Autologous micro-fragmented adipose tissue (MFAT) for the treatment of symptomatic knee osteoarthritis (OA) is gaining interest although there is still a lack of supportive data on safety and clinical efficacy. This study primarily aimed to identify patient- and pathology-related parameters to tighten patient selection criteria for future clinical MFAT application. Secondly, the overall (1) therapeutic response rate (TRR), (2) short-term clinical effect, (3) effect durability and (4) therapeutic safety was investigated at a minimal follow-up of 1 year. Sixty-four subjects (91 knees) with symptomatic knee OA (mild-severe on MRI) were enrolled in a prospective single-centre case series. Ethical approval was obtained from the local and academic ethical committee (#B300201733775). After liposuction, the adipose tissue was mechanically processed in a Lipogem® device which eventually produced 6–9cc MFAT. Subjects were clinically assessed by means of the KOOS, NRS, UCLA and EQ-5D at baseline and 1, 3, 6 and 12 months after injection. Adverse events were meticulously recorded. The TRR was defined according to the OMERACT-OARSI criteria. A baseline MRI was scored following the MOAKS system. Paired sample t-tests, independent t-test and Fischer's exact test were applied on appropriate variables. Multiple regression models were fit separately for patient-and pathology-specific factors. Significance level was set at α=0.05. The overall TRR was 66% at 3 months and 50% at 12 months after injection. Subgroup analysis revealed that specifically patients with no-mild bone marrow lesions (BML) had a TRR of 88% at 3 months and 75% at 12 months after MFAT injection. Therapy responders at these timepoints improved with 29.3±14.1 points and 30.8±15.3 points on KOOS pain, while non-responders deteriorated mildly. All clinical scores were significantly higher at follow-up compared to baseline (p<0.05). BMI (factor 0.17, p=0.002) and age (factor −0.48, p=0.048) were prognosticators for the TRR% at 1 month and for absolute KOOS pain improvement at 6 months, respectively. Posterior horn lesions (PHL) in the medial meniscus (p<0.001) and bone marrow lesions (p=0.003) were negative prognosticators for the TRR at respectively 6 and 12 months post-injection. An inflammatory reaction (pain, swelling or stiffness) to MFAT was reported in 79% knees and resolved spontaneously within 16.6±13.5 days after administration. The study showed a durable and satisfying TRR (up to 75% at 1 year in selected patients without BML) and clinical improvement after a single intra-articular injection with autologous MFAT. The availability of an index knee MRI is mandatory to select MFAT patients, preferably with no or mild BML and without PHL of the medial meniscus. High BMI and younger age are associated with better early outcomes. In comparison to other injection therapies such as cortisone, hyaluronic acid and PRP, MFAT appears very attractive with an effect durability of at least 1 year

Autologous tendon cell injection (ATI) is a promising non-surgical treatment for tendinopathies and tendon tear that address its underlying pathology. The procedure involves harvesting autologous tendon tissue, the isolation of the tendon cells, expansion under quality assured GMP cell laboratory and the injection of the tendon cells via U/S into the degenerative tendon tissue. In clinical practice, the patella (PT) and palmaris longus (PL) tendons are common sites used for tendon tissue biopsy. The objective of this study is to compare the tendon cell quality, identity, purity, doubling time and yield of cells between PT and PL tendons for ATI. Tendon tissue biopsies were harvested from PT via U/S using a 14-gauge needle or resected surgically from the PL tendon. The biopsies were transported to a GMP cell laboratory, where tendon cells were isolated, cultured and expanded for 4 to 6 weeks, and analysed for viability, cell doubling time, cellular characteristics including cell purity, potency and identity (PPI). Tendon samples from 149 patients were analysed (63 PT). Average biopsy weight was 62mg for PT and 119mg for PI (p<0.001). Average cell doubling time (83.9 vs 82.7 hours), cellular yield (16.2 vs 15.2x106), viability (98.7 vs 99.0%) and passage number (3 vs 3) were not significantly different between tendons. Additionally, ddPCR analyses showed no differences of PPI including tendon cell markers of collagen type I, scleraxis and tenomodulin. No post-biopsy complications or contamination were reported for either group. Assessing tendon tissue from palmaris tendon is relatively easier. Tendon tissue biopsy tissue for autologous tendon cell therapy can be obtained from either the PT or PL tendons. Tendon cells isolated from PT and PL were equal in growth characteristics and PPI. There are no differences in the quality of tendon cells isolated from the PT or PL

To test and evaluate the effectiveness of local injection of autologous fat-derived mesenchymal stem cells (MSCs) into fracture site to prevent non-union in a clinically relevant model. 5 male Wistar rats underwent the same surgical procedure of inducing non-union. A mid-shaft tibial osteotomy was made with 1mm non-critical gap. Periosteum was stripped around the two fracture ends. Then, the fracture was fixed by ante-grade intramedullary nail. The non-critical gap was maintained by a spacer with minimal effect on the healing surface area. At the same surgical time, subcutaneous fat was collected from the ipsilateral inguinal region and stem cells were isolated and cultured in vitro. Within three weeks postoperatively, the number of expanded stem cells reached 5×10. 6. and were injected into the fracture site. Healing was followed up for 8 weeks and the quality was measured by serial x-rays, microCT, mechanical testing and histologically. Quality of healing was compared with that of previously published allogenic, xenogeneic MSCs and Purified Buffered Saline (PBS) controls. All the five fractures united fully after 8 weeks. There was a progressive increase in the callus radiopacity during the eight-week duration, the average radiopacity in the autologous fat-MSC injected group was significantly higher than that of the allogeneic MSCs, xenogeneic MSCs and the control group, P < 0.0001 for treatment, time after injection, and treatment-time interaction (two-way repeated measure ANOVA). MicroCT, mechanical testing and histology confirmed radiological findings. The autologous fat-MSCs are effective in prevention of atrophic non-union by stimulation of the healing process leading to a solid union. The quality and speed of repair are higher than those of the other types of cell transplantation tested

Aneurysmal bone cyst (ABC) of the spine is a locally aggressive benign lesion which can be treated by en bloc resection with wide margin to reduce the risk of local recurrence. To avoid morbidity associated with surgery, selective arterial embolization (SAE) can be considered the first-line treatment for ABCs of the spine. We previously introduced the use of autologous bone marrow concentrate (BMC) injection therapy to stimulate bone healing and regeneration in ABC of the spine. In this prospective study we described the clinical and radiological outcomes of percutaneous injection of autologous BMC in a series of patients affected by ABCs of the spine. Fourteen patients (6 male, 8 female) were treated between June 2014 and December 2019 with BMC injection for ABC of the spine. The mean age was 17.85 years. The mean follow up was 37.4 months (range 12–60 months). The dimension of the cyst and the degree of ossification were measured by Computed Tomography (CT) scans before the treatment and during follow-up visits. Six patients received a single dose of BMC, five patients received two doses and in three patients three doses of BMC were administered. The mean ossification of the cyst (expressed in Hounsfield units) increased statistically from 43.48±2.36 HU to 161.71±23.48 HU during follow-up time and the ossification was associated to an improvement of the clinical outcomes. The mean ossification over time was significantly higher in patients treated with a single injection compared to patients treated with multiple injections. No significant difference in ossification was found between cervical and non-cervical localization of the cyst. Moreover, the initial size of the cyst was not statistically associated with the degree of ossification during follow-up. The results of this study reinforce our previous evidence on the use of BMC as a valid alternative for spinal ABC management when SAE is contraindicated or ineffective. The initial size of the cyst and its localization does not influence the efficacy of the treatment. However, data suggest that BMC injection could be indicated as treatment of choice for spinal ABC in young adolescent women

Introduction. Autologous Matrix Induced Chondrogenesis (AMIC) for surgical treatment of osteochondral lesions of the talus (OCLT) has shown excellent clinical and radiological results at short term follow up two years after surgery. However, no mid-term follow up data is available. Aim. 1. To evaluate the clinical outcome after AMIC-aided reconstruction of osteochondral lesions of the talus at a minimum follow up time of five years. 2. To evaluate the morphology and quality of the regenerated cartilage by magnetic resonance imaging (MRI) at on at a minimum follow up time of five years. Methods. Seventeen patients prospectively underwent surgery receiving a AMIC-aided repair of OCLT consisting of debridement, autologous grafting, and sealing of the defect with a collagen scaffold (Chondro-Gide, Geistlich Surgery, Wolhusen, Switzerland). Clinical and radiological assessment was performed before and after a minimum of 60 months after surgery (average 78 months, range, 60–120). Clinical examination included the American Orthopaedic Foot & Ankle Society (AOFAS) ankle score and the Visual Analogue Scale (VAS). Radiological imaging consisted of MRI. The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score was applied. Results. The AOFAS ankle score improved significantly from a mean of 60 points preoperatively (range, 17–79) to 91 points (range, 70–100) postoperatively (p< 0.01). The preoperative pain score averaged a VAS of 5 (range, 2–8), improving to an average of 1.1 (range 0–8) (p< 0.01). The MOCART score for cartilage repair tissue on postoperative MRI averaged 71 points (range, 50–90). Conclusion. The AMIC-procedure is safe for the treatment of OCLT with overall good clinical and magnetic resonance imaging results at five years follow up

Abstract. Objectives. The role of MSCs in enhancing healing has been examined with allogeneic and xenogeneic cells in transplantation models. However, certain factors might limit the use of allogeneic cells in clinical practice, (e.g. disease transmission, ethical issues and patient acceptance). Adipose tissue represents an abundant source for autologous cells. The aim of this study was to evaluate adipose-derived autologous cells for preventing non-union. Methods. Adults male Wistar rats (n=5) underwent a previously published surgical procedure known to result in non-union if no treatment is given. This consisted of a mid-shaft tibial osteotomy with peri/endosteal stripping stabilized by intramedullary nail fixation with a 1mm gap maintained by a spacer shown to have minimal effect on fracture healing. During the same operation, ipsilateral inguinal subcutaneous fat was harvested and processed for cell isolation. After three weeks in culture, the cell number reached 5 million and were injected into the fracture site. Results. At the end of the experiment, all tibias (injected with autologous fat-MSCs) developed union, 5/5. These were compared with a control group injected with PBS (n=4) and with allogenic (n=5) and xenogeneic (n=6) cell transplantation groups. The amount of callus was noticeably large in the autologous cell group and the distal-callus index was significantly greater than that of the other groups, P-value < 0.05, unpaired t-test, corrected by Benjamini & Hochberg. Conclusion. We report a novel method for autologous MSCs implantation to stimulate fracture healing. Local injection of autologous fat-MSCs into the fracture site resulted in a solid union in all the tibias with statistically significantly greater amounts of callus. Xenogeneic Bone Marrow and Fat derived MSCs have previously been shown to have similar effects (Tawonsawatruk et al. 2014), we show here that autologous MSCs were significantly better than the xenogenic MSCs at producing union. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Autologous cancellous bone graft is the gold standard in large bone defect repair. However, studies using autologous bone grafting in rats are rare and donor sites as well as harvesting techniques vary. The aim of this study was to determine the feasibility of autologous cancellous bone graft harvest from 5 different anatomical sites in rats and compare their suitability as donor sites for autologous bone graft. 13 freshly euthanised rats were used to describe the surgical approaches for autologous bone graft harvest from the humerus, iliac crest, femur, tibia and tail vertebrae (n=4), determine the cancellous bone volume and microstructure of those five donor sites using µCT (n=5), and compare their cancellous bone collected qualitatively by looking at cell outgrowth and osteogenic differentiation using an ALP assay and Alizarin Red S staining (n=4). It was feasible to harvest cancellous bone graft from all 5 anatomical sites with the humerus and tail being more surgically challenging. The microstructural analysis showed a significantly lower bone volume fraction, bone mineral density, and trabecular thickness of the humerus and iliac crest compared to the femur, tibia, and tail vertebrae. The harvested volume did not differ between the donor sites. All donor sites apart from the femur yielded primary osteogenic cells confirmed by the presence of ALP and Alizarin Red S stain. Bone samples from the iliac crest showed the most consistent outgrowth of osteoprogenitor cells. The tibia and iliac crest may be the most favourable donor sites considering the surgical approach. However, due to the differences in microstructure of the cancellous bone and the consistency of outgrowth of osteoprogenitor cells, the donor sites may have different healing properties, that need further investigation in an in vivo study

A new surgical hybrid technique involving the combination of autologous bone plug(s) and autologous chondrocyte implantation (AOsP-ACI) was used and evaluated as a treatment option in 15 patients for repair of large osteochondral defects in knee (N=12) and hip joints (N=3). Autologous Osplugs were used to contour the articular surface and the autologous chondrocytes were injected underneath a biological membrane covering the plug. The average size of the osteochondral defects treated was 4.5cm. 2. The average depth of the bone defect was 26mm. The patients had a significant improvement in their clinical symptoms at 12 months with significant increase in the Lysholm Score and Harris Hip Score (p = 0.031). The repaired tissue was evaluated using Magnetic Resonance Imaging, Computerised Tomography, arthroscopy, histology and immunohistochemistry (for expression of type I and II collagen). Magnetic Resonance Imaging, Computerised Tomography and histology at 12 months revealed that the bone plug became well integrated with the host bone and repair cartilage. Arthroscopic examination at 12 months revealed good lateral integration of the AOsP-ACI with the surrounding cartilage. Immunohistochemistry revealed mixed fibro-hyaline cartilage. We conclude that the hybrid AOsP-ACI technique provides a promising surgical approach for the treatment of patients with large osteochondral defects. This study highlights the use of this procedure in two different weightbearing joints and demonstrates good early results which are encouraging. The long term results need to be evaluated

Aim of study: Comparison of clinical and radiological results of the applied methods. Material and method: 20 patients with osteochondritis dissecans of the talus were treated. Autologous chondrocyte transplantation was applied to a group of 10 patients (Group A) and autologous osteochondral transplantation to the rest 10 patients (Group B).Group A: Average-age=30,8 years, -follow up time= 33,6 (12–48) months, -lesion size= 20×16,2 (35–15 × 25–15) mm and depth =7 (20–5) mmGroup B: Average –age =33, 7 years, follow up time =32,4 (12–48) months, – lesion size=16,5×15 (25–10 × 20–10) mm and depth=4 (5–3) mm.All patients underwent clinical und radiological investigation and the symptoms were classified in accordance with the Finsen classification. Group A was treated with autologous chondrocyte and Group B with autologous osteochondral transplantation. Osteotomy of the medial or lateral malleolus was necessary by 6 Group A – patients and 4 Group B – patients. Postoperative treatment : Non-weight bearing for 6 weeks, continuous passive motion of the joint, clinical and radiological follow up 3rd, 6th, 12th and yearly basis. Results: Postoperatively the average Finsen score showed for Group A an improvement from 3,5 (very bad) to 1,1 (excellent) and for Group B from 3,6 (very bad) to 1 (excellent). MRI follow up showed defect coverage by 7 patients of Group A and 9 patients of Group B after 12 months. Second look arthroscopy was performed by 4 patient of Group A and 3 patients of Group B showing full coverage of the defect site. Complications: persisting swelling for an average time of 2,7 months in Group A and 4,3 months in Group B. Additionally 10 degrees loss of joint extension in 4 patients of Group A and 3 patients of Group B. Conclusion: Autologous chondrocyte transplantation as well as autologous osteochondral transplantation present very good clinical results. As methods of articular surface restoration they have their advantages and disadvantages playing an important role in chosing one of them, in combination always with the surgeons philosophy. The existence of these methods is important in influencing the course of the ankle joint towards a good prognosis, in cases of osteochondral lesion. Further investigation is necessary

Stratification is required to ensure that only those patients likely to benefit, receive Autologous Chondrocyte Implantation (ACI); ideally by assessing a biomarker in the blood. This study aimed to assess differences in the plasma proteome of individuals who respond well or poorly to ACI. Isobaric tag for relative and absolute quantitation (ITRAQ) mass spectrometry and label-free proteomics analyses were performed in tandem as described previously by our group (Hulme et al., 2017; 2018; 2021) using plasma collected from ACI responders (n=10) compared with non-responders (n=10) at each stage of surgery (Stage I, cartilage harvest and Stage II, cell implantation). iTRAQ using pooled plasma detected 16 proteins that were differentially abundant at baseline in ACI responders compared with non-responders (n=10) (≥±2.0 fold; p<0.05). Responders demonstrated a mean Lysholm (patient reported functional score from 0–100) improvement of 33±13 and non-responders a mean worsening of −13±13 points. The most pronounced plasma proteome shift was seen in response to Stage I surgery in ACI non-responders, with 48 proteins being differentially abundant between the two surgical procedures. We have previously noted this marked shift in response to initial surgery in the SF of ACI non-responders, several of these proteins were associated with the Acute Phase Response. One of these proteins, clusterin, could be confirmed in patients’ plasma using an independent immunoassay using individual samples. Label-free proteomic data from individual samples identified only cartilage acidic protein-1 (known to associate with osteoarthritis progression) to be significantly more abundant at Stage I in the plasma of non-responders. This study indicates that proteins can be identified within the plasma that have potential use in ACI patient stratification. Further work is required to validate the findings of this discovery-phase work in larger ACI cohorts

Abstract. Introduction. The Syn-VAR RCT is the first of its kind comparing hamstrings autograft v synthetic neoligament for MPFL reconstruction. Our aim is to evaluate short and long term patient related outcomes measures (PROMs) following synthetic / autologous MPFL reconstruction in a heterogenous cohort of patients with recurrent patellar instability. Method. 20 patients meeting inclusion criteria were recruited and randomised. Standardised surgery was performed by a single surgeon in Altnagelvin Hospital with data collected over 3 years from 2016. Kujala score was the primary outcome measure with data captured preoperatively and 12 weeks/2 years postoperatively. Secondary outcomes included four other validated scores and complications including Norwich Patellar Instability, Lysholm, IKDC and Banff. Results. 20 patients with an average age of 19 included 9 females and 11 males. At 12 weeks and 2 years Kujala improvement in the hamstring group was 18 and 32 (both p<0.05) compared to the synthetic group where the increase was 2 and 20 (p<0.05). All secondary score improvements at 2 years were significant (p<0.05) with no difference in any score at all time intervals when comparing both groups (p<0.05). Discussion. Our RCT validates the non-inferiority of synthetic MPFL reconstruction as a treatment for restoring patellar stability in a small heterogenous group with positive long term data and minimal morbidity. With no hamstring harvesting offering a reduction in theatre time with this offers a safe, efficient and viable alternative with reduced morbidity

Our objective was to conduct a systematic review and meta-analysis, comparing differences in clinical outcomes between either autologous or synthetic bone grafts in the operative management of tibial plateau fractures: a traumatic pattern of injury, associated with poor long-term functional prognosis. A structured search of MEDLINE, EMBASE, The Bone & Joint and CENTRAL databases from inception until 07/28/2021 was performed. Randomised, controlled, clinical trials that compared autologous and synthetic bone grafts in tibial plateau fractures were included. Preclinical studies, clinical studies in paediatric patients, pathological fractures, fracture non-union or chondral defects were excluded. Outcome data was assessed using the Risk of Bias 2 (ROB2) framework and synthesised in random-effect meta-analysis. Preferred Reported Items for Systematic Review and Meta-Analysis guidance was followed throughout. Six comparable studies involving 352 patients were identified from 3,078 records. Following ROB2 assessment, five studies (337 patients) were eligible for meta-analysis. Within these studies, more complex tibia plateau fracture patterns (Schatzker IV-VI) were predominant. Primary outcomes showed non-significant reductions in articular depression at immediate postoperative (mean difference −0.45mm, p=0.25, 95% confidence interval (95%CI): −1.21-0.31mm, I. 2. =0%) and long-term (>6 months, standard mean difference −0.56, p=0.09, 95%CI: −1.20-0.08, I. 2. =73%) follow-up in synthetic bone grafts. Secondary outcomes included mechanical alignment, limb functionality, defect site pain, occurrence of surgical site infections, secondary surgery, perioperative blood loss, and duration of surgery. Blood loss was lower (90.08ml, p<0.001, 95%CI: 41.49-138.67ml, I. 2. =0%) and surgery was shorter (16.17minutes, p=0.04, 95%CI: 0.39-31.94minutes, I. 2. =63%) in synthetic treatment groups. All other secondary measures were statistically comparable. Our findings supersede previous literature, demonstrating that synthetic bone grafts are non-inferior to autologous bone grafts, despite their perceived disadvantages (e.g. being biologically inert). In conclusion, surgeons should consider synthetic bone grafts when optimising peri-operative patient morbidity, particularly in complex tibial plateau fractures, where this work is most applicable

The objectives of the study were to investigate demographic, injury and surgery/treatment-associated factors that could influence clinical outcome, following Autologous Chondrocyte Implantation (ACI) in a large, “real-world”, 20 year longitudinally collected clinical data set. Multilevel modelling was conducted using R and 363 ACI procedures were suitable for model inclusion. All longitudinal post-operative Lysholm scores collected after ACI treatment and before a second procedure (such as knee arthroplasty but excluding minor procedures such as arthroscopy) were included. Any patients requiring a bone graft at the time of ACI were excluded. Potential predictors of ACI outcome explored were age at the time of ACI, gender, smoker status, pre-operative Lysholm score, time from surgery, defect location, number of defects, patch type, previous operations, undergoing parallel procedure(s) at the time of ACI, cell count prior to implantation and cell passage number. The best fit model demonstrated that for every yearly increase in age at the time of surgery, Lysholm scores decreased by 0.2 at 1-year post-surgery. Additionally, for every point increase in pre-operative Lysholm score, post-operative Lysholm score at 1 year increased by 0.5. The number of cells implanted also impacted on Lysholm score at 1-year post-op with every point increase in log cell number resulting in a 5.3 lower score. In addition, those patients with a defect on the lateral femoral condyle (LFC), had on average Lysholm scores that were 6.3 points higher one year after surgery compared to medial femoral condyle (MFC) defects. Defect grade and location was shown to affect long term Lysholm scores, those with grade 3 and patella defects having on average higher scores compared to patients with grade 4 or trochlea defects. Some of the predictors identified agree with previous reports, particularly that increased age, poorer pre-operative function and worse defect grades predicted poorer outcomes. Other findings were more novel, such as that a lower cell number implanted and that LFC defects were predicted to have higher Lysholm scores at 1 year and that patella lesions are associated with improved long-term outcomes cf. trochlea lesions

The role of mesenchymal stem cells (MSCs) in enhancing healing process has been examined with allogeneic and xenogeneic cells in transplantation models. However, certain factors might limit the use of allogeneic cells in clinical practice, (e.g. disease transmission, ethical issues and patient acceptance). Adipose tissue represents an abundant source for autologous cells. The aim of this study was to evaluate adipose-derived autologous cells for preventing non-union. Adults male Wistar rats (n=5) underwent a previously published surgical procedure known to result in non-union if no treatment is given. This consisted of a mid-shaft tibial osteotomy with peri/endosteal stripping stabilised by intramedullary nail fixation with a 1mm gap maintained by a spacer. During the same operation, ipsilateral inguinal subcutaneous fat was harvested and processed for cell isolation. After three weeks in culture, the cell number reached 5×106 and were injected into the fracture site. At the end of the experiment, all tibias (injected with autologous fat-MSCs) developed union. These were compared with a control group injected with PBS (n=4) and with allogenic (n=5) and xenogeneic (n=6) cell transplantation groups. The amount of callus was noticeably large in the autologous cell group and the distal-callus index was significantly greater than that of the other groups, P-value =<0.05, unpaired t-test, corrected by Benjamini & Hochberg. We report a novel method for autologous MSCs implantation to stimulate fracture healing. Local injection of autologous fat-MSCs into the fracture site resulted in a solid union in all the tibias with statistically significantly greater amounts of callus

Introduction and Objective. Aneurysmal bone cyst (ABC) of the spine is a locally aggressive benign lesion which can be treated by en bloc resection with wide margin to reduce the risk of local recurrence. To avoid morbidity associated with surgery, selective arterial embolization (SAE) can be considered the first-line treatment for ABCs of the spine. Other emerging treatments for ABCs include bisphosphonates, percutaneous doxycycline, sclerotherapy and Denosumab. In addition, we previously introduced the use of autologous bone marrow concentrate (BMC) injection therapy to stimulate bone healing and regeneration in ABC of the spine. One of the potential advantages of such a method is that surgical treatments are not necessary, thus allowing for both a minimally invasive approach and the treatment of poorly accessible lesions. In this prospective study we described the clinical and radiological outcomes of percutaneous injection of autologous BMC in a series of patients affected by ABCs of the spine and followed for at least one year. Materials and Methods. Fourteen patients (6 male, 8 female) were treated between June 2014 to December 2019 with BMC injection for ABC of the spine. The mean age was 17.85 years. The mean follow up was 37.4 months (range 12– 60 months). The dimension of the cyst and the degree of ossification were measured by Computed Tomography (CT) scans before the treatment and during follow-up visits. Results. Six patients received a single dose of BMC, five patients received two doses and in three patients three doses of BMC were administered. The mean ossification of the cyst (expressed in Hounsfield units) increased statistically from 43.48±2.36 HU to 161.71±23.48 HU during follow-up time and the ossification was associated to an improvement of the clinical outcomes. The mean ossification over time was significantly higher in patients treated with a single injection compared to patients treated with multiple injections. No significant difference in ossification was found between cervical and non-cervical localization of the cyst. Moreover, the initial size of the cyst was not statistically associated with the degree of ossification during follow-up. We also observed that five out of six female patients (83.3%) were less than sixteen years old and four of these (66.7%) were managed with a single dose of BMC injection, while a higher percentage of male patients (6/8, 75%) were more than sixteen years old and more than one injection was administered to them. Conclusions. The results of this study reinforce our previous evidence on the use of BMC as a valid alternative for spinal ABC management when SAE is contraindicated or ineffective. The initial size of the cyst and its localization does not influence the efficacy of the treatment. However, BMC injection could be indicated as treatment of choice for spinal ABC in young adolescent women

Post-traumatic osteonecrosis of the femoral head (ONFH) is a major complication of femoral neck fractures that require numerous solutions. The purpose of the current study is to investigate the effects of platelet-rich plasma (PRP) incorporated autologous granular bones graft for the treatment of pre-collapse stages (ARCO stage II-III) of post-traumatic ONFH. A total of 46 patients were eligible and enrolled into the study. 24 patients were treated with core decompression and PRP incorporated autologous granular bones graft (treatment group: 9 females and 15 males, age range, 16–39 years), and 22 patients with core decompression and autologous granular bones graft (control group: 6 females and 16 males, age range, 18–42 years. During a minimum duration of follow-up of 36 months, multiple imaging techniques including X-ray and computed tomography (CT) scanning were used to evaluate the radiological results, and Harris hip score (HHS) and the visual analogue scale (VAS) were chosen to assess the clinical results. Both treatment group and control group had a significant improved HHS (P < 0.001). The minimum clinically important difference (MCID) for HHS was reached in 91.7% of treatment group and 68.2% of control group (P = 0.0449). HHS in treatment group was significantly higher than control group at the last follow-up (P = 0.0254). VAS score was significantly declined in treatment group when compared with control group (P = 0.0125). Successful clinical results were achieved in 21 of 24 patients (87.5%) in treatment group compared with 13 of 22 patients (59.1%) in control group (P = 0.0284). Successful radiological results were achieved in 19 of 24 patients (79.2%) in treatment group compared with 11 of 22 patients (50%) in control group (P = 0.0380). The survival rates using requirement for further hip surgery as an endpoint were higher in treatment group in comparison to control group (P = 0.0260). The PRP incorporated autologous granular bones graft is a safe and effective procedure for the treatment of pre-collapse stages (ARCO stage II-III) of post-traumatic ONFH

Due to the presence of megakaryocytes, platelets and clotting factors, bone marrow aspirate (BMA) tends to coagulate. For the first time, starting from our previous studies on mesenchymal vertebral stem cells, it has been hypothesized that coagulated BMA represents a safe and effective autologous biological scaffold for bone regeneration in spinal surgery. The present research involved advanced preclinical in vitro models and the execution of a pilot clinical study. Evaluation of cell morphology, growth kinetics, immunophenotyping, clonogenicity, trilineage-differentiation, growth-factors and HOX and TALE gene expression were analyzed on clotted- and un-clotted human V-BMA. In parallel, a pilot clinical study on ten patients with degenerative spine diseases submitted to instrumented posterior arthrodesis, is ongoing to assess the ability of clotted-V-BMA to improve spinal fusion at 6- and 12-months follow-up. Results demonstrated that clotted-V-BMA have significantly higher growth-factor expression and mesenchymal stem cell (MSCs) viability, homogeneity, clonogenicity, and ability to differentiate towards the osteogenic phenotype than un-clotted-V-BMA. Clotted-V-BMA also highlighted significant reduced expression of PBX1 and of MEIS3 genes negatively involved in osteoblast maturation and differentiation. From December 2020, eight patients have already been enrolled with first promising results that will be finally evaluated in the next two months. The application of V-BMA-clot as carrier of progenitors and cytokines and as natural scaffold with a structural texture represents a point-of-care orthobiologic product to improve spinal fusion. Clinical application seems to be efficacy, and we will confirm and strengthen these data with the final results of the pilot clinical study

Introduction. Meniscus deficiency leads to the development of early arthritis. Total knee replacement may be the only available treatment option in certain situations. However it is generally best avoided in young patients. We hypothesized that a combination of the two procedures, Allograft Meniscal Transplantation (AMT) and Autologous Chondrocyte Implantation (ACI) would be a solution to treat bone-on-bone arthritis in meniscal deficient knees and postpone the need for a total knee replacement (TKR). Materials/Methods. 12 consecutive patients who underwent both ACI and AMT between 1998 and 2005 were followed up prospectively. The patients were assessed by a self-assessed Lysholm score prior to the procedure and yearly thereafter. All operations were performed by the senior author (JBR). ACI procedure was performed according to the standard technique. Frozen meniscal allograft with bone plugs at either ends secured by sutures in the bone tunnels. Post operatively all patients underwent a strict Oscell Rehabilitation protocol. A repeat procedure or progression to a TKR was taken as a failure. Results. Out of the twelve patients only eleven were included as one had died at three months after surgery. Three patients had delayed TKR, and two were heading towards TKR at 8 years. The median pre-operative lysholm score in the remaining six patients rose from 45 to 64 at last follow up. Conclusions. In our small pilot study there was a 19 point increase in the lysholm score. The combination of ACI & AMT could give a good result defer the need for TKR

Deriving autologous mesenchymal stem cells (MSCs) from adipose tissues without using enzymes requires sophisticated biomedical instruments. Applied pressure on tissues and cells are adjusted manually although centrifugation and filtration systems are frequently used. The number of derived MSCs therefore could differ between instruments. We compared the number of MSCs obtained from four commercially available devices and our newly designed and produced instrument (A2, B3, L3, M2 and T3). Three-hundred mL of adipose tissue was obtained from a female patient undergoing liposuction using the transillumination solution. Obtained tissue was equally distributed to each device and handled according to the producers' guides. After handling, 3 mL stromal vascular fraction (SVF) was obtained from each device. Freshly isolated SVF was characterized using multi-color flow cytometry (Navios Flow Cytometer, Beckman Coulter, USA). Cell surface antigens were chosen according to IFATS and ISCT. CD31-FITC, CD34-PC5,5, CD73-PE, CD90-PB and CD45-A750 (Backman Coulter, USA) fluorochrome-labeled monoclonal antibodies were assessed. Markers were combined with ViaKrome (Beckman Coulter, USA) to determine cell viability. At least 10. 5. cells were acquired from each sample. A software (Navios EX, Beckman Coulter, USA) was used to create dot plots and to calculate the cell composition percentages. The data was analyzed in the Kaluza 2.1 software package (Beckman Coulter, USA). Graphs were prepared in GraphPad Prism. CD105 PC7/CD31 FITC cell percentages were 23,9%, 13,5%, 24,6%, 11,4% and 28,8% for the A2, B3, L3, M2 and T3 devices, respectively. We conclude that the isolated MSC percentage ranged from 11,4% to 28,8% between devices. The number of MSCs in SVF are key determinants of success in orthobiological treatments. Developing a device should focus on increasing the number of MSCs in the SVF while preserving its metabolic activity. Acknowledgments: Scientific and Technological Research Council of Türkiye (TÜBİTAK)- Technology and Innovation Funding Program Directorate (TEYDEB) funded this project (#321893). Servet Kürümoğlu and Bariscan Önder of Disposet Ltd., Ankara, Türkiye (. www.disposet.com. ) contributed to the industrial design and research studies. Ali Tuncel and Feza Korkusuz are members of the Turkish Academy of Sciences (TÜBA). Nilsu Baysal was funded by the STAR Program of TÜBITAK Grant # 3210893

Interstitial supraspinatus tears can cause persistent subacromial impingement symptoms despite non operative treatment. Autologous tendon cell injection (ATI) is a non-surgical treatment for tendinopathies and tear. We report a randomised controlled study of ATI compared to corticosteroid injection (CS) as treatment for interstitial supraspinatus tears and tendinopathy. Inclusion criteria were patients with symptom duration > 6 months, MRI confirmed intrasubstance supraspinatus tear, and prior treatment with physiotherapy and ≥ one CS or PRP injection. Participants were randomised to receive ATI to the interstitial tear or corticosteroid injection to the subacromial bursa in a 2:1 ratio, under ultrasound guidance. Assessments of pain (VAS) and function (ASES) were performed at baseline, and 1, 3, 6 and 12 months post treatment. 30 participants (19 randomised to ATI) with a mean age of 50.5 years (10 females) and a mean duration of symptoms of 23.5 months. Baseline VAS pain and ASES scores were comparable between groups. While mean VAS pain scores improved in both groups at 3 months after treatment, pain scores were superior with ATI at 6 months (p=0.01). Mean ASES scores in the ATI group were superior to the CS group at 3 months (p=0.026) and 6 months (p=0.012). Seven participants in the CS group withdrew prior to 12 months due to lack of improvement. At 12 months, mean VAS pain in the ATI group was 1.6 ± 1.3. The improvements in mean ASES scores in the ATI group at 6 and 12 months were greater than the MCID (12.0 points). At 12 months, 95% of ATI participants had an ASES score > the PASS (patient acceptable symptom state). This is the first level one study using ATI to treat interstitial supraspinatus tear. ATI results in a significant reduction in pain and improvement in shoulder function