Rotator cuff tears are common in middle-aged and elderly patients. Despite advances in the surgical repair of rotator cuff tears, the rates of recurrent tear remain high. This may be due to the complexity of the tendons of the rotator cuff, which contributes to an inherently hostile healing environment. During the past 20 years, there has been an increased interest in the use of biologics to complement the healing environment in the shoulder, in order to improve rotator cuff healing and reduce the rate of recurrent tears. The aim of this review is to provide a summary of the current evidence for the use of forms of biological augmentation when repairing rotator cuff tears. Cite this article:
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
Disease modifying approaches are commonly applied in OA patients. An aging society with better life expectancies is increasing in Europe and the globe. Orthobiologics cover intraarticular hyaluronan injections and also cellular therapies. Cellular therapies range from platelet rich plasma (PRP) applications to exosomes. Short term follow-up of limited number of patients revealed favorable results in clinical cellular therapies. Most of these studies evaluated decrease of pain and increase in function. Recent basic science studies focused on the action mechanism of
Aims. The aim of this study was to establish consensus statements on the diagnosis, nonoperative management, and indications, if any, for medial patellofemoral complex (MPFC) repair in patients with patellar instability, using the modified Delphi approach. Methods. A total of 60 surgeons from 11 countries were invited to develop consensus statements based on their expertise in this area. They were assigned to one of seven working groups defined by subtopics of interest within patellar instability. Consensus was defined as achieving between 80% and 89% agreement, strong consensus was defined as between 90% and 99% agreement, and 100% agreement was considered to be unanimous. Results. Of 27 questions and statements on patellar instability, three achieved unanimous consensus, 14 achieved strong consensus, five achieved consensus, and five did not achieve consensus. Conclusion. The statements that reached unanimous consensus were that an assessment of physeal status is critical for paediatric patients with patellar instability. There was also unanimous consensus on early mobilization and resistance training following nonoperative management once there is no apprehension. The statements that did not achieve consensus were on the importance of immobilization of the knee, the use of
Introduction. Osteochondral lesions (OCLs) of the talus are a challenging and increasingly recognized problem in chronic ankle pain. Many novel techniques exist to attempt to treat this challenging entity. Difficulties associated with treating OCLs include lesion location, size, chronicity, and problems associated with potential graft harvest sites. Matrix associated stem cell transplantation (MAST) is one such treatment described for larger lesions >15mm2 or failed alternative therapies. This cohort study describes a medium-term review of the outcomes of talar lesions treated with MAST. Methods. A review of all patients treated with MAST by a single surgeon was conducted. Preoperative radiographs, MRIs and FAOS outcome questionnaire scores were conducted. Intraoperative classification was undertaken to correlate with imaging. Postoperative outcomes included FAOS scores, return to sport, revision surgery/failure of treatment and progression to arthritis/fusion surgery. Results. 58 MAST procedures in 57 patients were identified in this cohort. The mean follow up was 5 years. There were 20 females and37males, with a mean age of 37 years (SD 9.1). 22 patients had lateral OCLS were and 35 patients had medial OCLs. Of this cohort 32patients had previous surgery and 25 had this procedure as a primary event. 15 patients had one failed previous surgery, 9 patients had two, four patients had three previous surgeries and three patients had four previous surgeries. 12 patients had corrective or realignment procedures at the time of surgery. In terms of complications 3 patients of this cohort went on to have an ankle fusion and two of these had medial malleolar metal work taken out prior to this, 5 patients had additional procedures for arthrofibrotic debridements, 1 patient had a repeat MAST procedure, 1 additional patients had removal of medial malleolar osteotomy screws for pain at the osteotomy site, there were 2 wound complications one related to the ankle and one related to pain at the iliac crest donor site. Conclusion. MAST has demonstrated positive results in lesions which prove challenging to treat, even in a “ failed microfracture” cohort. RCT still lacking in field of
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
Platelet-rich plasma (PRP) intra-articular injections may provide a simple and minimally invasive treatment for early-stage knee osteoarthritis (OA). This has led to an increase in its adoption as a treatment for knee OA, although there is uncertainty about its efficacy and benefit. We hypothesized that patients with early-stage symptomatic knee OA who receive multiple PRP injections will have better clinical outcomes than those receiving single PRP or placebo injections. A double-blinded, randomized placebo-controlled trial was performed with three groups receiving either placebo injections (Normal Saline), one PRP injection followed by two placebo injections, or three PRP injections. Each injection was given one week apart. Outcomes were prospectively collected prior to intervention and then at six weeks, three months, six months, and 12 months post-intervention. Primary outcome measures were Knee Injury and Osteoarthritis Outcome Score (KOOS) and EuroQol five-dimension five-level index (EQ-5D-5L). Secondary outcomes included visual analogue scale for pain and patient subjective assessment of the injections.Aims
Methods
Geriatric syndromes could lead individuals to exhibit significant mobility and psychological deficits resulting in significant healthcare costs. Thus, identifying strategies to delay aging, or prevent progressive loss of tissue homeostasis could dramatically restore the function and independence of millions of elderly patients and significantly improve quality of life. One of the fundamental properties of aging is the accumulation of senescent cells and senescence associated secretory phenotypes (SASPs) that needs to be treated in wide range of therapeutics including
Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone. The ovine femoral condyle model was used. Bone marrow was aspirated, concentrated, and used intraoperatively with a collagen/hydroxyapatite scaffold to fill the osteochondral defects (n = 6). Tissue regeneration was then assessed versus the scaffold-only group (n = 6). Histological staining of cartilage with alcian blue and safranin-O, changes in chondrogenic gene expression, microCT, peripheral quantitative CT (pQCT), and force-plate gait analyses were performed. Lymph nodes and blood were analyzed for safety.Aims
Methods
Abstract. Objectives. The development of promising therapeutics for cartilage repair/regeneration have been hampered by the inadequacy of existing animal models and lack of suitable translational ex-vivo human tissue models. There is an urgent unmet need for these to assess repair/regenerative (orthobiologic) treatments directly in human tissue. We describe methodology allowing the successful long-term ex-vivo culture of non-degenerate whole human femoral heads that may be used as a model for testing new
Surgical repair of rotator cuff tears have high failure rates (20–70%), often due to a lack of biological healing. Augmenting repairs with extracellular matrix-based scaffolds is a common option for surgeons, although to date, no commercially available product has proven to be effective. In this study, a novel collagen scaffold was assessed for its efficacy in augmenting rotator cuff repair. The collagen scaffold was assessed in vitro for cytocompatability and retention of tenocyte phenotype using alamarBLUE assays, confocal imaging and real-time PCR. Immunogenicity was assessed in vitro by the activation of pre-macrophage cells. In vivo, using a modified rat rotator cuff defect model, supraspinatus tendon repairs were carried out in 46 animals. Overlay augmentation with the collagen scaffold was compared to unaugmented repairs. At 6- and 12-weeks post-op the repairs were tested biomechanically to evaluate repair strength, and histologically for quality of healing. The collagen scaffold supported human tenocyte growth in vitro, with cells appearing morphologically tenocytic and expressing higher tendon gene markers compared to plastic controls. No immunogenic responses were provoked compared to suture material control. In vivo, augmentation with the scaffold improved the histological scores at 12 weeks (8.37/15 vs. 6.43/15, p=0.0317). However, no significant difference was detected on mechanical testing. While the collagen scaffold improved the quality of healing of the tendon, a meaningful increase in biomechanical strength was not achieved. This is likely due to its inability to affect the bone-tendon junction. Future materials/
Bone is a dynamic organ with remarkable regenerative properties seen only otherwise in the liver. However, bone healing requires vascularity, stability, growth factors, a matrix for growth, and viable cells to obtain effective osteosynthesis. We rely on these principles not only to heal fractures, but also achieve healing of benign bone defects. Unfortunately we are regularly confronted with situations where the local environment and tissue is insufficient and we must rely on our “biologic tool box.” When the process of bone repair requires additional assistance, we often look to bone grafting to provide an osteoconductive, osteoinductive, and/or osteogenic environment to promote bone healing and repair. The primary workhorses of bone grafting include autogenous bone, cadaver allograft, and bone graft substitutes. Among the first types of bone graft used and still used in large quantities today include autogenous and cadaver allograft bone. Allografts are useful because it is present in multiple forms that conform to the desired situation. But autogenous bone graft is considered the gold standard because it possesses all the fundamental properties to heal bone. However, it has been associated with high rates of donor site morbidity and typically requires an inpatient hospitalization following the procedure only adding to the associated costs. The first bone graft substitute use was calcium sulfate in 1892, and over the past 122 years advancements have achieved improved material properties of calcium sulfate and helped usher in additional bioceramics for bone grafting. Today there are predominantly four types of bioceramics available, which include calcium sulfate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. They come in multiple forms ranging from pellets and solid blocks to injectable and moldable putty. In comparison to autogenous bone graft, the primary limitation of bioceramics are the lack of osteogenic and osteoinductive properties. Bioceramics work by creating an osteoconductive scaffold to promote osteosynthesis. The options of bone graft substitutes don't end with these four types of bioceramics. Composite bioceramics take advantage of the differing biomechanical properties of these four basis types of bioceramics to develop improved materials. To overcome the lack of osteoinductive and osteogenic properties growth factors or bone marrow aspirate can be added to the bioceramic. As a result, the list of combinations available in our “biologic tool box” continues to expand. More than 20 BMPs have been identified, but only BMP-2 and BMP-7 have FDA approval. As we look forward to areas of future research and need within
Bone is a dynamic organ with remarkable regenerative properties seen only otherwise in the liver. However, bone healing requires vascularity, stability, growth factors, a matrix for growth, and viable cells to obtain effective osteosynthesis. We rely on these principles not only to heal fractures, but also achieve healing of benign bone defects. Unfortunately, we are regularly confronted with situations where the local environment and tissue is insufficient and we must rely on our “biologic tool box.” When the process of bone repair requires additional assistance, we often look to bone grafting to provide an osteoconductive, osteoinductive, and/or osteogenic environment to promote bone healing and repair. The primary workhorses of bone grafting includes autogenous bone, cadaver allograft, and bone graft substitutes. Among the first types of bone graft used and still used in large quantities today include autogenous and cadaver allograft bone. Allografts are useful because it is present in multiple forms that conform to the desired situation. But autogenous bone graft is considered the gold standard because it possesses all the fundamental properties to heal bone. However, it has been associated with high rates of donor site morbidity and typically requires an inpatient hospitalization following the procedure only adding to the associated costs. The first bone graft substitute use was calcium sulfate in 1892, and over the past 122 years advancements have achieved improved material properties of calcium sulfate and helped usher in additional bioceramics for bone grafting. Today there are predominantly 4 types of bioceramics available, which include calcium sulfate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. They come in multiple forms ranging from pellets and solid blocks to injectable and moldable putty. In comparison to autogenous bone graft, the primary limitation of bioceramics are the lack of osteogenic and osteoinductive properties. Bioceramics work by creating an osteoconductive scaffold to promote osteosynthesis. The options of bone graft substitutes don't end with these four types of bioceramics. Composite bioceramics take advantage of the differing biomechanical properties of these four basis types of bioceramics to develop improved materials. To overcome the lack of osteoinductive and osteogenic properties growth factors or bone marrow aspirate can be added to the bioceramic. As a result, the list of combinations available in our “biologic tool box” continues to expand. More than 20 BMPs have been identified, but only BMP-2 and BMP-7 have FDA approval. As we look forward to areas of future research and need within
Bone is a dynamic organ with remarkable regenerative properties seen only otherwise in the liver. However, bone healing requires vascularity, stability, growth factors, a matrix for growth, and viable cells to obtain effective osteosynthesis. We rely on these principles not only to heal fractures, but also achieve healing of benign bone defects. Unfortunately we are regularly confronted with situations where the local environment and tissue is insufficient and we must rely on our “biologic tool box.” When the process of bone repair requires additional assistance, we often look to bone grafting to provide an osteoconductive, osteoinductive, and/or osteogenic environment to promote bone healing and repair. The primary workhorses of bone grafting include autogenous bone, cadaver allograft, and bone graft substitutes. Among the first types of bone graft used and still used in large quantities today include autogenous and cadaver allograft bone. Allografts are useful because it is present in multiple forms that conform to the desired situation. But autogenous bone graft is considered the gold standard because it possesses all the fundamental properties to heal bone. However, it has been associated with high rates of donor site morbidity and typically requires an inpatient hospitalization following the procedure only adding to the associated costs. The first bone graft substitute use was calcium sulfate in 1892, and over the past 122 years advancements have achieved improved material properties of calcium sulfate and helped usher in additional bioceramics for bone grafting. Today there are predominantly 4 types of bioceramics available, which include calcium sulfate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. They come in multiple forms ranging from pellets and solid blocks to injectable and moldable putty. In comparison to autogenous bone graft, the primary limitation of bioceramics are the lack of osteogenic and osteoinductive properties. Bioceramics work by creating an osteoconductive scaffold to promote osteosynthesis. The options of bone graft substitutes don't end with these four types of bioceramics. Composite bioceramics take advantage of the differing biomechanical properties of these four basis types of bioceramics to develop improved materials. To overcome the lack of osteoinductive and osteogenic properties growth factors or bone marrow aspirate can be added to the bioceramic. As a result, the list of combinations available in our “biologic tool box” continues to expand. More than 20 BMPs have been identified, but only BMP-2 and BMP-7 have FDA approval. As we look forward to areas of future research and need within
Background. Subtalar nonunion has a detrimental effect on patients' function, and pose a significant challenge for surgeons particularly in the setting of higher risk factors. Methods. We retrospectively analyzed a consecutive series of 49 subtalar nonunions between October 2001 and July 2013. Patient records and radiographs were reviewed for specific patient demographics and comorbidities, subsequent treatments, revision fusion rate, use of bone graft, complications, and clinical outcome. Results. Forty-nine patients with a mean age of 49 years (range 23–80) were included. Sixteen (32%) were heavy smokers (>1 pack per day) and five (10%) had diabetes. Forty one (84%) of the nonunions were symptomatic and underwent a revision procedure at a mean of 16 months (range 2.8 to 57) from the time of the primary arthrodesis. Four of these patients required a triple arthrodesis at the time of revision. Bone graft was used in all cases, and in 25 cases (61%) additional adjuvant
Bone is a dynamic organ with remarkable regenerative properties seen only otherwise in the liver. However, bone healing requires vascularity, stability, growth factors, a matrix for growth, and viable cells to obtain effective osteosynthesis. We rely on these principles not only to heal fractures, but also achieve healing of benign bone defects. Unfortunately, we are regularly confronted with situations where the local environment and tissue is insufficient and we must rely on our “biologic tool box.” When the process of bone repair requires additional assistance, we often look to bone grafting to provide an osteoconductive, osteoinductive, and/or osteogenic environment to promote bone healing and repair. The primary workhorses of bone grafting include autogenous bone, cadaver allograft, and bone graft substitutes. Among the first types of bone graft used and still used in large quantities today include autogenous and cadaver allograft bone. Allografts are useful because they are present in multiple forms that conform to the desired situation. But autogenous bone graft is considered the gold standard because it possesses all the fundamental properties to heal bone. However, it has been associated with high rates of donor site morbidity and typically requires an inpatient hospitalization following the procedure only adding to the associated costs. The first bone graft substitute used was calcium sulfate in 1892, and over the past 122 years advancements have achieved improved material properties of calcium sulfate and helped usher in additional bioceramics for bone grafting. Today there are predominantly four types of bioceramics available, which include calcium sulfate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. They come in multiple forms ranging from pellets and solid blocks to injectable and moldable putty. In comparison to autogenous bone graft, the primary limitation of bioceramics are the lack of osteogenic and osteoinductive properties. Bioceramics work by creating an osteoconductive scaffold to promote osteosynthesis. The options of bone graft substitutes don't end with these four types of bioceramics. Composite bioceramics take advantage of the differing biomechanical properties of these four basis types of bioceramics to develop improved materials. To overcome the lack of osteoinductive and osteogenic properties growth factors or bone marrow aspirate can be added to the bioceramic. As a result, the list of combinations available in our “biologic tool box” continues to expand. More than 20 BMPs have been identified, but only BMP-2 and BMP-7 have FDA approval. As we look forward to areas of future research and need within
Bone is a dynamic organ with remarkable regenerative properties seen only otherwise in the liver. However, bone healing requires vascularity, stability, growth factors, a matrix for growth, and viable cells to obtain effective osteosynthesis. We rely on these principles not only to heal fractures, but also achieve healing of benign bone defects. Unfortunately we are regularly confronted with situations where the local environment and tissue is insufficient and we must rely on our “biologic tool box.” When the process of bone repair requires additional assistance, we often look to bone grafting to provide an osteoconductive, osteoinductive, and/or osteogenic environment to promote bone healing and repair. The primary workhorses of bone grafting includes autogenous bone, cadaver allograft, and bone graft substitutes. Among the first types of bone graft used and still used in large quantities today include autogenous and cadaver allograft bone. Allografts are useful because it is present in multiple forms that conform to the desired situation. But autogenous bone graft is considered the gold standard because it possesses all the fundamental properties to heal bone. However, it has been associated with high rates of donor site morbidity and typically requires an inpatient hospitalization following the procedure only adding to the associated costs. The first bone graft substitute use was calcium sulfate in 1892, and over the past 122 years advancements have achieved improved material properties of calcium sulfate and helped usher in additional bioceramics for bone grafting. Today there are predominantly 4 types of bioceramics available, which include calcium sulfate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. They come in multiple forms ranging from pellets and solid blocks to injectable and moldable putty. In comparison to autogenous bone graft, the primary limitation of bioceramics are the lack of osteogenic and osteoinductive properties. Bioceramics work by creating an osteoconductive scaffold to promote osteosynthesis. The options of bone graft substitutes don't end with these four types of bioceramics. Composite bioceramics take advantage of the differing biomechanical properties of these four basis types of bioceramics to develop improved materials. To overcome the lack of osteoinductive and osteogenic properties growth factors or bone marrow aspirate can be added to the bioceramic. As a result, the list of combinations available in our “biologic tool box” continues to expand. More than 20 BMPs have been identified, but only BMP-2 and BMP-7 have FDA approval. As we look forward to areas of future research and need within
Summary. The BMP-2 content and bone forming potential of 2 leading allograft products (OsteoAMP® and Osteocel® Plus) was tested across 3 commercially available lots. Surprisingly, there was no BMP-2 content associated with the cells contained within Osteocel® Plus. OsteoAMP® contained greater than 1000 times the overall BMP-2 content than Osteocel® Plus. Correspondingly, Osteocel® Plus did not form new bone at any timepoint in the 12 week in vivo study while OsteoAMP® had increasing new bone formation at each sequential timepoint. Interestingly, the highest cellularity of Osteocel® Plus was just prior to implant at t. 0. , decreasing at each timepoint, decreasing further at the terminal endpoint of the study at 12 weeks (82% of cells had died or migrated). Conversely, the cellularity of OsteoAMP® increased at each timepoint. Introduction. Implants containing living cells are often characterised by the
Purpose. Platelet-Rich Plasma (PRP), an autologous derivative of whole blood that contains a supraphysiological concentration of platelets and growth factors. Most published studies have investigated the effect of PRP-conditioned media on cell cultures. We are not aware of any study that has investigated whole PRP with its cellular components on human tissue cultures. This study aims to investigate the effect of PRP on cell migration from human Achilles tendon explants, and the subsequent cellular proliferative effects in culture. Methods. This is an in-vitro study on tendon explants obtained from Achilles tendon rupture patients. The samples were collected in sterile DMEM F12 solution then carefully cut into approximately 1–3mm. 3. sections. Tendon explants were cultured in three media types: 1. 100% PRP; 2. 50% PRP; and 3. 50% fetal calf serum (FCS). 1 and 2 were made up using DMEM F12 media (standard culture medium). Explants and cells were incubated at 37°c in 5% CO. 2. for 48 hours. Results. Images of the explanted tissue were taken using a Nikon TE300 microscope with Retiga CCD camera and cells around each explant were counted. Kruskal-Wallis statistical test showed that 100%PRP and 50%PRP cultured explants have significantly higher number of cells (p ≤0.002 and 0.028 respectively) when compared with 50%FCS cultured explants. Ziva ultrasensitive proliferation assay revealed that 100%PRP significantly increased cell proliferation. In addition, PicoGreen assay showed that DNA content of 100% PRP cultured cells were significantly higher than the control. The concentration of TGF-b1, VEGF, PDGF-AB and IGF-1 growth factors were significantly higher in PRP comparing to 50% FCS medium. Conclusion. Our findings show that whole PRP strongly affect the behaviour of human tenocytes, indicating that PRP may have potential role as an
