• BMAC
• Bone-marrow aspirate concentrate
• Hip osteoarthritis
• Orthobiologics
• Regenerative medicine

• Autologous orthobiologics
• Bone marrow concentrate (BMC)
• Cell therapy
• Exercise therapy
• Musculoskeletal pain
• Platelet-rich plasma (PRP)
• Rotator cuff tears
• Shoulder

• Humans
• Male
• Female
• Rotator Cuff Injuries/therapy
• Rotator Cuff Injuries/diagnostic imaging
• Middle Aged
• Cross-Over Studies
• Exercise Therapy/methods
• Bone Marrow Transplantation/methods
• Aged
• Follow-Up Studies
• Treatment Outcome
• Rotator Cuff/diagnostic imaging
• Rotator Cuff/surgery
• Pain Measurement
• Adult
• Patient Reported Outcome Measures
• Magnetic Resonance Imaging

• Bayesian network meta-analysis
• Bone marrow aspirate concentrate
• Femoral head necrosis
• Regenerative therapies
• Stem cells

• Humans
• Femur Head Necrosis/surgery
• Femur Head/surgery
• Network Meta-Analysis
• Bayes Theorem
• Arthroplasty, Replacement, Hip
• Treatment Outcome

• no.2023JH2/101600029 The Science and Technology Plan of Liaoning Province of China
• no.21-174-9-03 Shenyang Municipal Bureau of Science and Technology

• KOOS
• VAS
• osteoarthritis
• stromal-vascular fraction

Radiofrequency energy is a common treatment modality for chronic pain. While there are different forms of radiofrequency-based therapeutics, the common concept is the generation of an electromagnetic field in the applied area, that can result in neuromodulation (pulsed radiofrequency—PRF) or ablation. Our specific focus relates to PRF due to the possibility of modulation that is in accordance with the mechanisms of action of orthobiologics. The proposed mechanism of action of PRF pertaining to pain relief relies on a decrease in pro-inflammatory cytokines, an increase in cytosolic calcium concentration, a general effect on the immune system, and a reduction in the formation of free radical molecules. The primary known properties of orthobiologics constitute the release of growth factors, a stimulus for endogenous repair, analgesia, and improvement of the function of the injured area. In this review, we described the mechanism of action of both treatments and pertinent scientific references to the use of the combination of PRF and orthobiologics. Our hypothesis is a synergic effect with the combination of both techniques which could benefit patients and improve the life quality.

• Calcium
• Chronic Pain/therapy
• Cytokines
• Humans
• Pain Management/methods
• Pulsed Radiofrequency Treatment/methods
• Treatment Outcome

• Cell therapy
• Regenerative medicine
• Safety
• Stem cells
• Tendinopathy
• Tendons

There has been increasing evidence and growing popularity of orthobiologic treatments, such as platelet-rich plasma, bone marrow aspirate concentrate, and microfragmented adipose tissue. However, real-world data, including patient-reported pain and function outcomes, remains sparse for these procedures. Thus, collecting patient-reported outcome measures is important to evaluate the safety and efficacy of these treatments and hopefully improve patient care. Patient reported outcome measures can systematically be collected through patient registries. This narrative review serves to describe the data collection platforms and registries that obtain patient-reported outcome measures on orthobiologic procedures and provide a discussion on the benefits and limitations of registries. An internet search of the list of orthopedic registries available was conducted, and registries that collect patient-reported outcome measures for orthobiologic procedures were identified. Additional information regarding these various registries was collected by directly contacting these vendors. Publications from these registries, including case series, observational studies, and annual reports, were also reviewed. Providing this review will inform clinicians of a digital tool that can increase the efficiency of collecting outcome measures for orthobiologics and aid physicians in choosing a data collection platform.

• Musculoskeletal Conditions
• Orthobiologics
• Outcomes Assessment/Measurement

To compare the efficacy of a single, intra-articular, nonconcentrated bone marrow aspirate (BMA) injection in comparison to cortisone for the treatment of glenohumeral joint osteoarthritis (GHJ OA).

Inclusion criteria were patients between the ages of 18 and 75 with a diagnosis of GHJ OA on radiograph. Patients were randomized to receive an ultrasound-guided, intra-articular cortisone injection or BMA injection (without concentration). The primary outcome measure was the Western Ontario Osteoarthritis of the Shoulder (WOOS) index at 12 months. Secondary outcome measures were the QuickDASH, EuroQOL 5-dimensions 5-level questionnaire (EQ-5D-5L) and visual analogue scale.

The study included 25 shoulders of 22 patients who completed baseline and 12 months’ patient-reported outcome measures (12 shoulders received cortisone, 13 shoulders received BMA) after the study was terminated early by changes in Health Canada regulations. Baseline characteristics demonstrated a significant difference in the ages of the 2 groups, with the BMA group being older (61.6 vs 53.8 mean years, P = 0.021). For the BMA group, a significant improvement was seen in the WOOS index (P = 0.002), the QuickDASH (P < 0.001), and the EQ-5D-5L pain dimension (P = 0.004) between baseline and 12 months. No significant difference was seen for any outcome in the cortisone group between baseline and 12 months. No significant difference was demonstrated between changes in the WOOS scores from baseline to 12 months when compared between groups (P = 0.07). However, a significant difference in changes in scores was seen in the QuickDASH (P = 0.006) and the EQ-5D-5L pain scores (P = 0.003) and the EQ-5D-5L health scores (P = 0.032) in favor of BMA.

The results of this study demonstrate that patients with GHJ OA treated with BMA have superior changes in the QuickDASH and EQ-5D-5L pain and health scores but not in the WOOS outcomes measures at 12 months post injection when compared to patients treated with cortisone. However, because of the limited number of patients as a result of the early termination of the study, larger randomized studies are required to confirm these findings.

Level II, randomized controlled trial.

• Cell-based therapies
• epicondylitis
• msc
• rotator cuff pathology
• sports injuries
• tenocytes

• Elbow
• Orthobiologics
• PRP
• Shoulder
• Stem cells

To evaluate the time required for colonies to develop from concentrated bone marrow aspirate (cBMA) and subacromial bursal tissue samples.

Samples of cBMA and subacromial bursa tissue were harvested from patients undergoing rotator cuff repair surgery between November 2014 and December 2019. Samples were analyzed for time to form colonies and number of colonies formed. The impact of age, sex, and cellularity (cBMA only) was analyzed. Samples were cultured and evaluated daily for colony formation in accordance with the guidelines of the International Society for Cellular Therapy. Demographic factors were analyzed for impact on time to form colonies and number of colonies formed.

Samples of cBMA were obtained from 92 patients. Subacromial bursa tissue was obtained from 54 patients. For cBMA, older age was associated with more days to form colonies (P = .003), but sex (P = .955) and cellularity (P = .623) were not. For bursa, increased age was associated with longer time to form colonies (P = .002) but not sex (P = .804). Conclusions: Increased age (in cBMA and subacromial bursa tissue) and lower initial cellularity (in cBMA) are associated with longer time to form colonies in culture.

Although connective tissue progenitor cells are widely used in orthopaedic practice, there are few metrics to determine their efficacy. Time to form colonies may serve as an important measurement for determining connective tissue progenitor cell viability for augmentation of rotator cuff repair. Subacromial bursa tissue may represent a viable alternative to cBMA for augmentation of rotator cuff repair, capable of forming colonies expediently in vivo.

To investigate the available literature on the use of bone marrow aspirate concentrate (BMAC) and summarize the current evidence supporting its potential for the injective treatment of joints affected by osteoarthritis (OA).

A systematic literature search was conducted on three electronic databases (PubMed, Embase, and Cochrane Library) in April 2020, using the following string: “((bone marrow concentrate) OR (BMC) OR (bone marrow aspirate concentrate) OR (BMAC)) AND (osteoarthritis)”, and inclusion criteria: clinical and preclinical (animal) studies of any level of evidence, written in English language, and evaluating the intra-articular or subchondral use of BMAC for the injective treatment of OA joints.

The publication trend remarkably increased over time. A total of 22 studies were included in the qualitative data synthesis: four preclinical studies and 18 clinical studies, for a total number of 4626 patients. Safety was documented by all studies, with a low number of adverse events. An overall improvement in pain and function was documented in most of the studies, but the clinical studies present significant heterogeneity, few patients, short-term follow-up, and overall poor methodology.

There is a growing interest in the field of BMAC injections for the treatment of OA, with promising results in preclinical and clinical studies in terms of safety and effectiveness. Nevertheless, the current knowledge is still preliminary. Preclinical research is still needed to optimize BMAC use, as well as high-level large controlled trials to better understand the real potential of BMAC injections for the treatment of patients affected by OA.

• BMAC
• Bone marrow concentrate
• Cartilage
• Injective
• Intra-articular
• Osteoarthritis

• Bone-marrow aspirate concentrate
• Bone-marrow classification
• Musculoskeletal disorders
• Orthobiologics
• Regenerative medicine
• Stem cells

• Platelet Rich Plasma (PRP)
• Stem Cells
• mesenchymal stromal cells (MSCs)
• orthobiologics
• orthopedic medicine
• regenerative medicine
• regenerative rehabilitation

Injectable regenerative therapies such as bone marrow concentrate (BMC) and platelet-rich plasma (PRP) may represent a safe alternative in the treatment of rotator cuff tears. This is a midterm review of a randomized, crossover trial comparing autologous BMC and platelet product injections versus exercise therapy in the treatment of partial and full-thickness supraspinatus tears. Patients enrolled into the study were between 18 and 65 years of age presenting to an outpatient orthopedic clinic with partial to full thickness, nonretracted supraspinatus tendon tears. Enrolled patients were randomized to either ultrasound-guided autologous BMC with PRP and platelet lysate (PL) percutaneous injection treatment or exercise therapy. Patients could cross over to BMC treatment after at least 3 months of exercise therapy. Patients completed the Disability of the Arm, Shoulder and Hand (DASH) scores as the primary outcome measure. Secondary outcomes included the numeric pain scale (NPS), a modified Single Assessment Numeric Evaluation (SANE), and a blinded MRI review. At this midterm review, results from 25 enrolled patients who have reached at least 12-month follow-up are presented. No serious adverse events were reported. Significant differences were seen in patient reported outcomes for the BMC treatment compared to exercise therapy at 3 and 6 months for pain, and for function and reported improvement (SANE) at 3 months (p < .05). Patients reported a mean 89% improvement at 24 months, with sustained functional gains and pain reduction. MRI review showed a size decrease of most tears post-BMC treatment. These findings suggest that ultrasound-guided BMC and platelet product injections are a safe and useful alternative to conservative exercise therapy of torn, nonretracted supraspinatus tendons. This trial is registered with NCT01788683.

• Mesenchymal Stem Cells
• Tendon and Ligament injures

• Mesenchymal stem cell
• Orthobiologics
• Regenerative medicine
• Stem cell

• bone marrow aspirate concentrate
• bone marrow concentrate
• cartilage defect
• cells
• diagnosis
• mesenchymal stem cells
• osteoarthritis

• Clinical outcomes
• quality
• regenerative medicine
• registry

• clinical trials
• growth factors
• mechanical stimulation
• rotator cuff regeneration
• small molecules
• stem cells
• synthetic and biologic scaffolds

• bmac
• stem cells
• bone marrow aspirate concentrate
• tendon
• tendinopathy

• bone marrow aspirate concentrate
• bmac
• mesenchymal stem cells

The combination of cells with platelet-rich plasma (PRP) may fulfill tendon deficits and help overcome the limited ability of tendons to heal.

To examine the suitability of 3 human cell types in combination with PRP and the potential impact of the tenocyte-conditioned media (CM) to enhance tendon healing.

Controlled laboratory study.

Tenocytes, bone marrow–derived mesenchymal stem cells, and skin fibroblasts were cultured in 3-dimensional PRP hydrogels supplemented or not with CM, and cell proliferation and migration were examined. The effect of tendon-derived CM on matrix-forming phenotype and secretion of inflammatory proteins was determined through their administration to mesenchymal stem cells, tendon, and skin fibroblasts by reverse transcription quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively.

Differences were found in the matrix-forming phenotype between each of the cell types. The ratio of collagen I:collagen III was greater in bone marrow–derived mesenchymal stem cells than in skin fibroblasts and tenocytes. The bone marrow–derived mesenchymal stem cells expressed increased levels of cartilage-related genes than tenocytes or skin fibroblasts. The presence of the tenocyte-CM stimulated basic healing mechanisms including proliferation and chemotaxis in all cell types. In addition, the tenocyte-CM modified the matrix-forming phenotype of every cell type when cultured in PRP hydrogels. Each cell type secreted interleukin-6, interleukin-8, and monocyte chemotactic protein-1 in PRP hydrogels, but mesenchymal stem cells secreted less interleukin-8 and monocyte chemotactic protein-1 than tenocytes or skin fibroblasts.

The tenocyte-CM combined with PRP stimulated tenogenesis in mesenchymal stem cells and in skin fibroblasts and reduced the secretion of inflammatory proteins.

Modifying the target tissue with PRP prior to cell implantation may optimize the effect of cell therapies. Skin fibroblasts and bone marrow–derived mesenchymal stem cells combined with PRP could be used to regenerate tendons.

• cell therapy
• mesenchymal stem cells
• platelet-rich plasma
• tendinopathy