Autologous Bone Marrow Aspirate Research Articles

A Comparative Quantification in Cellularity of Bone Marrow Aspirated with two New Harvesting Devices, and The Non-equivalent Difference Between A Centrifugated Bone Marrow Concentrate And A Bone Marrow Aspirate As Biological Injectates, Using A Bi-Lateral Patient Model

The first aim of this study was to examine the cellularity and quality of autologous bone marrow aspirates harvested with two novel FDA-cleared devices, namely the Aspire™ bone marrow aspiration system (AS-BMAS) and the Marrow Cellution bone marrow aspiration device (MC-BMAD). Compared to traditional bone marrow harvesting needle systems, both these devices have a closed distal tip, avoiding preferential marrow collection (peripheral blood aspiration) from deeper cavity regions, whereas the side holes facilitate more horizontal marrow extraction. In all patients, a similar harvesting technique was used. The second aim was to demonstrate the effectiveness of mechanical centrifugation of a large volume of extracted bone marrow to produce a bone marrow concentrate (BMC). Finally, we directly compared bone marrow constituents aspirated with MC-BMAD with a BMC, generated by centrifugation of bone marrow harvested using the AS-BMAS. A bi-lateral patient model was used for all comparisons. All cellular analyses included the measurement of Colony-Forming Units-fibroblasts (CFU/f) levels, CD34+cells/ml, Total Nucleated Cells (TNCs)/ml, platelets/ml, and Red Blood Cells (RBCs)/ml in a single, FDA-approved laboratory, compliant with Good Manufacturing Practice regulations. A total of 12 patients consented to the study. In the direct BMA comparison, the AS-BMAS bone marrow yielded significantly higher CFU/f counts and TNC concentrations than the MC-BMAD (1,060/ml, 33.5 × 106/ml, and 610/ml and 28.6 × 106/ml, respectively), with comparable platelet and RBC concentrations. Data following BMA concentration to produce a BMC revealed highly significant cell yields, fewer RBCs, and lower hematocrit (HCT). A direct cellular comparison between the aspirate of the MCBMAD and centrifugated BMC following AS-BMAS marrow extraction showed highly significant differences in cellularity. The AS-BMAS produced cell concentrations of CFU/f, CD34+ cells, TNCs, platelets, and RBCs that were comparable, or greater than, the predicate device. We believe that concentrating bone marrow is a consistent and safe method to produce a BMC that has the potential to be clinically effective. Furthermore, data indicate a non-equivalent difference in BMC cellularity, when compared to a non-filtered and non-centrifugated BMA for clinical use.

Cellular and Clinical Analyses of Autologous Bone Marrow Aspirate Injectate for Knee Osteoarthritis: A Pilot Study.

Knee osteoarthritis (OA) is characterized by pain and functional deficits. Common conservative strategies include medications, physical therapy, and intra-articular injections. Recently, treatment using autologous cell injections has increased. To characterize the cellular content of bone marrow aspirate (BMA) and to evaluate the effect of intra-articular autologous BMA injections in patients with mild knee OA. Prospective pilot observational study. Academic institution. Eleven patients with unilateral or bilateral mild knee OA (15 knees) were included in the cellular analysis. Ten patients (13 knees) were included in the overall (cellular and clinical) analysis. BMA was aspirated from patients' iliac crests and then injected intra-articularly under fluoroscopic and/or ultrasound guidance. BMA samples were analyzed using flow cytometry, colony forming unit (CFU) assays, and enzyme-linked immunosorbent assays. Questionnaires assessing pain and function were administered preinjection and at 1, 3, 6, and 12 months postinjection. Side effects and satisfaction were assessed. Total nucleated cell (TNC) concentration, mesenchymal stem cell (MSC) concentration, CFU count, and interleukin-1 receptor antagonist (IL-1Ra) concentration. BMA sample analyses revealed wide ranges in TNC concentration (173300-4 491 050 cells/mL), MSC concentration (0-500 cells/mL), CFUs (0-19), and IL-1Ra concentration (2806-29 394 pg/mL). Improvements in Knee Injury and Osteoarthritis Outcomes Score for Joint Replacement were observed throughout the 12-month follow-up period (F[4,12] = 12.29, P < .001). Additionally, current, usual, best, and worst numerical rating scale pain scores significantly decreased over time (P < .001). Patient satisfaction was high (range: 8.1 ± 2.1-8.8 ± 1.9), and side effects were uncommon. The cellular content of BMA samples varied widely between patients and was lower than the anticipated yield reported by the device's manufacturer. However, intra-articular BMA injections for knee OA in a small pilot cohort appeared to be safe with potential therapeutic value. Larger, prospective, double-blinded studies are warranted.

Human mesenchymal stem cells respond differentially to platelet preparations and synthesize hyaluronic acid in nucleus pulposus extracellular matrix

BACKGROUND CONTEXTIn recent years, autologous platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) have been used as treatments for disc-related pain. A better understanding of the effects of leukocyte-rich (LR) versus leukocyte poor (LP-) PRP on bone marrow derived human mesenchymal stem/progenitor cells (hMSCs) is likely to improve future research studies, clinical practice and care for patients with chronic discogenic back pain. PURPOSEThe primary aim of this study is to determine the effects of LR-PRP and LP-PRP on the proliferation and migration of hMSCs in pig nucleus pulposus (NP) extracellular matrix (ECM). The secondary aim is to characterize hMSC-dependent expression of the matrix remodeling enzymes metalloproteinases MMP-2, MMP-3, MMP-9 and tissue inhibitor of metalloproteinases TIMP-2, and to determine whether transplanted hMSCs can synthesize hyaluronic acid (HA). STUDY DESIGNControlled laboratory study. METHODSBone marrow-derived culture expanded hMSCs were seeded onto pig NP and cultured with LR-PRP, LP-PRP or serum/platelet releasate (PR). The same conditions without hMSCs were used as controls. hMSC proliferation, migration and dispersion was assessed via fluorescent microscopy, while HA synthesis, MMP-2, MMP-3, MMP-9, and TIMP-2 protein levels were assessed via enzyme linked immunosorbent assay. All funding was provided by a 501c(3) research foundation and does not have any commercial or sponsorship interests. RESULTSLP-PRP and PR cultures resulted in higher hMSC proliferation, migration, dispersion, and MMP-2 expression. LP-PRP cultures resulted in the highest HA production. LR-PRP cultures resulted in lower hMSC proliferation, negligible migration and dispersion, increased MMP-9 expression and lower HA production. CONCLUSIONSHuman bone marrow-derived hMSCs seeded onto pig NP ECM are capable of synthesizing HA, indicating a transition towards a NP cell phenotype. This process was most enhanced by LP-PRP and marked by increased hMSC proliferation, MMP-2 production, HA synthesis and reduced MMP-9 levels. CLINICAL SIGNIFICANCELP-PRP and PR, with or without hMSCs, may provide better outcomes than LR-PRP in lab investigations and clinical trials for discogenic pain. Bone marrow-derived hMSCs may hold promise as a treatment for disc degeneration.

Bone Marrow Aspirate Concentrate Is Equivalent to Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis at 1 Year: A Prospective, Randomized Trial.

Background:Approximately 47 million people in the United States have been diagnosed with arthritis. Autologous platelet-rich plasma (PRP) injections have been documented to alleviate symptoms related to knee osteoarthritis (OA) in randomized controlled trials, systematic reviews, and meta-analyses. Autologous bone marrow aspirate concentrate (BMC) injections have also emerged as a treatment option for knee OA, with a limited clinical evidence base.Purpose:To compare the efficacy of BMC to PRP for the treatment of knee OA regarding pain and function at multiple time points up to 12 months after an injection. We hypothesized that BMC will be more effective in improving outcomes in patients with knee OA.Study Design:Randomized controlled trial; Level of evidence, 2Methods:A total of 90 participants aged between 18 and 80 years with symptomatic knee OA (Kellgren-Lawrence grades 1-3) were randomized into 2 study groups: PRP and BMC. Both groups completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and subjective International Knee Documentation Committee (IKDC) questionnaires before and 1, 3, 6, 9, and 12 months after a single intra-articular injection of leukocyte-rich PRP or BMC.Results:There were no statistically significant differences in baseline IKDC or WOMAC scores between the 2 groups. All IKDC and WOMAC scores for both the PRP and BMC groups significantly improved from baseline to 1 month after the injection (P < .001). These improvements were sustained for 12 months after the injection, with no difference between PRP and BMC at any time point.Conclusion:Both PRP and BMC were effective in improving patient-reported outcomes in patients with mild to moderate knee OA for at least 12 months; neither treatment provided a superior clinical benefit. Autologous PRP and BMC showed promising clinical potential as therapeutic agents for the treatment of OA, and while PRP has strong clinical evidence to support its efficacy, BMC has limited support. This study did not prove BMC to be superior to PRP, providing guidance to clinicians treating OA. It is possible that the results were affected by patients knowing that there was no control group.Registration:NCT03289416 (ClinicalTrials.gov identifier).

Autologous bone marrow aspirates in the treatment of extensive purulent wounds

Autologous bone marrow aspirates in the treatment of extensive purulent wounds

Colony Formation, Migratory, and Differentiation Characteristics of Multipotential Stromal Cells (MSCs) from "Clinically Accessible" Human Periosteum Compared to Donor-Matched Bone Marrow MSCs.

Periosteum is vital for fracture healing, as a highly vascular and multipotential stromal cell- (MSC-) rich tissue. During surgical bone reconstruction, small fragments of periosteum can be “clinically accessible,” yet periosteum is currently not ultilised, unlike autologous bone marrow (BM) aspirate. This study is aimed at comparing human periosteum and donor-matched iliac crest BM MSC content and characterising MSCs in terms of colony formation, growth kinetics, phenotype, cell migration patterns, and trilineage differentiation capacity. “Clinically accessible” periosteum had an intact outer fibrous layer, containing CD271+ candidate MSCs located perivasculary; the inner cambium was rarely present. Following enzymatic release of cells, periosteum formed significantly smaller fibroblastic colonies compared to BM (6.1 mm2 vs. 15.5 mm2, n = 4, P = 0.0006). Periosteal colonies were more homogenous in size (range 2-30 mm2 vs. 2-54 mm2) and on average 2500-fold more frequent (2.0% vs. 0.0008%, n = 10, P = 0.004) relative to total viable cells. When expanded in vitro, similar growth rates up to passage 0 (P0) were seen (1.8 population doublings (PDs) per day (periosteum), 1.6 PDs per day (BM)); however, subsequently BM MSCs proliferated significantly slower by P4 (4.3 PDs per day (periosteum) vs. 9.3 PDs per day (BM), n = 9, P = 0.02). In early culture, periosteum cells were less migratory at slower speeds than BM cells. Both MSC types exhibited MSC phenotype and trilineage differentiation capacity; however, periosteum MSCs showed significantly lower (2.7-fold) adipogenic potential based on Nile red : DAPI ratios with reduced expression of adipogenesis-related transcripts PPAR-γ. Altogether, these data revealed that “clinically accessible” periosteal samples represent a consistently rich source of highly proliferative MSCs compared to donor-matched BM, which importantly show similar osteochondral capacity and lower adipogenic potential. Live cell tracking allowed determination of unique morphological and migration characteristics of periosteal MSCs that can be used for the development of novel bone graft substitutes to be preferentially repopulated by these cells.

MORPHOLOGICAL ASSESSMENT OF STRUCTURAL CHANGES IN KNEE JOIN IN MODELED OSTEOARTHROSIS AND APPLICATION OF AUTOLOGICAL BONE MARROW ASPIRATE

Background. Treatment of knee join osteoarthritis is one of challenging medico-social issues. Sometimes the conservative treatment fails to produce therapeutic effect, therefore, the use of cellular technologies in the treatment for progressive degenerative changes of the knee joint has been proposed. The objective of this study was to investigate the effect of bone marrow aspirate on the structural changes in the knee joint in modelled osteoarthritis. Materials and methods. The experimental osteoarthritis was simulated in rabbits. Autologous bone marrow aspirate was injected into the knee cavity in 1 month after surgery, and then in 2, 5 months the structural changes of the capsule, meniscus, proximal epiphysis of the tibia were studied. Results. There were the following structural changes in the capsule of the knee joint: stratification of structural elements and reduction of the cell density of the capsule, cell necrosis of the inner surface of the capsule. The defect area of the epiphyseal cartilage was lacking in cartilage, and the peripheral cartilage thickness was decreased by 30, 4% (p&lt;0,05); subchondral bone density made up an average 55,9% compared with the control. In the group with bone marrow aspirate, the density of fibroblasts in the joint capsule increased and the surface of the meniscus was partially preserved; the density of subchondral bone tissue was significantly higher by 79,5% (p&lt;0.05) compared with the control. Structural changes in osteoarthritis include progressive dystrophic changes of the joint surface, subchondral bone, meniscus, and joint capsule. The use of autologous bone marrow aspirate can prevent damage to the subchondral bone, meniscus and joint capsule and promote reticular tissue formation and induction of angiogenesis. The morphological changes of bone marrow through progressive osteoarthritis and its renovation after local application of autological bone marrow aspirate concentrate are promising approaches for the further studies.

Treatment of atrophic non-union fractures by autologous bone marrow aspirate injections: A prospective study

Treatment of atrophic non-union fractures by autologous bone marrow aspirate injections: A prospective study

Ten-year results of concentrated autologous bone marrow aspirate transplantation for osteonecrosis of the femoral head: a retrospective study

BackgroundIdiopathic osteonecrosis of the femoral head (ONFH) occurs at a relatively younger age. It is therefore important to prevent the resultant femoral head collapse and requirement of total hip arthroplasty in these patients. In 2003, we initiated concentrated autologous bone marrow aspirate transplantation (CABMAT), a joint-preserving treatment for ONFH, at our institution. Here, we report the long-term results of CABMAT treatment.MethodsWe retrospectively collated and analyzed the demographic and treatment data of 69 patients (109 hips) with idiopathic ONFH treated with CABMAT between April 2003 and April 2008.ResultsTotally, 44 patients (21 men, 23 women, 80 hips) completed the 10-year follow-up. The follow-up rate was 73.4%, and the mean follow-up period was 12.0 (range, 10.0–15.4) years. The mean age of the patients was 42.2 (range, 16.3–70.5) years. Using the Association Research Circulation Osseous (ARCO) classification system for preoperative analysis, 12, 31, 32, and 5 hips were classified as stages 1, 2, 3, and 4, respectively. The overall rate of conversion to total hip arthroplasty (THA) was 34% (27/80 hips). In a multivariate regression analysis, the preoperative stage of ONFH and the body mass index were found to correlate significantly with conversion to THA. Totally, 43 hips (of 80) were classified as belonging to the pre-collapse stage (i.e., stages 1 or 2). The overall collapse rate and the THA-conversion rate of these hips were estimated to be 49% (21/43) and 14% (6/43), respectively.ConclusionsOn the basis of our long-term findings, the minimally invasive and feasible CABMAT therapy can be utilized as one of a joint-preserving treatment for ONFH.

108. Posterior bone graft options and success in single-level circumferential lumbar fusions

BACKGROUND CONTEXT Achieving spinal fusion requires bone graft and is most reliable using an anterior/posterior technique. Anterior fusion, due to the large bony surface area between the vertebral bodies, results in reliable fusion. Instrumentation which provides stability, also increases the fusion rate. The bone graft for the posterior fusion may come from a variety of sources. Historically, bone graft was obtained from the iliac portion of the patient's own pelvis, IBG, but this may result in additional postoperative pain. Alternatives are currently the most common form of bone graft, but there is very little knowledge as to the superiority of one alternative over another. PURPOSE To determine the ability to achieve a solid posterior spinal fusion using sources of bone graft derived from IBG, bone morphogenic protein (BMP), or from donor bone combined with stem cells derived from either autologous bone marrow aspirate (BMA) or donor bone, fat, or amniotic membrane/fluid. STUDY DESIGN/SETTING Prospective randomized single-blinded clinical study of 6 comparative groups with 27 patients in each group. PATIENT SAMPLE Adults with advanced degenerative disc disease (DDD) who underwent single-level lumbar spinal fusion. OUTCOME MEASURES Outcomes included self-assessment of back and leg pain, pain drawing, ODI, pain medication usage, and procedure success. High resolution CT scans at one year postoperative assessed fusion rates between groups. Costs of graft materials were compared. METHODS Outcomes were obtained prospectively. Patients were enrolled over a 7-year period and followed for 2-4 years. All single-level circumferential fusions used BMP anteriorly, instrumentation, and patients were randomized into 6 groups with a different type of bone-graft used posteriorly. RESULTS CT scans found solid interbody fusion in 98% of patients. However, solid posterior fusions varied between groups: 98% IBG, 94% BMP, 78% concentrated BMA, 70% bone allograft stem cells, and 64% each for amniotic tissue and fat derived stem cells. Clinical improvement was significant from preop to 2-4 year follow-up within all groups (p CONCLUSIONS One-level circumferential spinal fusion using IBG was the most reliable and cost-effective graft material. BMP was highly effective and the most expensive. Concentrated autologous BMA had moderate fusion success and cost. Allograft products with varying cellularity were marginally effective for their high cost. FDA DEVICE/DRUG STATUS Unavailable from authors at time of publication.

Autologous bone marrow clot as an alternative to autograft for bone defect healing.

ObjectivesLong bone defects often require surgical intervention for functional restoration. The ‘gold standard’ treatment is autologous bone graft (ABG), usually from the patient’s iliac crest. However, autograft is plagued by complications including limited supply, donor site morbidity, and the need for an additional surgery. Thus, alternative therapies are being actively investigated. Autologous bone marrow (BM) is considered as a candidate due to the presence of both endogenous reparative cells and growth factors. We aimed to compare the therapeutic potentials of autologous bone marrow aspirate (BMA) and ABG, which has not previously been done.MethodsWe compared the efficacy of coagulated autologous BMA and ABG for the repair of ulnar defects in New Zealand White rabbits. Segmental defects (14 mm) were filled with autologous clotted BM or morcellized autograft, and healing was assessed four and 12 weeks postoperatively. Harvested ulnas were subjected to radiological, micro-CT, histological, and mechanical analyses.ResultsComparable results were obtained with autologous BMA clot and ABG, except for the quantification of new bone by micro-CT. Significantly more bone was found in the ABG-treated ulnar defects than in those treated with autologous BMA clot. This is possibly due to the remnants of necrotic autograft fragments that persisted within the healing defects at week 12 post-surgery.ConclusionAs similar treatment outcomes were achieved by the two strategies, the preferred treatment would be one that is associated with a lower risk of complications. Hence, these results demonstrate that coagulated BMA can be considered as an alternative autogenous therapy for long bone healing.Cite this article: Z. X. H. Lim, B. Rai, T. C. Tan, A. K. Ramruttun, J. H. Hui, V. Nurcombe, S. H. Teoh, S. M. Cool. Autologous bone marrow clot as an alternative to autograft for bone defect healing. Bone Joint Res 2019;8:107–117. DOI: 10.1302/2046-3758.83.BJR-2018-0096.R1.

Tracking Cell Transplants in Femoral Osteonecrosis with Magnetic Resonance Imaging: A Proof-of-Concept Study in Patients.

Osteonecrosis is a devastating complication of high-dose corticosteroid therapy in patients with cancer. Core decompression for prevention of bone collapse has been recently combined with the delivery of autologous concentrated bone marrow aspirates. The purpose of our study was to develop an imaging test for the detection of transplanted bone marrow cells in osteonecrosis lesions. In a prospective proof-of-concept clinical trial (NCT02893293), we performed serial MRI studies of nine hip joints of 7 patients with osteonecrosis before and after core decompression. Twenty-four to 48 hours prior to the surgery, we injected ferumoxytol nanoparticles intravenously to label cells in normal bone marrow with iron oxides. During the surgery, iron-labeled bone marrow cells were aspirated from the iliac crest, concentrated, and then injected into the decompression track. Following surgery, patients received follow-up MRI up to 6 months after bone marrow cell transplantation. Iron-labeled cells could be detected in the access canal by a dark (negative) signal on T2-weighted MR images. T2* relaxation times of iron-labeled cell transplants were significantly lower compared with unlabeled cell transplants of control patients who were not injected with ferumoxytol (P = 0.02). Clinical outcomes of patients who received ferumoxytol-labeled or unlabeled cell transplants were not significantly different (P = 1), suggesting that the added ferumoxytol administration did not negatively affect bone repair. This immediately clinically applicable imaging test could become a powerful new tool to monitor the effect of therapeutic cells on bone repair outcomes after corticosteroid-induced osteonecrosis.

Percutaneous piercing cortical bone at fracture ends and local injection of autologous concentrated bone marrow aspirate and platelet rich plasma for treatment of delayed fracture union

Objective To evaluate the clinical efficacy of percutaneous piercing cortical bone at fracture ends and local injection of autologous concentrated bone marrow aspirate (cBMA) and platelet rich plasma (PRP) in the treatment of delayed fracture union. Methods A retrospective study was performed on the clinical data of 34 patients with delayed fracture union who had been treated at Department of Orthopaedics, Luoyang Zhenggu Hospital of Henan Province from April 2014 to February 2017. They were 26 males 8 females, aged from 18 to 63 years (average, 36.7 years). There were 15 femoral, 11 tibial, 5 humerus and 3 ulnar fractures. According to the Weber-Crech classification, 14 cases belonged to the type of rich blood supply-active end hypertrophy and 20 to the type of poor blood supply and malnutrition. There were 28 closed and 6 open fractures. Of this cohort, 21 cases had their primary fixation, 7 had revision once, 4 had revision twice, and 2 had revision more than thrice; 19 cases had intramedullary fixation, 12 had plate fixation and 3 had external fixation. Autologous iliac bone grafting was performed previously in 19 cases. Kirschner wire was used under fluoroscopy to pierce percutaneously the cortical bone at fracture ends; bone marrow blood and peripheral venous blood were collected to prepare autologous cBMA and PRP which were to be injected locally at the fracture ends after mixture. At the last follow-up, the patients were evaluated by visual analogue scale (VAS), SF-36 health survey summary scores and modified Radiographic Union Score for Tibia (RUST). Results The patients were followed up for 12 to 42 months (average, 21.5 months). Thirty-one patients healed after surgery, yielding a healing rate of 91.2%. The healing time averaged 5.3 months (from 4 to 10 months). No patient reported such complications as infection or neurovascular injury. At the last follow-up, the VAS scores of the 34 patients were 1.3±0.6 points, significantly lower than the preoperative 5.4±3.6 points (P<0.05); the postoperative SF-36 scores 74.8±16.5 points, significantly increased than the preoperative 44.8±15.6 scores (P<0.05); the RUST scores 3.3±0.4 points, significantly higher than the preoperative 1.6±0.8 points (P<0.05). Conclusions Minimally invasive percutaneous piercing of K-wire on the cortical bone at the fracture ends may result in fluid leakage and restart bone healing process. At the same time, local injection of autologous cBMA and PRP may increase the number and concentration of local bone marrow mesenchymal stem cells and growth factors, promoting fracture healing. Key words: Fractures, bone; Bone marrow; Platelet-rich plasma; Surgical procedures, minimally invasive; Delayed healing

How stem cell composition in bone marrow aspirate relates to clinical outcomes when used for cervical spine fusion.

Anterior cervical discectomy and fusion (ACDF) is performed to relieve pain caused by degenerative disk disease and nerve obstruction. As an alternative to bone graft, autologous concentrated bone marrow aspirate (CBMA) is used to achieve vertebral fusion with a satisfactory success rate. This has been attributed in part to bone marrow-resident mesenchymal stromal cells (MSCs) with the capacity to differentiate into osteoblasts and generate bone tissue. To date, there has been no study comparing cellular yields, MSC frequencies and their osteogenic potential with ACDF outcome. Patients (n = 24) received ACDF with CBMA and allograft bone matrix. Colony forming unit fibroblast (CFU-F) and CFU-osteoblasts (CFU-O) assays were performed on CBMA samples to enumerate MSCs (CFU-F) and osteogenic MSCs (CFU-O). CFUs were normalized to CBMA volume to define yield and also to mononuclear cells (MNC) to define frequency. After 1-year, fusion rates were good (86.7%) with pain and disability improved. There was a negative relationship between MNC and CFU-F measurements with age of patient and CFU-Os negatively correlated with age in females but not males. Tobacco use did not affect CBMA but was associated with poorer clinical outcome. Surprisingly, we found that while high-grade fusion was not associated with CFU-O, it correlated strongly (p<0.0067) with CBMA containing the lowest frequencies of CFU-F (3.0x10-6–5.83x10-5 CFU-F/MNC). MNC levels alone were not responsible for the results. These observations suggest that osteogenesis by human bone marrow is controlled by homeostatic ratio of MSCs to other cellular bone marrow components rather than absolute level of osteogenic MSCs, and that a lower ratio of MSCs to other cellular components in marrow tends to predict effective osteogenesis during ACDF. The results presented herein challenge the current dogma surrounding the proposed mechanism of MSCs in bone healing.

Increased Internal Porosity and Surface Area of Hydroxyapatite Accelerates Healing and Compensates for Low Bone Marrow Mesenchymal Stem Cell Concentrations in Critically-Sized Bone Defects

For clinical treatment of skeletal defects, osteoinductive scaffolds must have the ability to conform to the unique geometry of the injury site without sacrificing biologically favorable properties, including porosity. This investigation seeks to combine the osteoinductive properties of porous hydroxyapatite (HA) scaffolds with the beneficial handling characteristics of granules or putties, while evaluating the effects of mesenchymal stem cell (MSC) concentration on the composite grafts’ ability to regenerate bone in vivo. The results demonstrate that porous HA granules regenerate significantly larger volumes of bone compared to non-porous HA. Increased MSC concentrations in autologous bone marrow aspirate (BMA) contributed to greater bone regeneration. This effect was most predominant with non-porous HA. While the extent of bone regeneration using non-porous HA was strongly correlated with MSC concentration of the marrow, porous HA microparticles combined with autologous BMA were successful in faster treatment of critically-sized bone defects and with less dependence on the MSC concentration than non-porous HA.

Wednesday, September 26, 2018 7:35 AM–9:00 AM ePosters

BACKGROUND CONTEXT The need for improved fusion technology led to the development of a lumbar interbody fusion implant with unique biomechanical characteristics that has the potential to enhance bone on-growth and through-growth. The proprietary implant using truss-based technology allows loading along the trusses throughout the fusion volume of the device which may promote stem cell differentiation into osteoblast and speed up the fusion process. PURPOSE It is hypothesized that fusions performed using the truss-based technology will result in higher fusion rates and reduced times for bone formation due to the biomechanical properties of the implant design when compared to annular implant designs. The purpose of this study was to evaluate the performance of the truss-based technology with two different graft materials, crushed cancellous allograft bone or autologous bone marrow aspirate. STUDY DESIGN/SETTING Prospective, randomized clinical trial performed in a university setting. PATIENT SAMPLE Between January 2015 and February 2016, 42 consecutive patients were recruited, consented and randomized into one of two previously defined study groups and underwent the index study procedure. There was one patient in Group 2 that withdrew from the study prior to surgery. In addition, there were 2 patient deaths due to cardiac events (one in each group) determined to be unrelated to the surgical procedure. OUTCOME MEASURES The clinical outcome measures included the Oswestry Disability Index (ODI), Visual/Analog Scales (VAS) separately assessing back and leg pain, EQ5-D and adverse events. METHODS Patients were randomized into one of two treatment groups (Group 1: crushed cancellous allograft bone vs. Group 2: autologous bone marrow aspirate [BMA] both receiving one- or two-level lumbar interbody fusion with supplemental fixation. It was determined that a total of 40 patients (20 patients per group) were needed to achieve a statistical significance level of 0.05. The 4WEB Anterior Spine Truss System Interbody Fusion Device (ASTS; 4WEB Medical, Frisco, TX, USA) was used in all cases. Clinical and radiographic data was obtained prior to hospital discharge and at 3, 6 and 12-months postoperatively. All radiographs were independently reviewed. RESULTS Except for changes from the preoperative assessment for total EQ-5D (p CONCLUSIONS The clinical and radiographic results from this prospective, randomized study have shown that reliable clinical and radiographic evidence of fusion can be obtained utilizing a truss-based web technology implant independent of the use of either crushed cancellous homologous bone chips or BMA alone. As a result of these findings, there may be intraoperative biologic cost reduction implications across multiple patient populations.

The Effect of Combined Therapy, Percutaneous Concentrated Autologous Bone Marrow Transplantation, and Low-Intensity Pulsed Ultrasound (LIPUS) in Treatment of Femoral Head Osteonecrosis

Objective: We describe a novel, combined approach to the treatment of osteonecrosis of the femoral head (ONFH) based on concentrated autologous bone marrow aspirates (CABMAT) and low-intensity pulsed ultrasound (LIPUS). Patients and Methods: The 7 male and 7 female patients (mean age: 40 years; 22 hips) underwent CABMAT followed by 6 months of continuous LIPUS. The mean follow-up period was 26 months. All patients were assessed using the visual analogue scale (VAS) for pain and the Japanese Orthopedic Association (JOA) hip score. Clinical and plain radiographic evaluations were performed before transplantation and at the most recent follow-up. Computed tomography (CT) scans were obtained before and 12 months after grafting. Results: The VAS and JOA scores improved in all patients. Collapse progressed in 8 of the 22 hips, but none required total hip arthroplasty. The mean volume of new bone formation 12 months' post-transplantation as seen on CT was 1256 mm3. New bone formation was observed in all patients. Discussion: The multiple benefits of LIPUS include improved local blood flow, accelerated production of angiogenesis-inducing cytokines, accelerated differentiation of mesenchymal stem cells to form osteoblasts, and the inhibition of osteoclast production and differentiation. This combined therapy is noninvasive, feasible, and joint-preserving in most ONFH patients.

Mid-term results of concentrated autologous bone marrow aspiratetransplantation for corticosteroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus.

We had previously established concentrated autologous bone marrow aspirate transplantation (CABMAT), a one-step, low-invasive, joint-preserving surgical technique for treating osteonecrosis of the femoral head (ONFH). This study aimed to evaluate the effects of CABMAT as a hip-preserving surgical approach, preventing conversion to total hip arthroplasty (THA) and femoral head collapse in patients with systemic lupus erythematosus (SLE). Since 2003, 52 SLE patients (8 male, 44 female, 92 hips, mean age 35.3 (16-77) (years) were treated with CABMAT. The mean follow-up period was 5.5 (0.7-14) years. Conversion rate to THA and its predicting factors were analyzed. The overall conversion rate to THA was 29% (27/92). Conversion rate to THA was 0% (0/3), 0% (0/4), 22% (9/41), and 41% (18/44) in types A, B, C1, and C2, respectively. Conversion rate to THA was 26% (5/19), 26% (6/23), 28% (11/39), 44% (4/9), and 50% (1/2) in stages 1, 2, 3A, 3B, and 4, respectively. In multivariate logistic regression analysis, sex, body mass index (BMI), pre-operative type, and pre-operative stage were significantly correlated with conversion to THA. The conversion rate to THA was lower than that in the natural course and core decompression, but was higher than that seen in other bone marrow transplantation and osteotomy. Since sex, pre-operative type, and pre-operative stage were significantly correlated with conversion to THA, it is suggested that the higher proportion of women, advanced stage (stage 3A or above), and advanced type (type C or above) in this study affected the THA conversion rate.

Articulate Cartilage Enriched With Autologous Bone Marrow Aspirate as an Approach of Pain Amelioration and Functionality Restoration in Osteoarthritis Patients Older Than 50 Years-Old

Articulate Cartilage Enriched With Autologous Bone Marrow Aspirate as an Approach of Pain Amelioration and Functionality Restoration in Osteoarthritis Patients Older Than 50 Years-Old

Comparison of Juvenile Allogenous Articular Cartilage and Bone Marrow Aspirate Concentrate Versus Microfracture With and Without Bone Marrow Aspirate Concentrate in Arthroscopic Treatment of Talar Osteochondral Lesions.

The purpose of this study was to compare the functional and radiographic outcomes of patients who received juvenile allogenic chondrocyte implantation with autologous bone marrow aspirate (JACI-BMAC) for treatment of talar osteochondral lesions with those of patients who underwent microfracture (MF). A total of 30 patients who underwent MF and 20 who received DeNovo NT for JACI-BMAC treatment between 2006 and 2014 were included. Additionally, 17 MF patients received supplemental BMAC treatment. Retrospective chart review was performed and functional outcomes were assessed pre- and postoperatively using the Foot and Ankle Outcome Score and Visual Analog pain scale. Postoperative magnetic resonance images were reviewed and evaluated using a modified Magnetic Resonance Observation of Cartilage Tissue (MOCART) score. Average follow-up for functional outcomes was 30.9 months (range, 12-79 months). Radiographically, average follow-up was 28.1 months (range, 12-97 months). Both the MF and JACI-BMAC showed significant pre- to postoperative improvements in all Foot and Ankle Outcome Score subscales. Visual Analog Scale scores also showed improvement in both groups, but only reached a level of statistical significance ( P < .05) in the MF group. There were no significant differences in patient reported outcomes between groups. Average osteochondral lesion diameter was significantly larger in JACI-BMAC patients compared to MF patients, but size difference had no significant impact on outcomes. Both groups produced reparative tissue that exhibited a fibrocartilage composition. The JACI-BMAC group had more patients with hypertrophy exhibited on magnetic resonance imaging (MRI) than the MF group ( P = .009). JACI-BMAC and MF resulted in improved functional outcomes. However, while the majority of patients improved, functional outcomes and quality of repair tissue were still not normal. Based on our results, lesions repaired with DeNovo NT allograft still appeared fibrocartilaginous on MRI and did not result in significant functional gains as compared to MF. Level III, comparative series.