Critical-Size Bone Defects: Is There a Consensus for Diagnosis and Treatment?

Nauth, Aaron; Schemitsch, Emil H.; Norris, Brent; Nollin, Zachary; Watson, John T.

doi:10.1097/bot.0000000000001115

Cited by 239 publications

(200 citation statements)

References 26 publications

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“…Bone healing is a well-orchestrated process and for most minor fractures a mechanical fixation of the damaged bone region is sufficient for successful convalescence. However, if a defect reaches a critical size (~≥2.5 cm (Schemitsch, 2017 ; Nauth et al, 2018 ), depending on the surgical case), the endogenous regenerative capacity of bone tissue is insufficient for self-repair (Mothersill et al, 1991 ). Critical size bone defects caused by diseases such as osteogenesis imperfecta, osteoarthritis, osteomyelitis, osteoporosis, or conditions related to infection or induced by wear, still remain key challenges to be addressed in clinical practice (Porter et al, 2009 ; Nauth et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Polymer-Bioactive Glass Composite Filaments for 3D Scaffold Manufacturing by Fused Deposition Modeling: Fabrication and Characterization

Distler

Fournier

Grünewald

et al. 2020

Front. Bioeng. Biotechnol.

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Critical size bone defects are regularly treated by auto-and allograft transplantation. However, such treatments require to harvest bone from patient donor sites, with often limited tissue availability or risk of donor site morbidity. Not requiring bone donation, three-dimensionally (3D) printed implants and biomaterial-based tissue engineering (TE) strategies promise to be the next generation therapies for bone regeneration. We present here polylactic acid (PLA)-bioactive glass (BG) composite scaffolds manufactured by fused deposition modeling (FDM), involving the fabrication of PLA-BG composite filaments which are used to 3D print controlled open-porous and osteoinductive scaffolds. We demonstrated the printability of PLA-BG filaments as well as the bioactivity and cytocompatibility of PLA-BG scaffolds using pre-osteoblast MC3T3E1 cells. Gene expression analyses indicated the beneficial impact of BG inclusions in FDM scaffolds regarding osteoinduction, as BG inclusions lead to increased osteogenic differentiation of human adipose-derived stem cells in comparison to pristine PLA. Our findings confirm that FDM is a convenient additive manufacturing technology to develop PLA-BG composite scaffolds suitable for bone tissue engineering.

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Section: Introductionmentioning

confidence: 99%

Polymer-Bioactive Glass Composite Filaments for 3D Scaffold Manufacturing by Fused Deposition Modeling: Fabrication and Characterization

Distler

Fournier

Grünewald

et al. 2020

Front. Bioeng. Biotechnol.

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“…In humans, critical-sized defects can result from severe trauma, blast injuries, and large scale bone resection due to infection or tumors (Schemitsch, 2017). Some physiological factors that enhance the risk of non-unions include diabetes, obesity, inflammatory arthritis, and hypothyroidism (Nauth et al, 2018; Roddy et al, 2018). Orthopedic repair of critical-sized defects generally requires an invasive procedure that may include autologous or allogeneic bone grafting (Polo-Corrales et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Decellularized Adipose Tissue Hydrogel Promotes Bone Regeneration in Critical-Sized Mouse Femoral Defect Model

Mohiuddin

Campbell

Poche

et al. 2019

Front. Bioeng. Biotechnol.

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Critical-sized bone defects fail to heal and often cause non-union. Standard treatments employ autologous bone grafting, which can cause donor tissue loss/pain. Although several scaffold types can enhance bone regeneration, multiple factors limit their level of success. To address this issue, this study evaluated a novel decellularized human adipose tissue (DAT) hydrogel as an alternative. In this study, DAT hydrogel alone, or in combination with adipose-derived stromal/stem cells (ASC), osteo-induced ASCs (OIASC), and hydroxyapatite were tested for their ability to mediate repair of a critical-sized (3 mm) femoral defect created in C57BL/6 mice. Micro-computed tomography results showed that all DAT hydrogel treated groups significantly enhanced bone regeneration, with OIASC + hydroxyapatite treated group displaying the most robust bone regeneration. Histological analyses revealed that all treatments resulted in significantly higher tissue areas with the relative mineralized tissue area significantly increased at 12 weeks; however, cartilaginous content was lowest among treatment groups with OIASC. Immunohistochemical analyses showed that DAT hydrogel enhanced collagen I and osteopontin expression, while the addition of OIASCs to the hydrogel reduced collagen II levels. Thus, DAT hydrogel promotes bone regeneration in a critical-sized femoral defect model that is further enhanced in the presence of OIASCs and hydroxyapatite.

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“…Trauma, tumor resection, bone infection, and regenerative disorder-caused bone defects are a challenge to the medical fraternity. 1 − 4 Autograft and allograft transplantations are the common methods applied by surgeons to treat bone defects; however, limited bone sources and immunological reactions are still a cause for worry. 4 − 6 Therefore, surgeons have long been interested in taking advantage of the properties of various metals for the reconstruction of bone defects.…”

Section: Introductionmentioning

confidence: 99%

Three-Dimensional, MultiScale, and Interconnected Trabecular Bone Mimic Porous Tantalum Scaffold for Bone Tissue Engineering

et al. 2020

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To investigate the biocompatibility and bone ingrowth properties of a novel trabecular bone mimic porous tantalum scaffold which holds potential for bone tissue engineering, a novel three-dimensional, multiscale interconnected porous tantalum scaffold was designed and manufactured. The morphology of the novel scaffold was observed with the use of scanning electron microscopy (SEM) and industrial computerized tomography. Mesenchymal stem cells (MSCs) were cultured with novel porous tantalum powder, SEM was carried out for the observation of cell morphology and adhesion, and cytotoxicity was evaluated by the MTT assay. Canine femoral shaft bone defect models were established, and novel porous tantalum rods were used to repair the bone defect. Repair effects and bone integration were evaluated by hard tissue slice examination and push-out tests at the indicated time. We found that the novel porous tantalum scaffold is a trabecular bone mimic, having the characteristics of being three-dimensional, multiscaled, and interconnected. The MSCs adhered to the surface of tantalum and proliferated with time, the tantalum extract did not have a cytotoxic effect on MSCs. In the bone defect model, porous tantalum rods integrated tightly with the host bone, and new bone formation was found on the scaffold-host bone interface both 3 and 6 months after the implantation. Favorable bone ingrowth was observed in the center of the tantalum rod. The push-out test showed that the strength needed to push out the tantalum rod is comparable for both 3 and 6 months when compared with the normal femoral shaft bone tissue. These findings suggested that the novel trabecular bone mimic porous tantalum scaffold is biocompatible and osteoinductive, which holds potential for bone tissue engineering application.

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Critical-Size Bone Defects: Is There a Consensus for Diagnosis and Treatment?

Cited by 239 publications

References 26 publications

Polymer-Bioactive Glass Composite Filaments for 3D Scaffold Manufacturing by Fused Deposition Modeling: Fabrication and Characterization

Polymer-Bioactive Glass Composite Filaments for 3D Scaffold Manufacturing by Fused Deposition Modeling: Fabrication and Characterization

Decellularized Adipose Tissue Hydrogel Promotes Bone Regeneration in Critical-Sized Mouse Femoral Defect Model

Three-Dimensional, MultiScale, and Interconnected Trabecular Bone Mimic Porous Tantalum Scaffold for Bone Tissue Engineering

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