Dataset Information

Effect of Bifunctional ? Defensin 2-Modified Scaffold on Bone Defect Reconstruction.

ABSTRACT: Bone tissue engineering has emerged as an effective alternative treatment to the problem of bone defect. To repair a bone defect, antibiosis and osteogenesis are two essential aspects of the repair process. By searching the literature and performing exploratory experiments, we found that ? defensin 2 (BD2), with bifunctional properties of antibiosis and osteogenesis, was a feasible alternative for traditional growth factors. The antimicrobial ability of BD2 against Staphylococcus aureus and Escherichia coli was studied by the spread plate and live/dead staining methods (low effective concentration of 20 ng/mL). BD2 was also demonstrated to enhance osteogenesis, with higher messenger RNA (mRNA) and protein expression of the osteogenic markers collagen I (Col1), runt-related transcription factor 2 (Runx2), osteopontin (Opn), and osteocalcin (Ocn) in vitro (1.5-2.5-fold increase compared with the control group in the most effective concentration group), which was consistent with the alkaline phosphatase (ALP) and alizarin red S (ARS) staining results. We implanted poly(sebacoyl diglyceride) (PSeD) combined with BD2 and rat bone tissue-derived mesenchymal stem cells (rBMSCs) under the back skin of rats and found that the inflammatory response was significantly lower with this combination than with the PSeD/rBMSCs scaffold without BD2 and the pure PSeD group and was similar to the control group. Importantly, when assessed in a critical-sized in vivo rat 8 m diameter calvaria defect model, a scaffold we developed combining bifunctional BD2 with porous organic polymer displayed an osteogenic effect that was 160-200% greater than the control group. The in vivo study results revealed a significant osteogenic response and antimicrobial effect and were consistent with the in vitro results. In summary, BD2 displayed a great potential of simultaneously promoting bone regeneration and preventing infection and could provide a viable alternative to traditional growth factors applied in bone defect repair.

SUBMITTER: Peng Y

PROVIDER: S-EPMC7057706 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Effect of Bifunctional β Defensin 2-Modified Scaffold on Bone Defect Reconstruction.

Peng Yiyu Y Li Lunhao L Yuan Qingyue Q Gu Ping P You Zhengwei Z Zhuang Ai A Bi Xiaoping X

ACS omega 20200218 8

Bone tissue engineering has emerged as an effective alternative treatment to the problem of bone defect. To repair a bone defect, antibiosis and osteogenesis are two essential aspects of the repair process. By searching the literature and performing exploratory experiments, we found that β defensin 2 (BD2), with bifunctional properties of antibiosis and osteogenesis, was a feasible alternative for traditional growth factors. The antimicrobial ability of BD2 against <i>Staphylococcus aureus</i> a ...[more]

PMID: 32149260

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Project description:Osteochondral defects of the knee are common in orthopaedic patients. They are challenging to treat, especially in young, highly demanding patients who do not qualify for arthroplasty. Among the many possibilities to treat osteochondral lesions presented so far, none is ideal. Because of the poor healing potential of cartilage, treatment outcomes significantly worsen with larger lesions. The treatment of large defects usually requires expensive solutions, sometimes including second-stage surgery. Using mesenchymal stem cell transplantation and cancellous bone autografts, the technique presented here for osteochondral lesion reconstruction can be effectively used to treat large osteochondral lesions in a single-stage procedure. Technique Video Video 1 Osteochondral lesion reconstruction using mesenchymal stem cell transplantation and cancellous bone autografts; right knee. Patients are considered candidates after careful selection. To promote mesenchymal stem cell growth, 4 days before surgery, patients are administered granulocyte colony-stimulating factor. On the day of surgery, the mesenchymal stem cell suspension is obtained, using an MSC blood separator, under the control of the blood bank. A cytometric test is performed for the quantitative evaluation of cell lines, as well as a histopathological evaluation of stained preparations. The cell suspension is then transferred to the operating theater. The diagnosis is confirmed arthroscopically through a standard anterolateral portal, and concomitant lesions are excluded. Mini-open access is created next to the site of the lesion. After the lesion is exposed, delaminated cartilage or bony-cartilage sequestrum is removed. Using a bone spoon, the bony edges of the cavity are resected to healthy cartilaginous tissue. The next step is decortication and debridement of the bottom. To ensure the integration of bone grafts, it is necessary to remove the sclerotic subchondral bone layer until bleeding from the bone occurs. An additional factor improving the blood supply is the microfracturing the bottom of the cavity. From a separate site above the iliac crest, autologous cancellous bone grafts are harvested. The bottom of the lesion is filled with the debris of the cancellous bone. Restoration with a bone graft is performed up to the height of the surrounding healthy bone margin. During this time, the previously sized collagen sponge Tachosil is soaked in MSC suspension. The sponge is placed on the lesion and adjusted to the edges of the lesion using tweezers. The soaked implant should not cover surrounding healthy cartilage edges, but only fill the cavity. The entirety of the damaged fragment is covered with a 2-component fibrin glue. After binding, a suspension of mesenchymal cells, is administered under the fibrin layer using a no. 12 needle, and the application site is sealed with the rest of the glue. The wound is closed with layered sutures and sealed with sterile dressing. The operated joint is protected by cocoon dressing to limit mobility in the early postoperative period.

Project description:IntroductionReconstruction of critical bone defects is challenging. In a substantial subgroup of patients, conventional reconstructive techniques are insufficient. Biodegradable scaffolds have emerged as a novel tissue engineering strategy for critical-sized bone defect reconstruction. A corticoperiosteal flap integrates the hosts' ability to regenerate bone and permits the creation of a vascular axis for scaffold neo-vascularisation (regenerative matching axial vascularisation-RMAV). This phase IIa study evaluates the application of the RMAV approach alongside a custom medical-grade polycaprolactone-tricalcium phosphate (mPCL-TCP) scaffold (Osteopore) to regenerate bone sufficient to heal critical size defects in lower limb defects.Methods and analysisThis open-label, single-arm feasibility trial will be jointly coordinated by the Complex Lower Limb Clinic (CLLC) at the Princess Alexandra Hospital in Woolloongabba (Queensland, Australia), the Australian Centre for Complex Integrated Surgical Solutions (Queensland, Australia) and the Faculty of Engineering, Queensland University of Technology in Kelvin Grove (Queensland, Australia). Aiming for limb salvage, the study population (n=10) includes any patient referred to the CLLC with a critical-sized bone defect not amenable to conventional reconstructive approaches, after discussion by the interdisciplinary team. All patients will receive treatment using the RMAV approach using a custom mPCL-TCP implant. The primary study endpoint will be safety and tolerability of the reconstruction. Secondary end points include time to bone union and weight-bearing status on the treated limb. Results of this trial will help shape the role of scaffold-guided bone regenerative approaches in complex lower limb reconstruction where current options remain limited.Ethics and disseminationApproval was obtained from the Human Research Ethics Committee at the participating centre. Results will be submitted for publication in a peer-reviewed journal.Trial registration numberACTRN12620001007921.

Dataset Information

Effect of Bifunctional ? Defensin 2-Modified Scaffold on Bone Defect Reconstruction.

Publications

Effect of Bifunctional β Defensin 2-Modified Scaffold on Bone Defect Reconstruction.

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