Effectiveness and Complications of Bone Marrow Aspirate Concentrate in Patients with Knee Osteoarthritis of Kellgren-Lawrence Grades II-III.

This study aimed to identify the effectiveness and potential complications on the harvest site and knee of bone marrow aspirate concentrate (BMAC) treatment of patients with Kellgren-Lawrence (K-L) grades II-III knee osteoarthritis (OA) over a minimum follow-up period of 6 months. This study retrospectively evaluated data from 231 patients (285 knees) with knee OA treated with BMAC articular injection at a single center from August 2023 to October 2023. The inclusion criteria were a longstanding knee pain unresponsive to conservative treatments for at least 6 weeks with K-L grades II-III OA. The exclusion criteria were age of <40 years or >80 years, previous knee surgery, rheumatological or other systemic disease, malignancy, uncontrolled diabetes mellitus, or infections. Bone marrow was aspirated from the anterior iliac crest and concentrated by the single-spin centrifugation technique. The visual analog scale (VAS) pain score and Knee Society Score were used to evaluate the clinical outcomes and complications associated with harvest and injection sites were evaluated. The mean follow-up period was 7.2 months (range: 6-8 months). The pretreatment VAS pain score decreased from 4.3 to 0.4 points at the final follow-up (p < 0.05). Pretreatment Knee Society knee and function scores were improved from 86.9 to 98.1 (p < 0.05) and from 68.4 to 83.3 points (p < 0.05), respectively. A total of 15 complications (5.3%, 15/285) were observed, including 3 hematomas, 2 numbness, 2 contact dermatitis, and 1 superficial infection in the harvest site and 4 mild and moderate swelling and 3 severe swelling and pain in the injection site. BMAC is a reliable and effective treatment for patients with K-L grades II-III knee OA, but the orthopedic surgeon should consider that bleeding tendency by heparin causes severe joint swelling and pain after intra-articular knee injection.

Bone marrow aspirate concentrate quality is affected by age and harvest site.

PURPOSE: To compare the number and properties of bone marrow stromal cells (BMSCs) collected from bone marrow aspirate concentrate (BMAC) obtained from different harvest sites and from patients of different ages. METHODS: BMAC was obtained from two groups of patients based on age (n = 10 per group): 19.0 ± 2.7 years for the younger and 56.8 ± 12.5 for the older group. In the latter, BMAC was obtained from both iliac crest and proximal tibia for a donor-matched analysis. Mononucleated cell count and CFU-F assay were performed, together with phenotype characterization of BMSCs from iliac crest and proximal tibia, the study of chondrogenic and osteogenic differentiation capacity, histological staining and spectrophotometric quantification, and the analysis of mRNAs expression. RESULTS: Cells derived from iliac crest and proximal tibia showed the same phenotypic pattern at flow cytometry, as well as similar chondrogenic and osteogenic potential. However, a significantly higher number of mononuclear cells per ml was observed in younger patients (3.8 ± 1.8 × 107) compared to older patients (1.2 ± 0.8 × 107) (p < 0.0005). The latter yield, obtained from the iliac crest, was significantly higher than resulting from the BMAC harvested from the proximal tibia in the same group of patients (0.3 ± 0.2 × 107, p < 0.0005). This result was confirmed by the CFU-F analysis at day 10 (15.9 ± 19.4 vs 0.6 ± 1.0, p = 0.001) and day-20 (21.7 ± 23.0 vs 2.9 ± 4.2, p = 0.006). CONCLUSION: Harvest site and age can affect the quality of BMAC. BMSCs obtained from iliac crest and proximal tibia present comparable mesenchymal markers expression as well as osteogenic and chondrogenic differentiation potential, but iliac crest BMAC presents a four times higher number of mononucleated cells with significantly higher clonogenic capacity compared to the tibia. BMAC of younger patients also had a three-time higher number of mononucleated cells. The identification of BMAC characteristics could help to optimize its preparation and to identify the most suitable indications for this orthobiologic treatment in the clinical practice.

Combined subchondral and intra-articular injections of bone marrow aspirate concentrate provide stable results up to 24 months.

PURPOSE: The aim of this study was to evaluate the clinical and imaging findings up to 24 months of follow-up in patients treated with combined subchondral and intra-articular bone marrow aspirate concentrate (BMAC) injections for the treatment of knee osteoarthritis (OA). METHODS: Thirty consecutive patients (19 males, 11 females) aged between 40 and 75 years (mean age 56.4 ± 8.1 years) with unilateral symptomatic knee OA (Kellgren-Lawrence 2-3) were included in the study. Patients were treated with combined intra-articular and subchondral bone BMAC injections (total 9 ml) under fluoroscopic control. IKDC subjective score, VAS for pain, KOOS, and EQ-VAS were prospectively evaluated up to 24 months. Radiographs were performed at baseline and at 24 months after the procedure. MRI was evaluated with the WORMS score at baseline, 6-12 months, and 24 months of follow-up. The statistical analysis was performed using SPSS v.19.0 and for all tests p < 0.05 was considered significant. RESULTS: No major complications and a 13% failure rate were reported. The IKDC subjective score remained stable from 62.6 ± 19.4 at 12 months to 63.4 ± 17.1 at 24 months (both p < 0.0005 compared to baseline, 40.5 ± 12.5). Similar improvements were reported for all KOOS subscales, while EQ-VAS did not report any significant improvement. VAS pain worsened from 3.0 ± 1.9 at 12 months to 4.4 ± 1.8 at the final follow-up (p = 0.0001), although remaining lower compared to the baseline value of 6.3 ± 1.8 (p = 0.002). The radiographic evaluation did not reveal signs of improvement or deterioration of the OA grade. The MRI findings showed a worsening in marginal osteophytes and synovitis, but a significant reduction of bone marrow edema at 24 months (p < 0.0005). CONCLUSION: Combined intra-articular and subchondral BMAC injections provided clinical and imaging benefits up to 24 months for the treatment of symptomatic knee OA, with durable clinical results, a low failure rate, and a significant reduction of bone marrow edema.

Limited evidence in support of bone marrow aspirate concentrate as an additive to the bone marrow stimulation for osteochondral lesions of the talus: a systematic review and meta-analysis.

PURPOSE: Bone marrow aspirate concentrate can be used as an additive to surgical treatment of osteochondral lesions of the talus. This systematic literature review aims to study the effect of the additional use of bone marrow aspirate concentrate on top of a surgical treatment for osteochondral lesions of the talus on clinical outcomes compared to surgical treatment alone. METHODS: An online literature search was conducted using PubMed (Medline), Embase (Ovid), and the Cochrane library for all studies comparing a surgical intervention with bone marrow aspirate concentrate, with a surgical intervention without bone marrow aspirate concentrate. The methodological quality was rated according to the methodological index for non-randomised studies checklist. The primary outcome measure were clinical outcomes. Secondary outcome measures consisted of revision rate, complication rate, radiographic outcome measures and histological analyses. Subgroups were created based on type of surgical intervention used in the studies. If multiple articles were included in a subgroup, a linear random-effects model was used to compare the bone marrow aspirate concentrate-augmented group with the control group. RESULTS: Out of 1006 studies found, eight studies with a total of 718 patients were included. The methodological quality, assessed according to the methodological index for non-randomised studies checklist, was weak. A significantly better functional outcome measures (p < 0.05) was found in the subgroup treated with bone marrow stimulation + bone marrow aspirate concentrate compared to the group treated with bone marrow stimulation alone, based on three non-blinded studies. No significant differences regarding clinical outcomes were found in the subgroups comparing matrix-induced autologous chondrocyte implantation with matrix-induced bone marrow aspirate concentrate, osteochondral autologous transplantation alone with osteochondral autologous transplantation + bone marrow aspirate concentrate and autologous matrix-induced chondrogenesis plus peripheral blood concentrate vs. matrix-associated stem cell transplantation bone marrow aspirate concentrate. CONCLUSION: There is insufficient evidence to support a positive effect on clinical outcomes of bone marrow aspirate concentrate as an additive to surgical treatment of osteochondral lesions of the talus. However, based on the safety reports and initial results, sufficiently powered, patient- and researcher-blinded, prospective randomised controlled trials are justified and recommended. Until then, we advise not to implement a therapy (addition of bone marrow aspirate concentrate) without clinical evidence that justifies the additional costs involved. LEVEL OF EVIDENCE: Level III.

Hyaluronic scaffold transplantation with bone marrow concentrate for the treatment of osteochondral lesions of the talus: durable results up to a minimum of 10 years.

PURPOSE: The aim of this study was to evaluate the long-term clinical results of the transplantation of a hyaluronic acid membrane augmented with bone marrow aspirate concentrate (BMAC) in an one-step technique for the treatment of patients affected by osteochondral lesions of the talus (OLT). METHODS: A total of 101 patients (64 men, 37 women, age 32.9 ± 10.9) were evaluated for a minimum of 10 years of follow-up (151.5 ± 18.4 months) The mean lesion size was 2.2 ± 1.4 cm2, the lesion had a post-traumatic origin in 73 patients, 15 patients previously had an ankle fracture, 22 patients had ankle osteoarthritis. All patients were clinically evaluated at baseline and at 2, 5, and a minimum of 10 years after treatment using the AOFAS score, the NRS for pain, and the Tegner score. A survival analysis was performed to check the survival to failure up to the last follow-up. RESULTS: The AOFAS score significantly improved from baseline (59.6 ± 13.9) to the final follow-up (82.3 ± 14.2) (p < 0.0005). A significant reduction in the AOFAS score was found from 2 to 10 years (p < 0.0005). The NRS for pain changed from 7.0 ± 1.3 at baseline to 3.9 ± 2.7 at the final follow-up (p < 0.0005). A significant worsening was documented between 5 years and the final follow-up (p < 0.0005). The Tegner score improved from the preoperative value of 2.0 (range 1-7) to 3.0 (range 1-7) at the final follow-up (p < 0.0005), although it remained lower as compared to the preinjury level of 4.0 (range 1-9) (p < 0.0005). Better results were documented in male and younger patients with smaller lesions, without the previous surgery, and without the previous ankle fractures or osteoarthritis. At the final follow-up, 85 patients considered their general health status "satisfactory" and 84 patients reported feeling "better" than the preoperative condition. Five patients were considered failures and underwent prosthetic ankle replacement or repeated the same surgery. CONCLUSION: This one-step technique showed to be an effective procedure for the treatment of OLT, providing a low failure rate and offering durable clinical improvements up to a minimum of 10 years of follow-up. However, this technique demonstrated a small yet significant decrease over the years in terms of pain and function and poor results in terms of sports activity level. LEVEL OF EVIDENCE: Level IV.

Orthobiologics: a review.

PURPOSE: The use of biologic materials in orthopaedics (orthobiologics) has gained significant attention over the past years. To enhance the body of the related literature, this review article is aimed at summarizing these novel biologic therapies in orthopaedics and at discussing their multiple clinical implementations and outcomes. METHODS: This review of the literature presents the methods, clinical applications, impact, cost-effectiveness, and outcomes, as well as the current indications and future perspectives of orthobiologics, namely, platelet-rich plasma, mesenchymal stem cells, bone marrow aspirate concentrate, growth factors, and tissue engineering. RESULTS: Currently available studies have used variable methods of research including biologic materials as well as patient populations and outcome measurements, therefore making comparison of studies difficult. Key features for the study and use of orthobiologics include minimal invasiveness, great healing potential, and reasonable cost as a nonoperative treatment option. Their clinical applications have been described for common orthopaedic pathologies such as osteoarthritis, articular cartilage defects, bone defects and fracture nonunions, ligament injuries, and tendinopathies. CONCLUSIONS: Orthobiologics-based therapies have shown noticeable clinical results at the short- and mid-term. It is crucial that these therapies remain effective and stable in the long term. The optimal design for a successful scaffold remains to be further determined.

Meniscus repair via collagen matrix wrapping and bone marrow injection: clinical and biomolecular study.

PURPOSE: The functional outcomes of arthroscopic matrix-based meniscus repair (AMMR) in patients two and five years after the treatment clearly show that the use of the collagen matrix and bone marrow aspirate creates favorable biological conditions for meniscus healing. This study not only provides ten follow-up results but also investigates biomolecular mechanisms governing the regenerative process. METHODS: Case series was based on data collected from patients who underwent AMMR procedure, starting with preoperatively through two-year and five-year till ten-year follow-up. The outcomes are presented as IKDC and the Lysholm subjective scores as well as the imaging results. Biomolecular investigation of the membranes utilized in the AMMR procedure include DNA content analysis, cell viability and proliferation study of bone marrow and bone marrow concentrate-derived cells, and cytokine array performed on monocytes cultured on the membranes. CONCLUSION: Data collected from patients who underwent AMMR procedure, starting with pre-operatively through two year and five year till ten year follow-up, indicate the possibility for long-term, stable meniscus preservation. Outcomes are manifested with a visible improvement of the IKDC and the Lysholm subjective scores as well as in the imaging results. The type of the meniscal tear or complexity of the knee injury (isolated AMMR vs. AMMR + ACL) did not affect the clinical outcomes. The study highlighted the role of the membrane in facilitating cell adhesion and proliferation. Additionally, several cytokines were selected as potentially crucial products of the membrane vs. monocyte interactions, driving the tissue regeneration and remodeling. Interestingly, thresholds of what constitutes a safe and well-decellularized membrane according to relevant literature have been significantly breached, but ultimately did not elicit detrimental side effects.

Cytokine Dynamics in Autism: Analysis of BMAC Therapy Outcomes.

Autism spectrum disorder (ASD) has recently been linked to neuroinflammation and an aberrant immune response within the central nervous system. The intricate relationship between immune response and ASD remains elusive, with a gap in understanding the connection between specific immune mechanisms and neural manifestations in autism. In this study, we employed a comprehensive statistical approach, fusing both overarching and granular methods to examine the concentration of 16 cytokines in the cerebrospinal fluid (CSF) across each autologous bone marrow aspirate concentrate (BMAC) intrathecal administration in 63 male and 17 female autism patients. Following a six-month period post the third administration, patients were stratified into three categories based on clinical improvement: Group 1- no/mild (28 subjects), Group 2-moderate (16 subjects), and Group 3-major improvement (15 subjects). Our integrated analysis revealed pronounced disparities in CSF cytokine patterns and clinical outcomes in autism subjects pre- and post-BMAC transplantation. Crucially, our results suggest that these cytokine profiles hold promise as predictive markers, pinpointing ASD individuals who might not exhibit notable clinical amelioration post-BMAC therapy.

Bone Marrow Aspirate Concentrate versus Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells for Combined Cartilage Regeneration Procedure in Patients Undergoing High Tibial Osteotomy: A Systematic Review and Meta-Analysis.

Background and objectives: Cartilage regeneration using mesenchymal stem cells (MSCs) has been attempted to improve articular cartilage regeneration in varus knee osteoarthritis (OA) patients undergoing high tibial osteotomy (HTO). Bone marrow aspirate concentrate (BMAC) and human umbilical cord blood-derived MSCs (hUCB-MSCs) have been reported to be effective. However, whether BMAC is superior to hUCB-MSCs remains unclear. This systematic review and meta-analysis aimed to determine the clinical efficacy of cartilage repair procedures with BMAC or hUCB-MSCs in patients undergoing HTO. Materials and Methods: A systematic search was conducted using three global databases, PubMed, EMBASE, and the Cochrane Library, for studies in which the clinical outcomes after BMAC or hUCB-MSCs were used in patients undergoing HTO for varus knee OA. Data extraction, quality control, and meta-analysis were performed. To compare the clinical efficacy of BMAC and hUCB-MSCs, reported clinical outcome assessments and second-look arthroscopic findings were analyzed using standardized mean differences (SMDs) with 95% confidence intervals (CIs). Results: The present review included seven studies of 499 patients who received either BMAC (BMAC group, n = 169) or hUCB-MSCs (hUCB-MSC group, n = 330). Improved clinical outcomes were found in both BMAC and hUCB-MSC groups; however, a significant difference was not observed between procedures (International Knee Documentation Committee score; p = 0.91, Western Ontario and McMaster Universities OA Index; p = 0.05, Knee Society Score (KSS) Pain; p = 0.85, KSS Function; p = 0.37). On second-look arthroscopy, the hUCB-MSC group showed better International Cartilage Repair Society Cartilage Repair Assessment grade compared with the BMAC group (p < 0.001). Conclusions: Both BMAC and hUCB-MSCs with HTO improved clinical outcomes in varus knee OA patients, and there was no difference in clinical outcomes between them. However, hUCB-MSCs were more effective in articular cartilage regeneration than BMAC augmentation.

An exploratory clinical trial for concentrated autologous bone marrow aspirate transplantation in the treatment of osteonecrosis of the femoral head.

PURPOSE: This study evaluated the efficacy and safety of a novel treatment for osteonecrosis, in which concentrated autologous bone marrow aspirate transplantation (CABMAT) is followed by low-intensity pulsed ultrasound (LIPUS) stimulation for 3 months. The study was designed as a prospective, uncontrolled, open-label phase II clinical study. METHODS: This study included 16 cases of osteonecrosis of the femoral head (ONFH), including 26 hips. Patients were transplanted with concentrated bone marrow and periodically evaluated for infection and neoplasm development. Moreover, clinical and radiological examinations were conducted to confirm the treatment efficacy. RESULTS: No infections were observed during the course of this study nor tumours developed at the treatment site 24 months after transplantation. At a mean 48 (30-56) months post-transplantation, the onset or progression of collapse was noted in four hips, of which one hip underwent total hip arthroplasty. CONCLUSION: Treatment with CABMAT combined with 3-month LIPUS stimulation was safe, and further randomised clinical studies are needed to determine the efficacy and feasibility of this treatment. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN000020940, 9/2/2016).

Thematic trend mapping and hotspot analysis in bone marrow aspirate concentrate therapy: A scientometric literature analysis and advances in osteoarthritis.

Bone marrow aspirate concentrate (BMAC) therapy has been spotlighted as a promising regenerative tool with its abundant source of mesenchymal stromal cells (MSCs) and growth factors. The spectrum of the utility of BMAC therapy has been expanding day by day to harness the potential for varied therapeutic purposes. In the due course of its evolution, it is often essential to have a comprehensive summary of progress to have a greater understanding and refine our future directives. With technological developments such as data mining, graphic drawing and information analytics combined with computational statistics, visualization of scientific metrology has become a reality. With this newer perspective, we intend to use scientometric tools including text mining, cocitation analysis, keyword analysis and cluster network analysis to perform thematic trend mapping and hotspot analysis of the literature on BMAC therapy and evaluate its progress in the management of osteoarthritis.

Bone marrow aspirate concentrate versus platelet-rich plasma for treating knee osteoarthritis: a one-year non-randomized retrospective comparative study.

BACKGROUND: Knee osteoarthritis (OA) is a debilitating condition affecting human body biomechanics and quality of life. Current standard care for knee OA leads to trivial improvement and entails multiple adverse effects or complications. Recently, investigational cell therapies injected intra-articularly, such as bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP), have shown safety and therapeutic potency providing patients with pain relief. In the current retrospective comparative study, we investigated the differences in pain and functional improvements in patients with symptomatic knee OA receiving intra-articular injections of BMAC vs PRP. METHODS: Pain and functionality scores were measured at baseline and at different time points post-injection over 12 months, using 3 self-administered, clinically validated questionnaires: the visual analogue scale (VAS) for assessing pain intensity, the knee injury and osteoarthritis outcome score (KOOS) for evaluating functionality and knee-related quality of life, and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) for evaluating physical function. The repeated-measures general linear model with Sidak test for pairwise comparisons was used to investigate the influence of the treatment on the score evolution within groups (between baseline and each time point) and between groups (overall). RESULTS: The BMAC group (n = 26 knees) significantly improved in VAS, KOOS, and WOMAC scores between baseline and 12 months (57.4, 75.88, and 73.95% mean score improvement, respectively). In contrast, the PRP group (n = 13 knees) witnessed nonsignificant improvement in all scores. BMAC, in comparison to PRP, induced significant improvement in outcomes by 29.38% on the VAS scale, 53.89% on the KOOS scale, and 51.71% on the WOMAC scale (P < .002, P < .01, P < .011, respectively). CONCLUSIONS: Intra-articular autologous BMAC injections are safe, effective in treating pain, and ameliorate functionality in patients with symptomatic knee OA to a greater extent than PRP injections. Intra-articular autologous BMAC therapy is safe and provides more relief to patients with symptomatic knee osteoarthritis compared to PRP therapy.

Blood in the joint: effects of hemarthrosis on meniscus health and repair techniques.

Injury to the meniscus is common and frequently leads to the development of post-traumatic osteoarthritis (PTOA). Many times meniscus injuries occur coincident with anterior cruciate ligament (ACL) injuries and lead to a bloody joint effusion. Hemarthrosis, or bleeding into the joint, has been implicated in degeneration of joint tissues. The goal of this review paper is to understand the pathophysiology of blood-induced joint damage, the possible effects of blood on meniscus tissue, and the implications for current meniscus repair techniques that involve the introduction of blood-derived products into the joint. In this review, we illustrate the similarities in the pathophysiology of joint damage due to hemophilic arthropathy (HA) and osteoarthritis (OA). Although numerous studies have revealed the harmful effects of blood on cartilage and synovium, there is currently a gap in knowledge regarding the effects of hemarthrosis on meniscus tissue homeostasis, healing, and the development of PTOA following meniscus injury. Given that many meniscus repair techniques utilize blood-derived and marrow-derived products, it is essential to understand the effects of these factors on meniscus tissue and the whole joint organ to develop improved strategies to promote meniscus tissue repair and prevent PTOA development.

Bone marrow aspirate concentration provided better results in cartilage regeneration to microfracture in knee of osteoarthritic patients.

PURPOSE: To determine whether microfracture with bone marrow aspirate concentrate (BMAC) improves functional outcome and cartilage regeneration better than microfracture alone in patients undergoing high tibial osteotomy (HTO) for medial unicompartmental osteoarthritis (OA). METHODS: Among 436 patients treated with HTO for medial unicompartmental OA with varus deformity between 2010 and 2016, clinical outcomes were retrospectively compared between the microfracture alone group (group I, 43 cases) and microfracture with BMAC augmentation group (group II, 48 cases). Of these, 64 patients underwent a second-look arthroscopic assessment. Clinical outcomes were compared based on the Knee Society Score (KSS), International Knee Documentation Committee (IKDC) subjective score, and Western Ontario and McMaster Universities Arthritis Index (WOMAC). Cartilage regeneration was assessed according to Koshino's staging system and the International Cartilage Repair Society (ICRS) Cartilage Repair Assessment (CRA) grading system. RESULTS: At the last follow-up, there were no significant intergroup differences in terms of KSS for pain and function (p > 0.05). Moreover, WOMAC scores were similar between the two groups (p > 0.05). Regarding second-look arthroscopy findings, according to Koshino's staging system, there was no significant intergroup difference in terms of defect coverage (p = 0.187). However, group II showed a significantly better mean CRA score than group I (p = 0.035). CONCLUSION: There were no significant differences in clinical outcomes and cartilage regeneration between the groups. However, the CRA score was significantly higher with BMAC augmentation and microfracture than microfracture alone. Therefore, BMAC augmentation had a synergistic effect for a better cartilage regeneration, although studies with a longer follow-up might help to confirm whether microfracture with BMAC augmentation would ensure better clinical outcomes than microfracture alone for the treatment of knee OA.

Modified Kerboul Angle Predicts Outcome of Core Decompression With or Without Additional Cell Therapy.

BACKGROUND: Core decompression is the most common procedure for early-stage osteonecrosis of the femoral head (ONFH). This study investigated outcomes of core decompression with/without bone marrow aspirate concentrate (BMAC), based on the Kerboul combined necrotic angles using magnetic resonance imaging. METHODS: We reviewed 66 patients (83 hips) with early ONFH, Association Research Circulation Osseous stages I-IIIa, who underwent core decompression alone (26 patients, 33 hips) or in combination with BMAC (40 patients, 50 hips). Survival rate and progressive collapse were analyzed using the Kaplan-Meier method, and conversion to total hip arthroplasty (THA) was evaluated. Subgroup analyses based on the modified Kerboul angle were performed: grade I (<200°), grade II (200°-249°), grade III (250°-299°), and grade IV (≥300°). RESULTS: Mean follow-up was 36 ± 23 months. Femoral head collapse with BMAC (16 hips, 32%) was significantly lower than without BMAC (19 hips, 58%, P = .019). Conversion THA was significantly lower with BMAC (28%) than without (58%, P = .007). Survival rates among groups showed significant differences (P = .017). In grade I, 0/12 hips with BMAC collapsed while 3/9 (33%) without BMAC collapsed (P = .063); in grade II, 2/16 hips (12%) with BMAC collapsed while 7/13 (54%) without BMAC collapsed (P = .023). There was no significant difference in collapse with (64%) or without (82%) BMAC in grade III-IV hips (P = .256). CONCLUSION: Core decompression with/without BMAC had a high failure rate, by increasing disease progression and the necessity for THA, for combined necrotic angles >250°. In our study, addition of BMAC had more reliable outcomes than isolated core decompression for precollapse ONFH if the combined necrotic angles were <250°.

Intra-articular gold induced cytokine (GOLDIC®) injection therapy in patients with osteoarthritis of knee joint: a clinical study.

PURPOSE: To evaluate the safety and efficacy of a novel technique of preconditioning autologous blood with gold particles (GOLDIC®) and injection in patients with moderate to severe knee osteoarthritis (KOA). METHODS: During this phase 2a, proof-of-concept (PoC) open label study, 83 consecutive patients that 64 patients met inclusion criteria (mean age: 64.8 years; 89 knees) with radiographically proven KOA, received four ultrasound guided intra-articular knee injections of GOLDIC® at three to six day intervals. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee injury and Osteoarthritis Outcome Score (KOOS) were evaluated at baseline, four weeks, three, six months, one, two and four years (T1-T6). The incidence of treatment related severe adverse events (SAEs) recorded. Intra-articular gelsolin level in patients with effusion was determined. RESULTS: KOOS and WOMAC scores improved for the full duration of the study (P < 0.05), minimal clinically important difference (MCID) was observed at all time points in all KOOS subscores, with no reported SAEs. Intra-articular gelsolin level increased after treatment with reduction of effusion. No statistically significant evidence of an association between patient demographics and outcome were identified. Nine patients failed treatment, with 32 months mean time to failure and underwent total knee arthroplasty. CONCLUSION: PoC study of GOLDIC® as a novel device for conservative management of moderate to severe KOA was confirmed. GOLDIC® produces rapid and sustained improvements in all indices after treatment, with no SAEs. TRIAL REGISTRATION: § 13 Abs.2b AMG Bavaria (Protokol Reg OBB 5-16) (Ref 53.2-2677.Ph_3-67-2)-Date 3/20/2010 retrospectively registered.

Bone Marrow Aspirate Concentrate versus Platelet Rich Plasma or Hyaluronic Acid for the Treatment of Knee Osteoarthritis.

Background: In the last decade, regenerative therapies have become one of the leading disease modifying options for treatment of knee osteoarthritis (OA). Still, there is a lack of trials with a direct comparison of different biological treatments. Our aim was to directly compare clinical outcomes of knee injections of Bone Marrow Aspirate Concentrate (BMAC), Platelet-rich Plasma (PRP), or Hyaluronic acid (HA) in the OA treatment. Methods: Patients with knee pain and osteoarthritis KL grade II to IV were randomized to receive a BMAC, PRP, and HA injection in the knee. VAS, WOMAC, KOOS, and IKDC scores were used to establish baseline values at 1, 3, 6, 9, and 12 months. All side effects were reported. Results: A total of 175 patients with a knee osteoarthritis KL grade II-IV were randomized; 111 were treated with BMAC injection, 30 with HA injection, and 34 patients with PRP injection. There were no differences between these groups when considering KL grade, BMI, age, or gender. There were no serious side effects. The mean VAS scores after 3, 7, 14, and 21 days showed significant differences between groups with a drop of VAS in all groups but with a difference in the BMAC group in comparison to other groups (p < 0.001). There were high statistically significant differences between baseline scores and those after 12 months (p < 0.001) in WOMAC, KOOS, KOOS pain, and IKDC scores, and in addition, there were differences between these scores in the BMAC group in comparison with other groups, except for the PRP group in WOMAC and the partial IKDC score. There were no differences between the HA and PRP groups, although PRP showed a higher level of clinical improvement. Conclusions: Bone marrow aspirate concentrate, Leukocyte rich Platelet Rich Plasma, and Hyaluronic acid injections are safe therapeutic options for knee OA and provide positive clinical outcomes after 12 months in comparison with findings preceding the intervention. BMAC could be better in terms of clinical improvements in the treatment of knee OA than PRP and HA up to 12 months. PRP provides better outcomes than HA during the observation period, but these results are not statistically significant. More randomized controlled trials and high quality comparative studies are needed for direct correlative conclusions.

Cryopreserved bone marrow aspirate concentrate as a cell source for the colony-forming unit fibroblast assay.

PURPOSE: The prevalence of connective tissue progenitor cells within a cell-based therapy is often quantified using the colony-forming unit fibroblast (CFU-F) assay. The present study investigates the feasibility of using cryopreserved bone marrow aspirate concentrate (BMAC) as an alternative cell source to fresh BMAC for CFU-F quantification. METHODS: Freshly prepared and corresponding cryopreserved BMAC samples from patients receiving autologous cell therapy (n = 98) were analyzed using the CFU-F assay for comparison. Cultures were established by directly plating BMAC at low cell densities and maintained for a 2-week growth period. Colonies were enumerated to determine CFU-F frequency, and a subset of cultures was imaged and analyzed to quantify colony area and density. RESULTS: A nonlinear relationship was observed between plating density and CFU-F frequency over a wide range in plating densities (~30-fold). Cryopreserved BMAC yielded recoverable (77 ± 23%) and viable (73 ± 9%) nucleated cells upon thawing. After cryopreservation, CFU-F frequencies were found to be significantly lower (56.6 ± 34.8 vs. 50.3 ± 31.7 colonies per million nucleated cells). Yet the number of CFU-F in fresh and cryopreserved BMAC were strongly correlated (r = 0.87) and had similar area and densities. Further, moderate correlations were observed between the number of CFU-F and nucleated cells, and both the mean colony area and density were negatively correlated with patient age. Notably, no relationship was found between CFU-F frequency and age, regardless of whether fresh or cryopreserved BMAC was used. CONCLUSIONS: Freshly prepared and cryopreserved BMAC yielded correlated results when analyzed using the CFU-F assay. Our findings support the cryogenic storage of patient BMAC samples for retrospective CFU-F analyses, offering a potential alternative for characterizing BMAC and furthering our understanding of progenitor cells in relation to clinical outcome.

Effectiveness of bone marrow aspirate concentrate (BMAC) as adjuvant therapy in the surgical treatment of congenital pseudoarthrosis of the tibia: a retrospective comparative study.

Congenital pseudoarthrosis of the tibia (CPT) is a rare disease characterised by the onset of bone anomalies or fractures, leading to deformities in paediatric patients. The aetiology of this pathology is unknown. The main theories include the presence of hamartomatous tissue related to Neurofibromatosis type 1, vascularisation deficit of the periosteum and alterations in the numbers and functions of the osteoblasts and osteoclasts in loco. Surgical treatment generally requires multiple operations during the patient's childhood and adolescence. The best outcomes seem to occur when using intramedullary nailing, vascularised fibular transplant and external fixation with the Ilizarov technique. The purpose of this paper is to evaluate the effectiveness of in-situ injections of Bone Marrow Aspirate Concentrate (BMAC) as an adjuvant therapy for congenital pseudoarthrosis of the tibia in patients treated with external fixation and that of radiographic healing over time compared to external fixation treatment alone. We performed a retrospective review of clinical and radiographic records of patients affected by CPT and treated in the Paediatric Orthopaedics and Traumatology Department of the Gaetano Pini Orthopaedic Institute with in-situ injections of bone marrow aspirate concentrate (BMAC) on the pseudoarthrosis site, in addition to pseudoarthrosis site excision and application of circular external fixator frame in compression (Group A). The time needed to reach the radiological consolidation of the resection site was recorded and compared to that needed for patients treated with only pseudoarthrosis site excision and application of circular external fixator frame in compression (Group B). There is a statistically relevant improvement of healing time in patients affected by congenital pseudoarthrosis of the tibia treated with external fixation and bone marrow aspirate concentrate compared to patients affected by the same pathology treated with external fixation only. Injection of MSC in the pseudoarthrosis site after focus removal in combination with circular external fixation achieves faster bone healing compared with external fixation only, and the lower refracture percentage may be associated with the better quality and structure of the new bone. However, it would be desirable to have a longer followup to determine if the results of the BMC as adjuvant therapy will hold up over time.

Epidemiology, Clinical Assessments, and Current Treatments of Nonunions.

PURPOSE OF REVIEW: The failure of bony union following a fracture, termed a fracture nonunion, has severe patient morbidity and economic consequences. This review describes current consensuses and future directions of investigation for determining why, detecting when, and effective treatment if this complication occurs. RECENT FINDINGS: Current nonunion investigation is emphasizing an expanded understanding of the biology of healing. This has led to assessments of the immune environment, multiple cytokines and morphogenetic factors, and the role of skeletogenic stem cells in the development of nonunion. Detecting biological markers and other objective diagnostic criteria is also a current objective of nonunion research. Treatment approaches in the near future will likely be dominated by the development of specific adjunct therapies to the nonunion surgical management, which will be informed by an expanded mechanistic understanding of nonunion biology. Current consensus among orthopedists is that improved diagnosis and treatment of nonunion hinges first on discoveries at the bench side with later translation to the clinic.