructure allows the prolonged release of BMP-2. Our results show that a sustained release of BMP-2 over 35 days is achieved for MAO-CaP-BMP2 group longer than Ti without MAO modification group and without Ca,P electrochemical deposition group. The slow release of BMP-2 at the bone/implant interface for a long period of time leads to enhancement of the osseointegration between the implant and surrounding bones. This result indicates that MAO-CaP-BMP2 is a good candidate of growth factor carrier. Successful regeneration of bone requires the concomitant processes of osteogenesis and neovascularization. MAO-CaP-BMP2 modified Ti-alloy implant is both osteoinductive and osteoconductive which can create better osteogenesis and angiogenesis. As a result, it can enhance bone formation.

Investigation of Integrated Effects of Hydroxyapatite and VEGF on Capillary Morphogenesis of Endothelial Cells.

Major drawbacks of using autografts and allografts for repairing large bone defects/injuries are the shortage of available tissues and potential disease transmission. Bone tissue engineering is believed to be a promising alternative to bone grafts. The concomitant formation of vascular networks within the tissue engineered constructs for successful bone regeneration still remains a challenge. The physicochemical properties of a tissue microenvironment are known to regulate vascular network formation. However, our understanding of the mechanism, by which endothelial cells integrate these physicochemical signals emanating from the microenvironment to undergo capillary morphogenesis, is limited. In this study, the integrated effects of the vascular endothelial growth factor (VEGF), pro-angiogenic molecule, and hydroxyapatite (HA), widely used as an additive and a scaffold in bone reconstructive surgery, on capillary formation of human umbilical vein endothelial cells (HUVECs) were investigated. Toward this, HUVECs were seeded on scaffolds composed of 15% (w/v) poly(ethylene glycol) diacrylate, 5% (w/v) gelatin methacrylate (GelMA), and 1% (w/v) photoinitiator. The concentration of HA was varied from 0% to 0.2% (w/v). The study demonstrated that HA elicited an inhibitory response. The presence of VEGF promoted a sprouting response with a significant enhancement in the number of sprouts observed in the case of gels with higher concentrations of HA.

Design of a Randomized Controlled Clinical Study of tissue-engineered osteogenic materials using bone marrow-derived mesenchymal cells for Maxillomandibular bone defects in Japan: the TEOM study protocol

BackgroundMaxillomandibular bone defects arise from maxillofacial injury or tumor/cyst removal. While the standard therapy for bone regeneration is transplantation with autologous bone or artificial bone, these therapies are still unsatisfactory. Autologous bone harvesting is invasive and occasionally absorbed at the implanted site. The artificial bone takes a long time to ossify and it often gets infected. Therefore, we have focused on regenerative therapy consisting of autologous bone marrow-derived mesenchymal cells (BM-MSCs), which decreases the burden on patients. Based on our previous research in patients with maxillomandibular bone defects or alveolar bone atrophy using a mixture of BM-MSCs, platelet-rich plasma (PRP), thrombin, and calcium, we confirmed the efficacy and acceptable safety profile of this treatment. In this investigator-initiated clinical study (the TEOM study), we intended to add β-tricalcium phosphate (β-TCP) owing to large defect with patients. The TEOM study aimed to evaluate the efficacy and safety of bone regeneration using mixtures of BM-MSCs in patients with bone defects resulting from maxillofacial injury, and tumor/cyst removal in the maxillomandibular region.MethodsThe TEOM study is an open-label, single-center, randomized controlled study involving a total of 83 segments by the Fédération Dentaire Internationale numbering system in maxillomandibular bone defects that comprise over 1/3 of the maxillomandibular area with a remaining bone height of ≤10 mm. The primary endpoint is rate of procedure sites with successful bone regeneration defined as a computed tomography (CT) value of more than 400 and a bone height of more than 10 mm. Our specific hypothesis is that the number of required regions was calculated assuming that the rate of procedure sites with successful bone regeneration is similar and the non-inferiority margin is 15.0%.DiscussionThe TEOM study is the first randomized controlled study of regenerative treatment using BM-MSCs for large maxillomandibular bone defects. We will evaluate the efficacy and safety in this study to provide an exploratory basis for the necessity of BM-MSCs for these patients.Trial registrationThis trial was registered at the University Hospital Medical information Network Clinical Trials Registry (UMIN-CTR Unique ID: UMIN000020398; Registration Date: Jan 15, 2016; URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000016543).

Role of Synthetic Hydroxyapatite—In Socket Preservation: A Systematic Review and Meta-analysis

The literature search was performed for the studies published in the English language independently by all four authors (search team) in the Medline database through the PubMed search engine for the past 5 years. The study involved predetermined inclusion and exclusion criteria for the search. The final lists of clinical trials were analyzed to determine the existing evidence and suggested the mechanism of action. The search resulted in 117 titles. After application of inclusion and exclusion criteria, a total of seven studies were found eligible for this systematic review. Out of seven, two studies were found eligible for meta-analysis whereas remaining included for the systematic review. The meta-analysis favors socket grafting compared to control in terms of preservation of existing bone height and width. The SHA grafting showed successful bone regeneration with less connective tissue component. The histomorphometric evaluation showed a good bone regeneration associated with SHA than xenograft. Within the limitations of this meta-analysis, the synthetic GSM can be used for socket grafting. In the wake of increasing graft materials in the market and different origin raw material sources for the preparation of graft materials, clinicians are in dilemma for selection and its use. The success of grafting depends on the selection of appropriate material with a suitable calcium/phosphate (Ca/P) ratio. The review provided available evidence for the use of SHA.

AP2a enhanced the osteogenic differentiation of mesenchymal stem cells by inhibiting the formation of YAP/RUNX2 complex and BARX1 transcription.

ObjectivesBone regeneration by bone tissue engineering is a therapeutic option for bone defects. Improving the osteogenic differentiation of mesenchymal stem cells (MSCs) is essential for successful bone regeneration. We previously showed that AP2a enhances the osteogenic differentiation in MSCs. The present study investigated the mechanism of how AP2a regulates the direct differentiation.Materials and methodsCo‐immunoprecipitation and ChIP assays were carried out to investigate the underlying mechanism in MSCs differentiation. The osteogenic differentiation potential was determined by mineralization ability and the expression of osteogenic marker in vitro and the in vivo bone‐like tissue generation in nude mice.ResultsWe show that AP2a can compete with RUNX2, a key transcription factor in osteogenic differentiation, to recruit YAP and release the inhibition of RUNX2 activity from YAP by forming YAP‐AP2a protein complex. YAP‐AP2a protein complex also interacts with the BARX1 promoter through AP2a, inhibit the transcription of BARX1. Moreover, BARX1 inhibits osteogenic differentiation of MSCs.ConclusionsOur discoveries revealed that AP2a may regulate the osteogenic differentiation in an indirect way through competing with RUNX2 to relieve the RUNX2 activity which inhibited by YAP, and also in a direct way via targeting the BARX1 and directly repressed its transcription. Thus, our discoveries shed new light on the mechanism of direct differentiation of MSCs and provide candidate targets for improving the osteogenic differentiation and enhancing bone tissue regeneration.

Dosage and composition of bioactive glasses differentially regulate angiogenic and osteogenic response of human MSCs.

Vascularization of the fracture site and cell-mediated deposition of the mineralized matrix are crucial determinants for successful bone regeneration after injury. Ceramic biomaterials such as bioactive glasses (BAGs) that release bioactive ions have shown promising results in bone defect regeneration. However, it remains unclear how the dosage and composition of bioactive ions influence the angiogenic and osteogenic behavior of primary human mesenchymal stromal cells (MSCs). Here, we show that exposure to ionic dissolution products from 1393 and 45S5 BAGs can evoke distinct angiogenic and osteogenic responses from primary MSCs in a dose- and composition-dependent manner. Significantly higher concentrations of the pro-angiogenic factors VEGF, HGF, PIGF, angiopoietin, and angiogenin were detected in conditioned media (CM) from MSCs exposed to 45S5, but not 1393, BAGs. Application of this CM to human umbilical vein endothelial cells (HUVECs) resulted in robust 2D tube formation in vitro. Osteogenic differentiation of MSCs was assessed by gene expression analysis and mineralization assays. Low concentrations (0.1% w/v) of 1393 BAGs significantly enhanced the gene expression of RUNX2 and ALP and induced an earlier onset of matrix mineralization compared to all other groups. We further tested whether simultaneous exposure to both BAGs would improve both angiogenic secretion and osteogenic differentiation of MSCs, and did not find evidence to support this hypothesis. Our results provide evidence of BAG composition-dependent enhancement of primary human MSCs' regenerative function, besides also underlining the importance of an in vitro evaluation of the dose-response relationship to translate BAG based approaches into safe and effective clinical therapies. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 2827-2837, 2018., 2018.

Fabrication of Hydroxyapatite/Cellulose Fiber Composite with Sheet-Like Structure

Natural bone is a complex material with well-designed architecture. To achieve successful bone integration and regeneration, the constituent and structure of bone-repairing scaffolds need to be flexible and biocompatible. HAp, as the main composition of bone minerals, has excellent biocompatibility, while CMC comprised of a three-dimensional network were high flexibility. Therefore, CMC/HAp composite have been attracted attention due to the development of bone tissue engineering. In this work, carboxymethyl cellulose (CMC)/hydroxyapatite (Ca10(PO4)6(OH)2; HAp) composite have been developed as three-dimensional scaffold for bone tissue engineering. Scanning electron microscopy revealed that the CMC/HAp composite have sheet-like structure. The amount of precipitated HAp of CMC/HAp composite was investigated using Thermogravimetric analysis. The amount of precipitated HAp in products prepared with 100 mg CMC was 49.8 wt%, while the amount of precipitated HAp in products prepared with 1000 mg CMC was 22.3 wt%. These results revealed that the amount of precipitated HAp in CMC/HAp composite was affected by CMC amount as prepared.

Fabrication and characterization of collagen-hydroxyapatite-based composite scaffolds containing doxycycline via freeze-casting method for bone tissue engineering.

In this study, hydroxyapatite nanoparticles containing 10% doxycycline, a structural isomer of tetracycline, was prepared by the co-precipitation method. It was added to collagen solution for the preparation of the scaffold with freeze-casting method in order to develop a composite scaffold with both antibacterial and osteoinductive properties for repairing bone defects. The scaffolds were evaluated regarding their morphology, porosity, degradation and cellular response. The scaffolds for further investigation were added in a rat calvaria defect model. The study showed that after eight weeks, the bone formation was relatively higher in the collagen/nano-hydroxyapatite/doxycycline group with completely filled defect when compared with other groups. Histopathological evaluation showed that the defect in the collagen/nano-hydroxyapatite/doxycycline group was fully replaced by the new bone and connective tissue. Our results provide evidence supporting the possible applicability of doxycycline-containing scaffolds for successful bone regeneration.

Acellular Dermal Matrix as a Barrier for Guided Bone Regeneration of Dehiscence Defects Around Dental Implants

The presence of hard tissue dehiscence and thin periodontal biotype in the esthetic area is a challenge that can jeopardize function and aesthetic outcome of implants. Here, we present a successful simultaneous soft tissue and bone regeneration of dehiscence defects in the maxillary incisor region. The novelty of this case lies in the simultaneous bone regeneration and soft tissue augmentation and the use of acellular dermal matrix as a barrier for regeneration and biotype conversion around dental implants. Reentry surgery 5 months after soft tissue and bone augmentation showed more than 95% new bone formation at the facial surface of implants and histological evidence of new vital bone formation. Biotype conversion from thin (<0.8 mm) to thick (2 mm) was noted in the area.

Evaluation of matrix metalloproteases as early biomarkers for bone regeneration during the applied Masquelet therapy for non-unions

IntroductionIn the current study, we sought to determine if serum concentrations of MMPs correlate with bone regeneration occurring during the course of the Masquelet-therapy and to identify if MMPs may serve as early biomarkers reflecting successful bone regeneration and tissue remodeling. Material and methodsThis study was designed as a prospective clinical observer study. We compared serum samples over the time of treatment, as a matched-pair analysis, from 10 patients who were treated successfully with the Masquelet-therapy (Responder) with 10 patients who did not respond to the Masquelet-therapy (Non-Responder). The quantitative measurement was performed with Luminex Performance Human High Sensitivity Assays according to manufacturer’s instructions. The lab technician performing the Luminex assays was blinded to both patient data and clinical outcome. ResultsAnalysis of the expression pattern of MMP-2, -8 and -9 showed significant differences between groups. Two days after the first step of the Masquelet therapy Responder showed peak values of MMP-8 and MMP-9 that where significantly higher (p = 0.003 and p = 0.042, respectively) than in Non-Responder. In contrast serum levels of MMP-2 were lower after the first step of the Masquelet therapy in the Non-Responder group. The ratio of MMP-9 and MMP-2 was significantly higher in the Responder group two days after step I (p = 0.031) as well as 4 weeks after step II (p = 0.030). ConclusionThe findings of the current study emphasize the potential role of MMPs as biomarkers in bone remodeling. In particular, a distinct expression of MMP-2 correlates with successful bone regeneration, whereas initial overexpression of MMP-2 serum levels might identify patients that have a higher risk for a poor outcome of the Masquelet-therapy. Furthermore, we were able to introduce the serum analysis of the ratio of MMP-9 and MMP-2 as promising novel modality for early prediction of the outcome of the Masquelet therapy. Further analysis of this ratio over time subsequent to the second step might serve as an early indicator of a favorable response to the induced membrane technique.

In vitro evaluation of a biomaterial-based anticancer drug delivery system as an alternative to conventional post-surgery bone cancer treatment

Patients diagnosed with osteosarcoma are currently treated with intravenous injections of anticancer agents after tumor resection. However, due to remaining neoplastic cells at the site of tumor removal, cancer recurrence often occurs. Successful bone regeneration combined with the control of residual cancer cells presents a challenge for tissue engineering. Cyclodextrins loaded with chemotherapeutic drugs reversibly release the drugs over time. Hydroxyapatite bone biomaterials coated with doxorubicin-loaded cyclodextrin should release the drug with time after implantation directly at the original tumor site and may be a way to eliminate residual neoplastic cells. In the present study, we have carried out in vitro studies to evaluate such a drug-delivery system and have shown that doxorubicin released from cyclodextrin-coated hydroxyapatite retained biological activity and exhibited longer and higher cytotoxic effects on both cancer (osteosarcoma cells) and healthy cells (primary osteoblasts and endothelial cells) compared to biomaterials without cyclodextrin loaded with doxorubicin. Furthermore, doxorubicin released from biomaterials with cyclodextrin moderately induced the expression of tumor suppressor protein p53 whereas p21 expression was similar to control cells. In addition, hypoxic conditions, which occur after implantation until blood-flow to the area is regenerated, protected endothelial cells and primary osteoblasts from doxorubicin-induced cytotoxicity. This chemo-protective effect was far less prominent for the osteosarcoma cells. These findings indicate that a hydroxyapatite-cyclodextrin-doxorubicin chemotherapeutic strategy may enhance the drug-targeting effect on tumor cells while protecting the more sensitive healthy cells for a period of time after implantation. A successful integration of such a drug delivery system might allow healthy cells to initially survive during the doxorubicin exposure period, while eliminating residual neoplastic cells.

Influence of Menopause on Inflammatory Cytokines during Murine and Human Bone Fracture Healing.

Postmenopausal females display a chronic inflammatory phenotype with higher levels of circulating pro-inflammatory cytokines. Furthermore, the inflammatory response to injury may be altered under estrogen-deficiency, because it was shown previously that estrogen-deficient mice displayed increased levels of the inflammatory cytokines Midkine (Mdk) and Interleukin-6 (IL-6) in the early fracture hematoma. Because a balanced immune response to fracture is required for successful bone regeneration, this might contribute to the delayed fracture healing frequently observed in osteoporotic, postmenopausal fracture patients. In this study, we aimed to investigate whether further cytokines in addition to Mdk and IL-6 might be affected by estrogen-deficiency after fracture in mice and whether these cytokines are also relevant during human fracture healing. Additionally, we aimed to investigate whether serum from male vs. female fracture patients affects osteogenic differentiation of human mesenchymal stem cells (MSCs). To address these questions, female mice were either sham-operated or ovariectomized (OVX) and subjected to standardized femur osteotomy. A broad panel of pro- and anti-inflammatory cytokines was determined systemically and locally in the fracture hematoma. In a translational approach, serum was collected from healthy controls and patients with an isolated fracture. Mdk and IL-6 serum levels were determined at day 0, day 14 and day 42 after fracture. Subgroup analysis was performed to investigate differences between male and female fracture patients after menopause. In an in vitro approach, human MSCs were cultured with the collected patient serum and osteogenic differentiation was assessed by qPCR and alkaline-phosphatase staining. Our results suggest an important role for the pro-inflammatory cytokines Mdk and IL-6 in the response to fracture in estrogen-deficient mice among all of the measured inflammatory mediators. Notably, both cytokines were also significantly increased in the serum of patients after fracture. However, only Mdk serum levels differed significantly between male and female fracture patients after menopause. MSCs cultivated with serum from female fracture patients displayed significantly reduced osteogenic differentiation, which was attenuated by Mdk-antibody treatment. In conclusion, our study demonstrated increased Mdk levels after fracture in OVX mice and female fracture patients after menopause. Because Mdk is a negative regulator of bone formation, this might contribute to impaired osteoporotic fracture healing.

In vitro and in vivo investigation of PLA/PCL scaffold coated with metformin-loaded gelatin nanocarriers in regeneration of critical-sized bone defects

Large bone defects constitute a major challenge in bone tissue engineering and usually fail to heal due to the incomplete differentiation of recruited mesenchymal stem cells (MSCs) into osteogenic precursor cells. As previously proposed, metformin (MET) induces differentiation of MSCs into osteoblastic lineages in vitro. We fabricated a Poly (lactic acid) and Polycaprolactone (PLA/PCL) scaffold to deliver metformin loaded gelatin nanocarriers (MET/GNs) to critical-sized calvarial bone defects in a rat model. The scaffolds were evaluated regarding their morphology, porosity, contact angle, degradation rate, blood compatibility, biomechanical, cell viability and their osteogenic differentiation. In animal study, the defects were filled with autograft, scaffolds and a group was left empty. qRT-PCR analyses showed the expression level of osteogenic and angiogenic markers considerably increased in MET/GNs-PLA/PCL. The in vivo results showed that MET/GNs-PLA/PCL improved bone ingrowth, angiogenesis and defect reconstruction. Our results represent the applicability of MET/GNs-PLA/PCL for successful bone regeneration.

Contrast-Enhanced Ultrasound Quantifies the Perfusion Within Tibial Non-Unions and Predicts the Outcome of Revision Surgery

Vascularity is one of the factors determining successful bone regeneration. This prospective study focused on quantifying the microperfusion of tibial non-unions with contrast-enhanced ultrasound (CEUS) 12 wk after revision surgery and comparing it with the osseous consolidation at a maximum of 24 mo assessed with standard radiography and computed tomography. Of 36 patients with tibial non-unions, 28 (77.8%) manifested consolidation, and 8 patients required further revision surgery. CEUS revealed significantly higher perfusion in consolidated versus persistent non-unions for all quantification parameters (e.g., wash-in perfusion index p = 0.036). Receiver operating characteristic analysis revealed a sensitivity of 82.1% and specificity of 75.0% with a wash-in perfusion index cutoff at 19.9 a.u. for diagnosing persisting non-unions. More than 1 y ahead of the final radiologic diagnostic examination, CEUS could predict eventual consolidation based on the osseous perfusion as soon as 12 wk postoperatively. This information can be crucial for the decision-making process for re-revision at an early stage.

Tetracycline hydrochloride-containing poly (ε-caprolactone)/poly lactic acid scaffold for bone tissue engineering application: in vitro and in vivo study

In the current study, tetracycline hydrochloride (TCH), an antibiotic against most of the medically relevant bacteria, was incorporated into poly (ε-caprolactone)/poly lactic acid solution in order to develop a composite scaffold with both antibacterial and osteoinductive properties for the repair of infected bone defects. The composite scaffolds were produced from poly (ε-caprolactone) (PCL) and poly lactic acid (PLA) solution (1:1 (w/w)) incorporated with 3, 5, and 10% (w/w) of TCH by thermally induced phase separation technique. The scaffolds were evaluated regarding their morphology, wettability, porosity, degradation, mechanical properties, and cellular response. The scaffold containing 10% of TCH (PCL/PLA/TCH10%) was chosen as the optimum scaffold for further investigation in a rat femoral defect model. The study showed that after eight weeks, the bone formation was relatively higher in PCL/PLA/TCH10%-treated group with completely filled defect when compared with control (PCL/PLA scaffold without TCH). Histopathological evaluation showed that the defect in PCL/PLA/TCH10%-treated group was fully replaced by new bone and connective tissue. Our results provide evidence supporting the possible applicability of TCH-containing scaffolds for successful bone regeneration.

Bone tissue engineering via growth factor delivery: from scaffolds to complex matrices.

In recent years, bone tissue engineering has emerged as a promising solution to the limitations of current gold standard treatment options for bone related-disorders such as bone grafts. Bone tissue engineering provides a scaffold design that mimics the extracellular matrix, providing an architecture that guides the natural bone regeneration process. During this period, a new generation of bone tissue engineering scaffolds has been designed and characterized that explores the incorporation of signaling molecules in order to enhance cell recruitment and ingress into the scaffold, as well as osteogenic differentiation and angiogenesis, each of which is crucial to successful bone regeneration. Here, we outline and critically analyze key characteristics of successful bone tissue engineering scaffolds. We also explore candidate materials used to fabricate these scaffolds. Different growth factors involved in the highly coordinated process of bone repair are discussed, and the key requirements of a growth factor delivery system are described. Finally, we concentrate on an analysis of scaffold-based growth factor delivery strategies found in the recent literature. In particular, the incorporation of two-phase systems consisting of growth factor-loaded nanoparticles embedded into scaffolds shows great promise, both by providing sustained release over a therapeutically relevant timeframe and the potential to sequentially deliver multiple growth factors.