Development of a novel minimally invasive technique to washout necrotic bone marrow content from epiphyseal bone: A preliminary cadaveric bone study

Monte, Felipe; Park, Min Sung; Gokani, Vishal; Singhal, Mohit; Ma, Chi; Aruwajoye, Olumide; Niese, Brad; Liu, Xiaohua; Kim, Harry K.W.

doi:10.1016/j.otsr.2020.01.006

Cited by 6 publications

(16 citation statements)

References 20 publications

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“…11 More importantly, MED drilling tunnels can be used as in ow and out ow portals for the intraosseous saline wash. Our previous study reported that the bone wash following the MED can signi cantly remove debris in the necrotic bone marrow space such as fats, DNA fragments, and pro-in ammatory proteins. 29,33 As a result, the washed epiphyseal bone provides a "porous scaffold" facilitating new tissue ingrowth and angiogenesis. Our previous study also revealed that the bone wash process could signi cantly improve bone regeneration following ONFH, as compared with the MED drillings or with no treatment on the piglet LCPD model.…”

Section: Discussionmentioning

confidence: 99%

“…28 Furthermore, we recently developed a bone wash technique to remove necrotic bone marrow and debris from the necrotic area. 29 It is postulated that a local necrotic bone wash may better facilitate the delivery of injectable biomaterials. Moreover, we previously reported a heparin-modi ed gelatin molecule could speci cally bind to bioactive proteins of the transforming growth factor beta family, involving BMP2 and VEGF.…”

Section: Introductionmentioning

confidence: 99%

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Local Administration of Bone Morphogenetic Protein-2 Using a Hydrogel Carrier for Robust Bone Regeneration in a Large Animal Model of Legg-Calvé-Perthes disease

Kim

Park

et al. 2023

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Legg-Calvé-Perthes disease is juvenile idiopathic osteonecrosis of the femoral head (ONFH) that has no effective clinical resolutions. Previously, local injection of bone morphogenetic protein-2 (BMP2) for ONFH treatment showed a heterogeneous bone repair and a high incidence of heterotopic ossification (HO) due to the BMP2 leakage. Here, we developed a BMP2-hydrogel treatment via a transphyseal bone wash and subsequential injection of BMP2-loaded hydrogel. In vivo studies showed that a hydrogel of gelatin-heparin-tyramine retained the BMP2 for four weeks. The injection of the hydrogel can efficiently prevent leakage. With the bone wash, the injected hydrogel had a broad distribution in the head. In vivo studies on pigs revealed that the BMP2-hydrogel treatment produced a homogeneous bone regeneration without HO. It preserved the subchondral contour and restored the subchondral endochondral ossification, although it increased growth plate fusions. In summary, the study demonstrated a promising BMP2-hydrogel treatment for ONFH treatment, especially for teenagers.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Local Administration of Bone Morphogenetic Protein-2 Using a Hydrogel Carrier for Robust Bone Regeneration in a Large Animal Model of Legg-Calvé-Perthes disease

Kim

Park

et al. 2023

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“…9,10 Recently, a minimally invasive technique was developed to wash out the necrotic bone marrow as a treatment for AVN. 11 This technique involves the placement of intraosseous needles, which are used to infuse and collect the saline wash solution. It showed that saline wash could remove soluble debris, such as DNA fragments and proteins.…”

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Ex vivo study of detergent‐assisted intraosseous bone wash treatment of osteonecrosis

Andre

Boschetto

Gokani

et al. 2022

Journal Orthopaedic Research

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Avascular necrosis (AVN) involves ischemic cell death of the bone. AVN leaves an abundance of necrotic lipids and debris in the bone marrow, which instigates inflammatory bone repair. Consequently, the necrotic bone microenvironment stimulates excessive bone resorption, leading to joint deformities and osteoarthritis.Here, we performed a detergent-assisted bone wash using poloxamer 407 (P407) to clean the necrotic bone environment by removing lipids and necrotic debris. The new concept was tested using an established ex vivo AVN model of porcine cadaver humeral heads. The P407 wash was performed using P407 solution and followed with saline via two intraosseous needles. Visual inspection and image analyses of average pixel light intensity showed that the P407 wash produced a better-cleaned bone than the saline wash. Analyses of the collected bone wash solution showed a two-fold increase in triglycerides (101 vs. 53 mmol/head, p = 0.006) and a 10-fold increase in the dry weight of the removed debris (1.34 vs. 0.13 g/head, p = 0.02) with the P407 wash compared to saline. The histological evaluation showed significantly decreased Oil-Red-O (fats) staining in the P407-washed bone compared with the saline-washed bone. The in vitro assays of Alizarin red and qPCR showed the P407 wash neither altered the osteogenic behaviors of porcine bone marrow-derived mesenchymal cells (pBMMCs) nor raised inflammatory responses of porcine bone marrow-derived macrophages (pBMMs). In conclusion, detergent-assisted bone wash using P407 produced a better removal of nonsoluble debris from the bone marrow space than the saline wash without causing changes to osteogenesis or inflammatory reactions.avascular necrosis, intraosseous bone wash, poloxamer 407 | INTRODUCTIONAvascular necrosis (AVN) is the death of bone, commonly affecting the hip, shoulder, and knee joints. [1][2][3] The annual incidence of hip AVN in the United States is about 10,000-20,000 per year, 4 and over 20 million people in the world will suffer from AVN in the next 10 years. 5 Without treatment, over 50% of the affected joints will develop severe disabling osteoarthritis, 2,6,7 which significantly reduces the quality of life. Total joint replacement (TJR) is often required due to AVN progression, but TJR is a suboptimal treatment

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“…Thus, we developed a minimally invasive multi-needle procedure to flush out the necrotic debris and inflammatory molecules from the femoral head 10 . The feasibility of the procedure was confirmed recently in a cadaver bone study 10 ; however, the in vivo effects of the procedure are unknown. The purpose of this study was to determine the effects of flushing out the necrotic cell debris and inflammatory proteins on bone repair in an immature pig model of ischemic osteonecrosis.…”

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confidence: 99%

“…At present, there is no clinically applicable, nondestructive method to remove the necrotic debris and inflammatory molecules from the femoral head. Thus, we developed a minimally invasive multi-needle procedure to flush out the necrotic debris and inflammatory molecules from the femoral head 10 . The feasibility of the procedure was confirmed recently in a cadaver bone study 10 ; however, the in vivo effects of the procedure are unknown.…”

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confidence: 99%

Minimally Invasive Necrotic Bone Washing Improves Bone Healing After Femoral Head Ischemic Osteonecrosis

Kim

Park

Monte

et al. 2021

Journal of Bone and Joint Surgery

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Background: Ischemic osteonecrosis of the femoral head produces necrotic cell debris and inflammatory molecules in the marrow space, which elicit a chronic inflammatory repair response. The purpose of this study was to determine the effects of flushing out the necrotic cell debris and inflammatory proteins on bone repair in a piglet model of ischemic osteonecrosis.Methods: Osteonecrosis of the femoral head of the right hindlimb was induced in 12 piglets by tying a ligature tightly around the femoral neck. One week after the surgery, 6 animals were treated with a percutaneous 3-needle bone washing procedure and non-weight-bearing (NWB) of the right hindlimb (wash group). The total saline solution wash volume was 450 mL per femoral head. Serial wash solutions were collected and analyzed. The remaining 6 animals were treated with NWB only (NWB group). At 8 weeks after the surgery, the femoral heads were assessed using radiography, microcomputed tomography (micro-CT), and histological analysis. In addition, we compared the results for these piglets with our published results for 6 piglets treated with multiple epiphyseal drilling (MED) plus NWB without bone washing (MED group).Results: Necrotic cells and inflammatory proteins were present in the bone wash solution collected 1 week after ischemia induction. The protein and triglyceride concentrations decreased significantly with subsequent washing (p < 0.005). At 8 weeks after ischemia induction, the wash group had a significantly higher bone volume than the MED or NWB group (p < 0.0001). Histological bone-formation measures were also significantly increased in the wash group compared with the MED group (p = 0.002) or NWB group (p < 0.0001) while macrophage numbers were significantly decreased in the wash group. Conclusions:The percutaneous 3-needle procedure flushed out cell debris and inflammatory proteins from the necrotic femoral heads, decreased osteoclasts and macrophages, and increased bone formation following induction of ischemic osteonecrosis.Clinical Relevance: We believe that this is the first study to investigate the concept of washing out the necrotic femoral head to improve bone healing. The minimally invasive procedure may be useful to improve the necrotic bone environment and bone repair following ischemic osteonecrosis. Juvenile ischemic osteonecrosis of the femoral head results from a disruption of blood flow to the growing femoral head that produces extensive ischemic cell death in the bone marrow and the trabecular bone. The dying cells are known to release endogenous inflammatory factors called damage-associated molecular patterns (DAMPs), which alert the immune cells of tissue damage. The DAMPs trigger the recruitment of innate immune cells and the production of pro-inflammatory cytokines and chemokines 1,2 . High mobility group box-1 (HMGB1) protein is a prototypical DAMP that normally functions as a chromatin-Disclosure: The authors indicated that no external funding was received for any aspect of this work. On the Disclosure of Potential Conf...

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Development of a novel minimally invasive technique to washout necrotic bone marrow content from epiphyseal bone: A preliminary cadaveric bone study

Cited by 6 publications

References 20 publications

Local Administration of Bone Morphogenetic Protein-2 Using a Hydrogel Carrier for Robust Bone Regeneration in a Large Animal Model of Legg-Calvé-Perthes disease

Local Administration of Bone Morphogenetic Protein-2 Using a Hydrogel Carrier for Robust Bone Regeneration in a Large Animal Model of Legg-Calvé-Perthes disease

Ex vivo study of detergent‐assisted intraosseous bone wash treatment of osteonecrosis

Minimally Invasive Necrotic Bone Washing Improves Bone Healing After Femoral Head Ischemic Osteonecrosis

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