Positive early clinical outcomes of bone marrow aspirate concentrate for osteoarthritis using a novel fenestrated trocar.

BACKGROUND: This study sought to assess early clinical outcomes for knee osteoarthritis (OA) patients undergoing bone marrow aspirate concentrate (BMAC) treatment using a novel closed-end, fenestrated trocar (FT) that does not require centrifugation. METHODS: A prospective cohort of 17 knee OA patients undergoing BMAC treatment with the FT system from March 2018 to March 2019 was retrospectively evaluated. Approximately 10 mL of BMAC was harvested, no centrifugation was performed, and the BMAC was injected into the affected knee. Clinical outcomes were assessed at baseline, six weeks, and 12 weeks. This study has no affiliation with/vested-interest in the FT system. RESULTS: There were significant improvements in nearly all outcomes from baseline to 12 weeks. Specific improvements included Knee Injury and OA Outcome Score (KOOS) activities-of-daily-living (61.1 ± 9.2 [mean ± 95% confidence interval] to 89.3 ± 6, p = 0.001), quality-of-life (32.7 ± 9.3 to 66.1 ± 17.9, p = 0.003), sports/recreation (36.9 ± 10.6 to 72.6 ± 26.3, p = 0.006), and pain (53.8 ± 9.3 to 83 ± 10.2, p = 0.001); Lysholm scores (55.5 ± 8.4 to 77.3 ± 10.5, p = 0.009); and visual analog pain scores (5.68 ± 1.14 to 2.07 ± 1.86, p = 0.003). Individually, at least 75% of patients exhibited improvement in all KOOS categories at six weeks and at least 85% at 12 weeks. CONCLUSIONS: BMAC treatment with an FT system that does not require centrifugation resulted in significant improvements in early pain and function scores for knee OA. The symptomatic improvements in this study were similar to or greater than what has been reported using traditional needles. These data may provide clinicians with comfort in using an FT system and provide motivation for future randomized-controlled trials comparing aspiration techniques.

Isolation, Differentiation, and Characterization of Human Bone Marrow Stem Cells In Vitro and In Vivo.

In this chapter, we describe techniques for the isolation and characterisation of skeletal stem cells from human bone marrow. The methods for enrichment of STRO-1+ and STRO-4+ cells using magnetic activated cell sorting are described and we also detail techniques for establishing and characterizing osteogenic, adipogenic, and chondrogenic cultures from these cells. Finally, we present methods for studying the ability of these cells to produce bone in vivo using diffusion chambers which have been implanted subcutaneously into mice.

A Review of Commercially Available Point-of-Care Devices to Concentrate Bone Marrow for the Treatment of Osteoarthritis and Focal Cartilage Lesions.

OBJECTIVE: Mesenchymal stem cells (MSCs) are a promising cell-based therapy treatment option for several orthopedic indications. Because culture expansion of MSC is time and cost intensive, a bedside concentration of bone marrow (BM) aspirate is used as an alternative. Many commercial systems are available but the available literature and knowledge regarding these systems is limited. We compared different point-of-care devices that concentrate BM (BMC) by focusing on technical features and quality parameters to help surgeons make informed decisions while selecting the appropriate device. METHODS: We compared published data on the BMC devices of Arteriocyte, Arthrex, Celling Biosciences, EmCyte, Exactech, ISTO Tech, Harvest Tech/Terumo BCT, and Zimmer/BIOMET regarding technical features (centrifugation speed/time, input/output volume, kit components, type of aspiration syringes, filter usage) and quality parameters of their final BMC product (hematocrit, concentration of platelets and total nucleated cells, concentration of MSC and connective tissue progenitor cells). RESULTS: The systems differ significantly in their technical features and centrifugation parameters. Only the fully automated systems use universal kits, which allow processing different volumes of BM. Only the Arthrex system allows selection of final hematocrit. There was no standardized reporting method to describe biologic potency. CONCLUSIONS: Based on the data obtained in this review, recommending a single device is not possible because the reported data could not be compared between devices. A standardized reporting method is needed for valid comparisons. Furthermore, clinical outcomes are required to establish the true efficacy of these systems. We are conducting additional studies for more careful comparison among the devices.

Percutaneous Ultrasound-Guided Musculoskeletal Applications of Autologous Bone Marrow Aspirate Concentrate: Preliminary Experience From a Single Institution.

Emerging musculoskeletal applications for local administration of autologous bone marrow aspirate concentrate (BMAC) include treatment of fractures, osteonecrosis, osteochondral injuries, osteoarthritis, ligament injury, tendon injury, and tendonopathies. Ultrasound-guided technique for various BMAC injection sites is detailed in this technical report and our preliminary clinical experience outlined.Five patients, 1 woman and 4 men, were treated with 6 peri/intratendinous (n = 4) or intraarticular (n = 2) BMAC injections between July 5, 2015 and December 31, 2016 for the clinical indications of common hamstrings origin tendinosis (n = 4), hip labral tear (n = 1), and osteochondral lesion of the talus (n = 1).All procedures were technically successful, with BMAC locally administered to the therapeutic target and no procedural complications observed. Clinical follow-up was available for 5 of 6 procedures. Four of 5 injections resulted in self-reported symptomatic improvement (clinical follow-up range, 2-12 months). One 72-year-old man with right common hamstrings origin tendinosis reported no improvement after BMAC injection.The technology is now available to support ultrasound-guided, autologous BMAC administration by the musculoskeletal interventionalist for common indications. Our initial clinical experience is consistent with early reports in the literature. This technique is well tolerated by symptomatic patients on an outpatient basis, and rates of self-reported symptomatic relief are high. Mechanism of action, long-term safety, and long-term clinical efficacy remain largely undefined.

Combined Therapy with Shock Wave and Retrograde Bone Marrow-Derived Cell Transplantation for Osteochondral Lesions of the Talus.

Multiple treatment strategies have been developed for osteochondral lesions (OCLs) of the talus. The purpose of this retrospective study was to assess retrograde autologous bone marrow cell (BMC) transplantation via core drilling (CD) combined with focused extracorporeal shock wave treatment (ESWT) in undisplaced OCL of the talus. A total of 69 patients with unilateral osteochondral lesions of the talus (Hepple grade I-III) were divided into two groups: 41 patients received combined therapy of ESWT and BMC transplantation (group A), while 28 were administered BMC transplantation alone (group B). The patients were followed up clinically and radiographically for a minimum of 2 years. Mean follow-up was 4.1 ± 2.8 years. AOFAS scores increased more significantly while pain intensity levels decreased in group A after treatment, compared with group B values (P < 0.001). In MRI follow-up, a more remarkable improvement of OCLs of the talus was observed in group A compared with group B (P = 0.040). Therefore, the combined technique reported here is a highly effective therapeutic option in OCLs of the talus with intact cartilage. It promotes patient recovery with pain control, and improves clinical outcome for more than 2 years after surgery.

bFGF binding cardiac extracellular matrix promotes the repair potential of bone marrow mesenchymal stem cells in a rabbit model for acute myocardial infarction.

To assess the effect of basic fibroblast growth factor-binding extracellular matrix (bFGF-ECM) combined with bone marrow mesenchymal stem cells (BMSCs) transplantation on acute myocardial infarction (AMI) and explore the underlying mechenisms. Rabbit hearts were processed by decellularization with sodium dodecyl sulfate (SDS) perfusion, heparin immobilization, bFGF-binding and homogenization, for preparation of bFGF-binding cardiac ECM suspension (bFGF-ECM). Thereafter, the characteristics of bFGF release were analyzed in vitro. Following ligation of the mid-third of the left anterior descending artery, the rabbits were divided into a control group (no treatment), BMSCs group (BMSCs transplantation), bFGF-ECM group (bFGF-ECM implantation), and BMSCs + bFGF-ECM group (BMSCs and bFGF-ECM implantation). Apoptosis and differentiation of implanted BMSCs, and the left ventricular (LV) remodeling and function were assessed. The ex vivo proliferation, apoptosis, migration and differentiation of BMSCs were determined after exposure to bFGF and/or ECM. The ECM could sustainably release bFGF. 24 h and 6 weeks after the operation, improved viability and differentiation of the implanted BMSCs, as well as inhibited dilatation and preserved function of the left ventricle (LV), were significant in the BMSCs + bFGF-ECM group compared with other groups (P < 0.05), although BMSCs and ECM-bFGF groups also showed better results than control group (P < 0.05). Additionally, ECM and bFGF showed a synergistic effect on BMSCs proliferation, viability, migration and differentiation. The combination of bFGF-binding ECM and BMSCs implantation may promote myocardial regeneration and LV function, and become a new strategy for the treatment of AMI.

Comparison of free fibular flaps with reamer-irrigator-aspirator bone grafts for the reconstruction of critical-sized mandibular defects.

OBJECTIVE: Vascularized bone flaps are currently indicated for reconstructing mandibular defects 6 cm or larger. This technique can result in donor-site morbidity and requires microsurgery. To explore alternative methods of mandibular reconstruction, we sought to compare bone graft obtained with the reamer-irrigator-aspirator (RIA) device with the free fibula (FF) flap for the reconstruction of a critical-sized mandibular defect. METHODS: Sixteen 3-month-old Yorkshire pigs underwent 6-cm full-thickness resection of the left mandible. For the FF group (n = 8), an osseous FF flap was raised from the left leg and placed into the defect. For the RIA group (n = 8), a RIA Instrument Set was used on the ipsilateral femur to ream the femoral canal and harvest RIA putty. This putty containing medullary bone marrow contents and cortical bone was packed into the defect. At the study end point, volumetric, biomechanical, and histologic analyses were performed. RESULTS: Operative times were significantly shorter in the RIA group (RIA,126 [30] min; FF, 346 [50] min; P < 0.05). Biomechanical testing of reconstructed sites showed no significant difference in maximum fracture loads between both groups (RIA, 468 [97] N; FF, 689 [262] N; P = 0.11). Mean (SD) volume ratio of bone growth at the reconstructed sites was comparable between both groups (RIA, 71% [4.5%]; FF, 72% [3.3%]; P = 0.60). Equal bone quality was confirmed histologically. CONCLUSIONS: The RIA technique significantly reduces operative time and provides bone of equal strength and histologic quality to FF flap reconstruction in a large animal model. The RIA method may represent an efficient technique for the reconstruction of craniomaxillofacial defects.

A prospective comparison of 3 approved systems for autologous bone marrow concentration demonstrated nonequivalency in progenitor cell number and concentration.

OBJECTIVES: To evaluate the efficacy of 3 commercially available systems: the Harvest SmartPReP 2 BMAC, Biomet BioCUE, and Arteriocyte Magellan systems. We compared the number and concentration of progenitor cells achieved both before and after centrifugation and the percentage of progenitor cells salvaged after centrifugation. METHODS: Forty patients, mean age 47 ± 18 years (range: 18-92 years, 19 male/21 female) were prospectively consented for bilateral iliac crest aspiration. The first 20 aspirations compared the Harvest and Biomet systems, and based on those results, the second 20 compared the Harvest and Arteriocyte systems. One system was randomly assigned to each iliac crest. Each system's unique marrow acquisition process and centrifugation mechanism was followed. Samples for analysis were taken both immediately before the marrow was put into the centrifugation system (after acquisition), and after centrifugation. The number of progenitor cells in each sample was estimated by counting the connective tissue progenitors (CTPs). RESULTS: The Harvest system achieved a significantly greater number and concentration of CTPs both before and after centrifugation when compared to the Biomet system. There was no difference in the percent yield of CTPs after centrifugation. There was no significant difference in the number and concentration of CTPs between the Harvest and Arteriocyte systems before centrifugation, but the Harvest system had a significantly greater number and concentration of CTPs after centrifugation. The Harvest system also had a significantly higher percent yield of CTPs after centrifugation compared with the Arteriocyte system. CONCLUSIONS: The Harvest system resulted in a greater CTP number and concentration after centrifugation when compared with the Biomet and Arteriocyte systems and may thus provide increased osteogenic and chondrogenic capacity.

Comparing peripheral blood stem cell collection using the COBE Spectra, Haemonetics MCS+, and Baxter Amicus.

Peripheral blood stem cells (PBSC) have become the most common source of hematopoietic cells for allogeneic or autologous blood and marrow transplantation (BMT). We performed an evaluation of PBSC collections using three different apheresis systems in two major transplantation centers in Singapore. Patients undergoing autologous BMT and donors collecting for allogeneic BMT were harvested using the COBE Spectra, Haemonetics MCS+, or Baxter Amicus. There were 99 Spectra collections (61 were autologous), 81 MCS+ collections (35 were autologous) and 38 Amicus collections (33 were autologous). Our data shows that the Amicus not only processed larger peripheral blood volumes but also yielded larger PBSC volume (P-value<0.05). In terms of PBSC products, the Spectra produced more WBC, WBC/liter blood processed, and WBC/kg (P-value<0.05). The Spectra and MCS+ produced comparable amount of CD34+ cells. Amicus collected 50% less platelets compared to Spectra and MCS+. The total CD34+ cells in the PBSC products was linearly correlated to the circulating CD34+ cells using Spectra, MCS+, and Amicus. Our results suggest that, compared to MCS+ and Amicus, collecting PBSC using the COBE Spectra can produce more WBC with a similar number of CD34+ cells. With a linear correlation of circulating CD34+ cells to the total CD34+ cells in the products, the availability of an automated procedure, no rotating seal, and a small extracorporeal volume, the Spectra appears to be the preferred machine for PBSC collection.

Treatment of severe post-traumatic bone defects with autologous stem cells loaded on allogeneic scaffolds.

Mesenchymal stem cells may differentiate into angiogenic and osteoprogenitor cells. The effectiveness of autologous pluripotent mesenchymal cells for treating bone defects has not been investigated in humans. We present a case series to evaluate the rationale of using nucleated cells from autologous bone marrow aspirates in the treatment of severe bone defects that failed to respond to traditional treatments. Ten adult patients (mean age, 49.6-years-old) with severe bone defects were included in this study. Lower limb bone defects were >or=5 cm3 in size, and upper limb defects .or=2 cm3. Before surgery, patients were tested for antibodies to common pathogens. Treatment consisted of bone allogeneic scaffold enriched with bone marrow nucleated cells harvested from the iliac crest and concentrated using an FDA-approved device. Postsurgery clinical and radiographic follow-up was performed at 1, 3, 6, and 12 months. To assess viability, morphology, and immunophenotype, bone marrow nucleated cells were cultured in vitro, tested for sterility, and assayed for the possible replication of adventitious (contaminating) viruses. In 9 of 10 patients, both clinical and radiographic healing of the bone defect along with bone graft integration were observed (mean time, 5.6 months); one patient failed to respond. No post-operative complications were observed. Bone marrow nucleated cells were enriched 4.49-fold by a single concentration step, and these enriched cells were free of microbial contamination. The immunophenotype of adherent cells was compatible with that of mesenchymal stem cells. We detected the replication of Epstein-Barr virus in 2/10 bone marrow cell cultures tested. Hepatitis B virus, cytomegalovirus, parvovirus B19, and endogenous retrovirus HERV-K replication were not detected. Overall, 470 to 1,150 million nucleated cells were grafted into each patient. This case series, with a mean follow-up of almost 2 years, demonstrates that an allogeneic bone scaffold enriched with concentrated autologous bone marrow cells obtained from the iliac crest provides orthopedic surgeons a novel option for treating important bone defects that are unresponsive to traditional therapies.

Transendocardial autologous bone marrow in myocardial infarction induced heart failure, two-year follow-up in an open-label phase I safety study (the TABMMI study).

AIMS: To assess the hypothesis that fluoroscopically-guided helical needle transendocardial delivery of autologous bone marrow (ABM) mononuclear cells (MNCs) in chronic post myocardial infarction patients is safe and improves ejection fraction (EF). METHODS AND RESULTS: Twenty ischaemic heart failure patients with an EF ≤40% were enrolled. ABMMNCs were prepared, counted for CD34+ and CD133+ content, and delivered percutaneously to the heart at 5 to 10 peri-infarct sites. Two-dimensional (2D) transthoracic echocardiography, EF measurements, Holter, and exercise tolerance time (ETT) were performed at baseline, one week (wk), and 6, 12, and 24 months (mo). 96±29 million ABMMNCs were injected into 8.5±2.6 peri-infarct sites over 42±17 minutes (n=20). There were no adverse events associated with the catheter-based cell transplantation procedure or significant increases in ventricular events on Holter. EF improved over baseline from 34.9±4.3% to 41.9±5.1% at 12 mo to 42.2±7.1% (p=0.00005) at 24 mo. ETT improvements were statistically significant from 246±113 sec to 373±183 sec at 12 mo and 371±181 sec at 24 mo (p=0.006). CONCLUSIONS: ABMMNCs delivered with the helical needle transendocardial catheter was safe in this uncontrolled open label study. Increased EF and ETT support the safety of the procedure and technologies involved and warrant additional investigation.

The subchondral bone in articular cartilage repair: current problems in the surgical management.

As the understanding of interactions between articular cartilage and subchondral bone continues to evolve, increased attention is being directed at treatment options for the entire osteochondral unit, rather than focusing on the articular surface only. It is becoming apparent that without support from an intact subchondral bed, any treatment of the surface chondral lesion is likely to fail. This article reviews issues affecting the entire osteochondral unit, such as subchondral changes after marrow-stimulation techniques and meniscectomy or large osteochondral defects created by prosthetic resurfacing techniques. Also discussed are surgical techniques designed to address these issues, including the use of osteochondral allografts, autologous bone grafting, next generation cell-based implants, as well as strategies after failed subchondral repair and problems specific to the ankle joint. Lastly, since this area remains in constant evolution, the requirements for prospective studies needed to evaluate these emerging technologies will be reviewed.

Intraoperative adjunctive stem cell treatment in patients with critical limb ischemia using a novel point-of-care device.

INTRODUCTION: In a prospective trial we tested whether adjunctive intraoperative stem cell treatment in patients with critical limb ischemia (CLI) can be performed safely in combination with bypass surgery and/or interventional treatment. The end point of our study was the safety and integrity of a novel point-of-care system used in patients with CLI. METHODS: We included only patients with CLI and tissue loss according to Rutherford categories 4-6. The Harvest Bone Marrow Aspirate Concentrate System consists of an automated, microprocessor-controlled dedicated centrifuge with decanting capability and the accessory BMAC Pack for processing a patient's bone marrow aspirate (BMA). The centrifuge is portable and enables BMA to be rapidly processed in the operating room to provide an autologous concentrate of nucleated cells for immediate injection. The surgeon aspirated 120 ml BMA from the iliac crest. RESULTS: Eight consecutive patients were treated according to the study protocol. The mean follow-up period was 9.2 months (range 2-18). Stem cells were always injected during the final revascularization attempt. One minor amputation and two major amputations were required. In five of eight patients there was a discrete increase in the ankle-brachial index post-stem cell treatment. The dose of stem cells after centrifugation was 17.2 (range 13.8-54.2)x10E6 CD34-positive cells and 7.8 (range 1.8-35.9)x10E6 CD133-positive cells. The injected dose of VEGFR-2-coexpressing stem cells was 0.5-5.7x10E4. CONCLUSION: We were able to show that the buffy coat preparation using a point-of-care system is a simple and fast method to enrich stem cells from BMAs. This automated system gives high recovery rates and good reproducibility.

Natural bone collagen scaffold combined with autologous enriched bone marrow cells for induction of osteogenesis in an ovine spinal fusion model.

Autologous bone graft, the standard of bone grafting in achieving spinal fusion, is associated with several limitations and complications. The use of bone marrow cells (BMCs) as a potential cell source for spinal fusion, combined with a suitable scaffold to promote bone formation, may be a better choice. The aims of this study were to evaluate the efficacy of natural bone collagen scaffold (NBCS) combined with autologous-enriched BMCs for induction of osteogenesis in vitro and in vivo. Ovine-enriched BMCs were co-cultured with NBCS for 1, 2, 3, and 4 weeks to investigate whether NBCS would support the population expansion and differentiation of enriched BMCs. Using an ovine interbody fusion model, NBCS seeded with autologous enriched BMCs was implanted into the lumbar disc space. Fusion outcomes were compared with the use of the autograft, NBCS without BMCs, and BMCs without NBCS. In vitro results demonstrated that NBCS facilitated the population expansion and differentiation of ovine-enriched BMCs, promoting the expression of collagen type I and the formation of a mineralized matrix. The use of NBCS combined with enriched BMCs in vivo enhanced the spinal fusion rate (6 of 6 at 10 week) (p < 0.05), the biomechanical stiffness of fusion masses, and bone volume at the fusion site (p < 0.05). Histological findings also revealed that a combination of NBCS and BMCs induced new bone formation that integrated well with host bone tissue. In conclusion, NBCS is an effective scaffold that supports ovine-enriched BMCs. The combination of NBCS and BMCs may be a useful alternative for autograft in induction of spinal fusion.

Autologous bone marrow graft and treatment of delayed and non-unions of long bones: technical aspects.

This article reports the technique of percutaneous autologous bone marrow injection as a minimally invasive method alternative to open grafting techniques in the treatment of delayed unions and non-unions. Despite continuous advances in the treatment of long bone fractures, disturbances of healing processes remain a difficult challenge for orthopaedic surgeons. Percutaneous administration of substances with osteoinductive and osteogenic properties offers the advantage of decreased morbidity associated with the classic open grafting techniques. This makes it worth exploring before embarking on more extensive open surgery. The authors present the main technical stages of the percutaneous bone marrow grafting (bone marrow aspiration, concentration, intra-osseous re-injection and post-operative protocol) with a short literature review about this topic.

Overlap between in vitro donor antihost and in vivo posttransplantation TCR Vbeta use: a new paradigm for designer allogeneic blood and marrow transplantation.

Following allogeneic blood and marrow transplantation (BMT), mature donor T cells can enhance engraftment, counteract opportunistic infections, and mount graft-versus-tumor (GVT) responses, but at the risk of developing graft-versus-host disease (GVHD). With the aim of separating the beneficial effects of donor T cells from GVHD, one approach would be to selectively deplete subsets of alloreactive T cells in the hematopoietic cell inoculum. In this regard, TCR Vbeta repertoire analysis by CDR3-size spectratyping can be a powerful tool for the characterization of alloreactive T-cell responses. We investigated the potential of this spectratype approach by comparing the donor T-cell alloresponses generated in vitro against patient peripheral blood lymphocytes (PBLs) with those detected in vivo posttransplantation. The results indicated that for most Vbeta families that exhibited alloreactive CDR3-size skewing, there was a robust overlap between the in vitro antipatient and in vivo spectratype histograms. Thus, in vitro spectratype analysis may be useful for determining the alloreactive T-cell response involved in GVHD development and, thereby, could serve to guide select Vbeta family depletion for designer transplants to improve outcomes.

Sonographically guided venous puncture and fluoroscopically guided placement of tunneled, large-bore central venous catheters for bone marrow transplantation-high success rates and low complication rates.

BACKGROUND AND OBJECTIVE: Traditionally, large lumen, tunneled central venous catheters have been implanted by surgeons. We used a technique of sonographically guided jugular venous puncture and fluoroscopically guided catheter placement to achieve a high rate of technical success and to reduce complication rates. MATERIALS AND METHODS: Between June 2002 and December 2006, 186 Patients have been referred to the Radiology Department for 211 implantations of large-lumen, tunneled, central venous catheters. Insertions were performed under maximum sterile barrier in the angio suite using combined sonographic guidance for puncture of the internal jugular vein and fluoroscopy for placement of a triple lumen 12.5 F catheter (Hickman, BARD Murray Hill, NJ, USA). All interventions were performed under local anesthesia without need for anesthesiologic surveillance. Peri- and postinterventional complications were recorded using standardized international recommendations. RESULTS: Catheter implantation was technically successful in 207 of 211 cases (98.1%). Technical failure resulted in four patients due to chronic occlusions of the superior vena cava. No major complications were recorded. Four (1.9%) accidental arterial punctures occurred peri-interventionally; 24 (11.4%) early complications (bleeding, dysfunction, catheter rupture, and infection) and ten (4.7%) late complications (infection, dysfunction) were recorded. A clinically suspected catheter infection required catheter removal in 21 (10%) cases; 11 of 13 non-infectious catheter complications (bleeding, dysfunction, rupture) could be treated successfully by interventional-radiological treatment. CONCLUSION: Percutaneous implantation of large-lumen, tunneled, central venous catheters can be achieved with a high technical success rate and a low complication rate under combined sonographic and fluoroscopic guidance. In cases of mechanical complications, catheter rescue by interventional techniques is possible in the vast majority of cases.

The outcome of composite bone graft substitute used to treat cavitary bone defects.

Although autogenous bone graft remains the gold standard graft material, it is associated with an unacceptably high incidence of morbidity. Furthermore, operative time, blood loss, and length of hospitalization are often increased. In order for a graft substitute to replicate the optimal bone healing properties of autogenous graft, 3 essential elements must be present: scaffolding for osteoconduction, growth factors for osteoinduction, and progenitor cells for osteogenesis. A composite graft that combines a synthetic scaffold with osteoprogenitor cells from bone marrow aspirate (BMA) may potentially deliver the advantages of autogenous bone grafts without the procurement morbidity. Sixty consecutive patients with cavitary bone defects were treated with a composite of b-tricalcium phosphate (beta-TCP), Vitoss (Orthovita, Malvern, Pennsylvania), and BMA. The cavitary defects were measured on orthogonal views by experienced musculoskeletal radiologists. Radiographically, resorption and trabeculation increased steadily with time. This differential was slightly more noticeable in large defects with a central trabeculation occurring in advance of the peripheral region. The majority of patients progressed to unrestricted activities by 6 weeks and had returned to their usual activities by 12 weeks. No significant difference in graft incorporation rate was noted based on age, size of defect, or use of adjuvant local treatment. The use of a composite graft (ultraporous beta-TCP+BMA) in the treatment of cavitary lesions appears to be safe and effective.