The use of orthobiologics as a novel therapy for the treatment of numerous musculoskeletal disord... more The use of orthobiologics as a novel therapy for the treatment of numerous musculoskeletal disorders has increased considerably over the past decade. Currently, there are multiple alternatives available as suitable treatments; however, the use of autologous blood-derived products such as platelet-rich plasma (PRP), bone marrow aspirate (BMA) and BMA concentrate (BMAC), specifically, is expanding. Although many investigations attempted to demonstrate the effectiveness of these therapies, even with positive results, the literature lacks standardized protocols and overall accuracy in study designs, which leads to variance and difficulty in reproducibility of protocols. The efficacy of PRP for the treatment of cartilage, bone and muscle tissues is well known. Although BMAC has generated optimistic results for the same purposes, its applicability in clinical trials is still relatively recent when compared to PRP. Both products demonstrate the potential to set forth reparative processes, each in their own distinct mechanism. The combination of these biological products has been previously proposed, yet little is known about their synergism. Evidence indicates that growth factor, cytokine, and chemokine profiles seen in both PRP and BMAC vary but are likely to work synergistically to enhance musculoskeletal healing. BMAC products seem to work well without PRP; however, the addition of PRP to BMAC has been shown to act as a rich and natural source of culture medium for stem cells located either peripherally or in the bone marrow itself. Nevertheless, additional variables associated with the use of BMAC and PRP in orthopedics must be further evaluated in order to consolidate the efficacy of this therapeutic strategy.
Background: Owing to a paucity of research on minimally processed orthobiologics, we sought to in... more Background: Owing to a paucity of research on minimally processed orthobiologics, we sought to investigate the efficacy of minimally processed bone marrow aspirate (BMA) and fat graft with a leukocyte-rich, platelet-rich plasma (PRP) intra-articular injection series on pain, function, and global rating of change (GROC) among patients with severe knee osteoarthritis (OA). Methods: Thirty-one adults (23 females and 8 males, mean age 67 years) with clinical and radiographic evidence of knee OA (Kellgren-Lawrence ≥ 3) were included. During the initial visit, patients were examined and administered the patient-specific functional scale (PSFS) and a numerical pain rating scale ranging from 0 to 10. Patients then underwent procedures to obtain 4-6 mL of PRP, a minimally processed 6 mL fat graft, and 10 mL of BMA. Patients returned twice over 6-week intervals for booster PRP injections. At each follow-up (F1 and F2), the GROC questionnaire and prior outcome measures were completed. Results: Patients returned at an average of 41 days for the second PRP (F1) and 90 days from initial visit for the third PRP injection (F2). Friedman Chi Square analysis indicated statistically significant improvements in pain (best and worst) and PSFS from initial to F1 and F2 (P ≤ 0.001). Post hoc Wilcoxon signed-ranks analysis with Bonferroni correction identified improvement from initial to F1 and F2, as well as F1-F2 for pain, PSFS, and GROC (P ≤ 0.013). Effect sizes ranged from r = 0.32 to 0.51. Change, based on established minimum clinically important differences, indicated pain, GROC, and PSFS met thresholds at F2. Conclusion: A minimally processed fat graft with BMA and a series of three PRP injections improved pain and function among individuals with severe knee OA who were previously recalcitrant to conservative care. Although results indicated significant improvement, clinically important change did not occur until F2. A one-arm design is a limitation of this study.
The use of orthobiologics as a novel therapy for the treatment of numerous musculoskeletal disord... more The use of orthobiologics as a novel therapy for the treatment of numerous musculoskeletal disorders has increased considerably over the past decade. Currently, there are multiple alternatives available as suitable treatments; however, the use of autologous blood-derived products such as platelet-rich plasma (PRP), bone marrow aspirate (BMA) and BMA concentrate (BMAC), specifically, is expanding. Although many investigations attempted to demonstrate the effectiveness of these therapies, even with positive results, the literature lacks standardized protocols and overall accuracy in study designs, which leads to variance and difficulty in reproducibility of protocols. The efficacy of PRP for the treatment of cartilage, bone and muscle tissues is well known. Although BMAC has generated optimistic results for the same purposes, its applicability in clinical trials is still relatively recent when compared to PRP. Both products demonstrate the potential to set forth reparative processes, each in their own distinct mechanism. The combination of these biological products has been previously proposed, yet little is known about their synergism. Evidence indicates that growth factor, cytokine, and chemokine profiles seen in both PRP and BMAC vary but are likely to work synergistically to enhance musculoskeletal healing. BMAC products seem to work well without PRP; however, the addition of PRP to BMAC has been shown to act as a rich and natural source of culture medium for stem cells located either peripherally or in the bone marrow itself. Nevertheless, additional variables associated with the use of BMAC and PRP in orthopedics must be further evaluated in order to consolidate the efficacy of this therapeutic strategy.
Musculoskeletal disorders are one of the major health burdens and a leading source of disability ... more Musculoskeletal disorders are one of the major health burdens and a leading source of disability worldwide, affecting both juvenile and elderly populations either as a consequence of ageing or extrinsic factors such as physical injuries. This condition often involves a group of locomotor structures such as the bones, joints and muscles and may therefore cause significant economic and emotional impact. Some pharmacological and non-pharmacological treatments have been considered as potential solutions, however, these alternatives have provided quite limited efficacy due to the short-term effect on pain management and inability to restore damaged tissue. The emergence of novel therapeutic alternatives such as the application of orthobiologics, particularly bone marrow aspirate (BMA) clot, have bestowed medical experts with considerable optimism as evidenced by the significant results found in numerous studies addressed in this manuscript. Although other products have been proposed for the treatment of musculoskeletal injuries, the peculiar interest in BMA, fibrin clot and associated fibrinolytic mechanisms continues to expand. BMA is a rich source of various cellular and molecular components which have demonstrated positive effects on tissue regeneration in many in vitro and in vivo models of musculoskeletal injuries. In addition to being able to undergo self-renewal and differentiation, the hematopoietic and mesenchymal stem cells present in this orthobiologic elicit key immunomodulatory and paracrine roles in inflammatory responses in tissue injury and drive the coagulation cascade towards tissue repair via different mechanisms. Although promising, these complex regenerative mechanisms have not yet been fully elucidated.
Background: Owing to a paucity of research on minimally processed orthobiologics, we sought to in... more Background: Owing to a paucity of research on minimally processed orthobiologics, we sought to investigate the efficacy of minimally processed bone marrow aspirate (BMA) and fat graft with a leukocyte-rich, platelet-rich plasma (PRP) intra-articular injection series on pain, function, and global rating of change (GROC) among patients with severe knee osteoarthritis (OA). Methods: Thirty-one adults (23 females and 8 males, mean age 67 years) with clinical and radiographic evidence of knee OA (Kellgren-Lawrence ≥ 3) were included. During the initial visit, patients were examined and administered the patient-specific functional scale (PSFS) and a numerical pain rating scale ranging from 0 to 10. Patients then underwent procedures to obtain 4-6 mL of PRP, a minimally processed 6 mL fat graft, and 10 mL of BMA. Patients returned twice over 6-week intervals for booster PRP injections. At each follow-up (F1 and F2), the GROC questionnaire and prior outcome measures were completed. Results: Patients returned at an average of 41 days for the second PRP (F1) and 90 days from initial visit for the third PRP injection (F2). Friedman Chi Square analysis indicated statistically significant improvements in pain (best and worst) and PSFS from initial to F1 and F2 (P ≤ 0.001). Post hoc Wilcoxon signed-ranks analysis with Bonferroni correction identified improvement from initial to F1 and F2, as well as F1-F2 for pain, PSFS, and GROC (P ≤ 0.013). Effect sizes ranged from r = 0.32 to 0.51. Change, based on established minimum clinically important differences, indicated pain, GROC, and PSFS met thresholds at F2. Conclusion: A minimally processed fat graft with BMA and a series of three PRP injections improved pain and function among individuals with severe knee OA who were previously recalcitrant to conservative care. Although results indicated significant improvement, clinically important change did not occur until F2. A one-arm design is a limitation of this study.
The Sports Medicine and Rehabilitation Column provides practical information on the role of rehab... more The Sports Medicine and Rehabilitation Column provides practical information on the role of rehabilitation and flexibility on both performance and the modification of injury risk.
Background: Owing to a paucity of research on minimally processed orthobiologics, we sought to in... more Background: Owing to a paucity of research on minimally processed orthobiologics, we sought to investigate the efficacy of minimally processed bone marrow aspirate (BMA) and fat graft with a leukocyte-rich, platelet-rich plasma (PRP) intra-articular injection series on pain, function, and global rating of change (GROC) among patients with severe knee osteoarthritis (OA). Methods: Thirty-one adults (23 females and 8 males, mean age 67 years) with clinical and radiographic evidence of knee OA (Kellgren-Lawrence ≥ 3) were included. During the initial visit, patients were examined and administered the patient-specific functional scale (PSFS) and a numerical pain rating scale ranging from 0 to 10. Patients then underwent procedures to obtain 4-6 mL of PRP, a minimally processed 6 mL fat graft, and 10 mL of BMA. Patients returned twice over 6-week intervals for booster PRP injections. At each follow-up (F1 and F2), the GROC questionnaire and prior outcome measures were completed. Results: Patients returned at an average of 41 days for the second PRP (F1) and 90 days from initial visit for the third PRP injection (F2). Friedman Chi Square analysis indicated statistically significant improvements in pain (best and worst) and PSFS from initial to F1 and F2 (P ≤ 0.001). Post hoc Wilcoxon signed-ranks analysis with Bonferroni correction identified improvement from initial to F1 and F2, as well as F1-F2 for pain, PSFS, and GROC (P ≤ 0.013). Effect sizes ranged from r = 0.32 to 0.51. Change, based on established minimum clinically important differences, indicated pain, GROC, and PSFS met thresholds at F2. Conclusion: A minimally processed fat graft with BMA and a series of three PRP injections improved pain and function among individuals with severe knee OA who were previously recalcitrant to conservative care. Although results indicated significant improvement, clinically important change did not occur until F2. A one-arm design is a limitation of this study.
The aim of this paper is to consider the practicalities of using platelet-rich plasma (PRP) and s... more The aim of this paper is to consider the practicalities of using platelet-rich plasma (PRP) and stem cells to treat musculoskeletal conditions in the office setting. The science behind PRP and stem cells, treatment protocols, and contraindications are all discussed.
Platelet- and fibrin-rich orthobiologic products, such as autologous platelet concentrates, have ... more Platelet- and fibrin-rich orthobiologic products, such as autologous platelet concentrates, have been extensively studied and appreciated for their beneficial effects on multiple conditions. Platelet-rich plasma (PRP) and its derivatives, including platelet-rich fibrin (PRF), have demonstrated encouraging outcomes in clinical and laboratory settings, particularly in the treatment of musculoskeletal disorders such as osteoarthritis (OA). Although PRP and PRF have distinct characteristics, they share similar properties. The relative abundance of platelets, peripheral blood cells, and molecular components in these orthobiologic products stimulates numerous biological pathways. These include inflammatory modulation, augmented neovascularization, and the delivery of pro-anabolic stimuli that regulate cell recruitment, proliferation, and differentiation. Furthermore, the fibrinolytic system, which is sometimes overlooked, plays a crucial role in musculoskeletal regenerative medicine by re...
Platelet and fibrin-rich orthobiologic products, such as autologous platelet concentrates, have b... more Platelet and fibrin-rich orthobiologic products, such as autologous platelet concentrates, have been extensively studied and appreciated for their beneficial effects in multiple conditions. PRP and its derivatives, including PRF, have demonstrated encouraging outcomes in clinical and laboratory settings, particularly in the treatment of musculoskeletal disorders such as OA. Although PRP and PRF have distinct characteristics, they share similar properties. The relative abundance of platelets, peripheral blood cells and molecular components in these orthobiologic products stimulate numerous biological pathways. These include inflammatory modulation, augmented neovascularization, and delivery of pro-anabolic stimuli that regulate cell recruitment, proliferation, and differentiation. Furthermore, the fibrinolytic system, which is sometimes overlooked, plays a crucial role in musculoskeletal regenerative medicine by regulating proteolytic activity and promoting the recruitment of inflamm...
Purpose: This study was conducted to investigate the efficacy of a combined minimally processed b... more Purpose: This study was conducted to investigate the efficacy of a combined minimally processed bone marrow aspirate (BMA), adipose graft, and leukocyte-rich platelet-rich plasma (PRP) intra-articular injection series on pain, function, and global rating of change (GROC) among patients with glenohumeral osteoarthritis (GHOA) and record any complications or adverse events associated with the protocol. Methods: Ten adults (mean age 65 years) previously recalcitrant to conservative care with clinical and radiographic evidence of GHOA were included. At the initial visit, patients were assessed for eligibility of treatment. All patients were assessed pre- and post-treatment with numerical pain rating and patient-specific functional scales (PSFS). All study participants were treated with 4–6 ml of PRP, 6 ml adipose graft, and 12 ml of BMA, which were administered via a landmark-based anterior intra-articular injection. Patients were requested to return twice over 4-week intervals for boos...
Journal of Tissue Science and Engineering, Aug 26, 2015
Lipogems a game changer in the field of regenerative stem cell therapy T he use of adipose tissue... more Lipogems a game changer in the field of regenerative stem cell therapy T he use of adipose tissue has taken on increasing importance in the field of regenerative stem cell therapy. This therapy can be divided into two major pathways. One pathway involves plastic and reconstruction surgery. The other major pathway involves orthopedics and its related fields. Other uses are being found in gynecology, urology, and general surgery. Until recently the main uses of adipose tissue centered around the use of enzymatic produced SVF suspensions. Typically these suspensions were made with the use of the enzyme collagenase. Although collagenase has worked well in the past there is now a complaint method of producing a fast, enzyme free lipoaspirate that is turned into a therapeutic product. This new method comes from the Lipogems company. The Lipogems technique has been utilized in over 5,000 patients. It has recently obtained FDA clearance. Lipogems makes use of the high stem cell density of adipose tissue thought to be 1 out of every 100 cells. Lipogems utilizes mild mechanical forces in a closed system to produce micro fractured and purified adipose tissue graft which is non expanded and ready to use in a variety of regenerative applications. More importantly, Lipogems adipose product has a very well preserved vascular stroma with slit-like capillaries wedged between adipo-cytes and vascular channels. The stem cell niche is preserved enabling the pericytes to have a much higher survivability rate. The intact niche provides a perfect environment for reparative response of activated MSCs. As Dr. A. Caplan has pointed out, pericytes are precursor mesenchymal stem cells. Activated MSCs are crucial for the immune modulation and regeneration. The lipoaspirate of Lipogems shows a higher percentage of mature pericytes and hMSCs than enzymatically digested lipoaspirates. We are now aware that there are novel growth factors secreted by Lipogems lipoaspirate which may explain the therapeutic efficacy of Lipogems. Also important, is the fact that the Lipogems technique may preserve the important MUSE cell. Muse cells are unique in that they be pluripotent, have a high survivability rate, and are quite small by stem cell standards. They are considered to be an embryonic like stem cell without any of the risks of regular embryonic stem cells since they are the patient's own. They may represent a quantum leap in regenerative medicine. Since Lipogems preserves these cells it too is a quantum leap.
Background: Owing to a paucity of research on minimally processed orthobiologics, we sought to in... more Background: Owing to a paucity of research on minimally processed orthobiologics, we sought to investigate the efficacy of minimally processed bone marrow aspirate (BMA) and fat graft with a leukocyte-rich, platelet-rich plasma (PRP) intra-articular injection series on pain, function, and global rating of change (GROC) among patients with severe knee osteoarthritis (OA). Methods: Thirty-one adults (23 females and 8 males, mean age 67 years) with clinical and radiographic evidence of knee OA (Kellgren-Lawrence ≥ 3) were included. During the initial visit, patients were examined and administered the patient-specific functional scale (PSFS) and a numerical pain rating scale ranging from 0 to 10. Patients then underwent procedures to obtain 4-6 mL of PRP, a minimally processed 6 mL fat graft, and 10 mL of BMA. Patients returned twice over 6-week intervals for booster PRP injections. At each follow-up (F1 and F2), the GROC questionnaire and prior outcome measures were completed. Results: Patients returned at an average of 41 days for the second PRP (F1) and 90 days from initial visit for the third PRP injection (F2). Friedman Chi Square analysis indicated statistically significant improvements in pain (best and worst) and PSFS from initial to F1 and F2 (P ≤ 0.001). Post hoc Wilcoxon signed-ranks analysis with Bonferroni correction identified improvement from initial to F1 and F2, as well as F1-F2 for pain, PSFS, and GROC (P ≤ 0.013). Effect sizes ranged from r = 0.32 to 0.51. Change, based on established minimum clinically important differences, indicated pain, GROC, and PSFS met thresholds at F2. Conclusion: A minimally processed fat graft with BMA and a series of three PRP injections improved pain and function among individuals with severe knee OA who were previously recalcitrant to conservative care. Although results indicated significant improvement, clinically important change did not occur until F2. A one-arm design is a limitation of this study.
One in four adults in the US suffer from cartilage degeneration of the Intervertebral Disc (DDD) ... more One in four adults in the US suffer from cartilage degeneration of the Intervertebral Disc (DDD) or load bearing joints (DJD). Combined DDD and DJD leads to billions of dollars in surgical health care costs annually. Since cartilage is avascular, it has a limited regenerative capacity. Conventional non-surgical treatment modalities provide brief symptomatic relief, have sided effects, and do not address the actual structural tissue defect in the cartilage itself. As such, new alternatives are needed. Perinatal tissue allografts have emerged as a novel frontier for bio-mechanical cartilage engineering research. Birth product-specific therapeutic roles and clinical outcomes are actively being investigated. The tissues of interest include umbilical cord-derived Wharton’s Jelly (WJ). This study assessed WJ tissue samples via ZEISS Supra 55VP Field-Emission Scanning Electron Microscope (SEM) at 100 and 300nm resolution scales. The captured images of pre and post-processed structural tiss...
We studied the effect of ionizing radiation (IR) on continuous growth of seven hESC lines. Cells ... more We studied the effect of ionizing radiation (IR) on continuous growth of seven hESC lines. Cells were exposed to 0, 0.2, or 1 Gy of X-rays, and the growth rates of cell populations were assessed by measuring areas of the same individual colonies versus time. The population doubling times (DT) of sham-irradiated cells varied from 18.9 to 28.7 hours for different cell lines. All cell lines showed similar reaction to IR, i.e. cell populations dropped within 24-48 hours post IR; after that they recovered and grew with the same rate as the sham-irradiated cells. The relative cell survival (RCS), i.e. the ratio of normalized cell population in the irradiated samples to that of the sham-irradiated ones varied from 0.6 to 0.8 after 0.2 Gy, and from 0.1 to 0.2 after 1 Gy IR for different cell lines. We found that the RCS values of hESC lines correlated directly with their DT, i.e. the faster cells grow the more radiosensitive they are. We also found that DT and RCS values of individual colonies varied significantly within all hESC lines. We believe that the method developed herein can be useful for assessing other cytotoxic insults on cultures of hESC.
Use of centrifuged bone marrow aspirate for regenerative medicine is a growing practice. However,... more Use of centrifuged bone marrow aspirate for regenerative medicine is a growing practice. However, such centrifugation systems require aspirating large volumes (30-240 mL) in order to obtain sufficient stem/progenitor cellularity in a large enough post-centrifugation final volume for therapeutic administration. Presented here are the results of a series of 27 marrow aspirations using Marrow CellutionTM (www.marrowcellution.com), a bone marrow access and retrieval device designed to increase the stem/progenitor cell concentrations from the aspirate. The samples were collected under field conditions from eight separate clinicians using three different independent laboratories. The quality of the marrow aspirate was determined by performing a CFU-f test to determine the number of osteo progenitor cells. Stem cells capable of forming a CFU-f are routinely found in marrow but rarely in peripheral blood. Consequently, CFU-f represents the standard test to determine the number of immature s...
The use of orthobiologics as a novel therapy for the treatment of numerous musculoskeletal disord... more The use of orthobiologics as a novel therapy for the treatment of numerous musculoskeletal disorders has increased considerably over the past decade. Currently, there are multiple alternatives available as suitable treatments; however, the use of autologous blood-derived products such as platelet-rich plasma (PRP), bone marrow aspirate (BMA) and BMA concentrate (BMAC), specifically, is expanding. Although many investigations attempted to demonstrate the effectiveness of these therapies, even with positive results, the literature lacks standardized protocols and overall accuracy in study designs, which leads to variance and difficulty in reproducibility of protocols. The efficacy of PRP for the treatment of cartilage, bone and muscle tissues is well known. Although BMAC has generated optimistic results for the same purposes, its applicability in clinical trials is still relatively recent when compared to PRP. Both products demonstrate the potential to set forth reparative processes, each in their own distinct mechanism. The combination of these biological products has been previously proposed, yet little is known about their synergism. Evidence indicates that growth factor, cytokine, and chemokine profiles seen in both PRP and BMAC vary but are likely to work synergistically to enhance musculoskeletal healing. BMAC products seem to work well without PRP; however, the addition of PRP to BMAC has been shown to act as a rich and natural source of culture medium for stem cells located either peripherally or in the bone marrow itself. Nevertheless, additional variables associated with the use of BMAC and PRP in orthopedics must be further evaluated in order to consolidate the efficacy of this therapeutic strategy.
Background: Owing to a paucity of research on minimally processed orthobiologics, we sought to in... more Background: Owing to a paucity of research on minimally processed orthobiologics, we sought to investigate the efficacy of minimally processed bone marrow aspirate (BMA) and fat graft with a leukocyte-rich, platelet-rich plasma (PRP) intra-articular injection series on pain, function, and global rating of change (GROC) among patients with severe knee osteoarthritis (OA). Methods: Thirty-one adults (23 females and 8 males, mean age 67 years) with clinical and radiographic evidence of knee OA (Kellgren-Lawrence ≥ 3) were included. During the initial visit, patients were examined and administered the patient-specific functional scale (PSFS) and a numerical pain rating scale ranging from 0 to 10. Patients then underwent procedures to obtain 4-6 mL of PRP, a minimally processed 6 mL fat graft, and 10 mL of BMA. Patients returned twice over 6-week intervals for booster PRP injections. At each follow-up (F1 and F2), the GROC questionnaire and prior outcome measures were completed. Results: Patients returned at an average of 41 days for the second PRP (F1) and 90 days from initial visit for the third PRP injection (F2). Friedman Chi Square analysis indicated statistically significant improvements in pain (best and worst) and PSFS from initial to F1 and F2 (P ≤ 0.001). Post hoc Wilcoxon signed-ranks analysis with Bonferroni correction identified improvement from initial to F1 and F2, as well as F1-F2 for pain, PSFS, and GROC (P ≤ 0.013). Effect sizes ranged from r = 0.32 to 0.51. Change, based on established minimum clinically important differences, indicated pain, GROC, and PSFS met thresholds at F2. Conclusion: A minimally processed fat graft with BMA and a series of three PRP injections improved pain and function among individuals with severe knee OA who were previously recalcitrant to conservative care. Although results indicated significant improvement, clinically important change did not occur until F2. A one-arm design is a limitation of this study.
The use of orthobiologics as a novel therapy for the treatment of numerous musculoskeletal disord... more The use of orthobiologics as a novel therapy for the treatment of numerous musculoskeletal disorders has increased considerably over the past decade. Currently, there are multiple alternatives available as suitable treatments; however, the use of autologous blood-derived products such as platelet-rich plasma (PRP), bone marrow aspirate (BMA) and BMA concentrate (BMAC), specifically, is expanding. Although many investigations attempted to demonstrate the effectiveness of these therapies, even with positive results, the literature lacks standardized protocols and overall accuracy in study designs, which leads to variance and difficulty in reproducibility of protocols. The efficacy of PRP for the treatment of cartilage, bone and muscle tissues is well known. Although BMAC has generated optimistic results for the same purposes, its applicability in clinical trials is still relatively recent when compared to PRP. Both products demonstrate the potential to set forth reparative processes, each in their own distinct mechanism. The combination of these biological products has been previously proposed, yet little is known about their synergism. Evidence indicates that growth factor, cytokine, and chemokine profiles seen in both PRP and BMAC vary but are likely to work synergistically to enhance musculoskeletal healing. BMAC products seem to work well without PRP; however, the addition of PRP to BMAC has been shown to act as a rich and natural source of culture medium for stem cells located either peripherally or in the bone marrow itself. Nevertheless, additional variables associated with the use of BMAC and PRP in orthopedics must be further evaluated in order to consolidate the efficacy of this therapeutic strategy.
Musculoskeletal disorders are one of the major health burdens and a leading source of disability ... more Musculoskeletal disorders are one of the major health burdens and a leading source of disability worldwide, affecting both juvenile and elderly populations either as a consequence of ageing or extrinsic factors such as physical injuries. This condition often involves a group of locomotor structures such as the bones, joints and muscles and may therefore cause significant economic and emotional impact. Some pharmacological and non-pharmacological treatments have been considered as potential solutions, however, these alternatives have provided quite limited efficacy due to the short-term effect on pain management and inability to restore damaged tissue. The emergence of novel therapeutic alternatives such as the application of orthobiologics, particularly bone marrow aspirate (BMA) clot, have bestowed medical experts with considerable optimism as evidenced by the significant results found in numerous studies addressed in this manuscript. Although other products have been proposed for the treatment of musculoskeletal injuries, the peculiar interest in BMA, fibrin clot and associated fibrinolytic mechanisms continues to expand. BMA is a rich source of various cellular and molecular components which have demonstrated positive effects on tissue regeneration in many in vitro and in vivo models of musculoskeletal injuries. In addition to being able to undergo self-renewal and differentiation, the hematopoietic and mesenchymal stem cells present in this orthobiologic elicit key immunomodulatory and paracrine roles in inflammatory responses in tissue injury and drive the coagulation cascade towards tissue repair via different mechanisms. Although promising, these complex regenerative mechanisms have not yet been fully elucidated.
Background: Owing to a paucity of research on minimally processed orthobiologics, we sought to in... more Background: Owing to a paucity of research on minimally processed orthobiologics, we sought to investigate the efficacy of minimally processed bone marrow aspirate (BMA) and fat graft with a leukocyte-rich, platelet-rich plasma (PRP) intra-articular injection series on pain, function, and global rating of change (GROC) among patients with severe knee osteoarthritis (OA). Methods: Thirty-one adults (23 females and 8 males, mean age 67 years) with clinical and radiographic evidence of knee OA (Kellgren-Lawrence ≥ 3) were included. During the initial visit, patients were examined and administered the patient-specific functional scale (PSFS) and a numerical pain rating scale ranging from 0 to 10. Patients then underwent procedures to obtain 4-6 mL of PRP, a minimally processed 6 mL fat graft, and 10 mL of BMA. Patients returned twice over 6-week intervals for booster PRP injections. At each follow-up (F1 and F2), the GROC questionnaire and prior outcome measures were completed. Results: Patients returned at an average of 41 days for the second PRP (F1) and 90 days from initial visit for the third PRP injection (F2). Friedman Chi Square analysis indicated statistically significant improvements in pain (best and worst) and PSFS from initial to F1 and F2 (P ≤ 0.001). Post hoc Wilcoxon signed-ranks analysis with Bonferroni correction identified improvement from initial to F1 and F2, as well as F1-F2 for pain, PSFS, and GROC (P ≤ 0.013). Effect sizes ranged from r = 0.32 to 0.51. Change, based on established minimum clinically important differences, indicated pain, GROC, and PSFS met thresholds at F2. Conclusion: A minimally processed fat graft with BMA and a series of three PRP injections improved pain and function among individuals with severe knee OA who were previously recalcitrant to conservative care. Although results indicated significant improvement, clinically important change did not occur until F2. A one-arm design is a limitation of this study.
The Sports Medicine and Rehabilitation Column provides practical information on the role of rehab... more The Sports Medicine and Rehabilitation Column provides practical information on the role of rehabilitation and flexibility on both performance and the modification of injury risk.
Background: Owing to a paucity of research on minimally processed orthobiologics, we sought to in... more Background: Owing to a paucity of research on minimally processed orthobiologics, we sought to investigate the efficacy of minimally processed bone marrow aspirate (BMA) and fat graft with a leukocyte-rich, platelet-rich plasma (PRP) intra-articular injection series on pain, function, and global rating of change (GROC) among patients with severe knee osteoarthritis (OA). Methods: Thirty-one adults (23 females and 8 males, mean age 67 years) with clinical and radiographic evidence of knee OA (Kellgren-Lawrence ≥ 3) were included. During the initial visit, patients were examined and administered the patient-specific functional scale (PSFS) and a numerical pain rating scale ranging from 0 to 10. Patients then underwent procedures to obtain 4-6 mL of PRP, a minimally processed 6 mL fat graft, and 10 mL of BMA. Patients returned twice over 6-week intervals for booster PRP injections. At each follow-up (F1 and F2), the GROC questionnaire and prior outcome measures were completed. Results: Patients returned at an average of 41 days for the second PRP (F1) and 90 days from initial visit for the third PRP injection (F2). Friedman Chi Square analysis indicated statistically significant improvements in pain (best and worst) and PSFS from initial to F1 and F2 (P ≤ 0.001). Post hoc Wilcoxon signed-ranks analysis with Bonferroni correction identified improvement from initial to F1 and F2, as well as F1-F2 for pain, PSFS, and GROC (P ≤ 0.013). Effect sizes ranged from r = 0.32 to 0.51. Change, based on established minimum clinically important differences, indicated pain, GROC, and PSFS met thresholds at F2. Conclusion: A minimally processed fat graft with BMA and a series of three PRP injections improved pain and function among individuals with severe knee OA who were previously recalcitrant to conservative care. Although results indicated significant improvement, clinically important change did not occur until F2. A one-arm design is a limitation of this study.
The aim of this paper is to consider the practicalities of using platelet-rich plasma (PRP) and s... more The aim of this paper is to consider the practicalities of using platelet-rich plasma (PRP) and stem cells to treat musculoskeletal conditions in the office setting. The science behind PRP and stem cells, treatment protocols, and contraindications are all discussed.
Platelet- and fibrin-rich orthobiologic products, such as autologous platelet concentrates, have ... more Platelet- and fibrin-rich orthobiologic products, such as autologous platelet concentrates, have been extensively studied and appreciated for their beneficial effects on multiple conditions. Platelet-rich plasma (PRP) and its derivatives, including platelet-rich fibrin (PRF), have demonstrated encouraging outcomes in clinical and laboratory settings, particularly in the treatment of musculoskeletal disorders such as osteoarthritis (OA). Although PRP and PRF have distinct characteristics, they share similar properties. The relative abundance of platelets, peripheral blood cells, and molecular components in these orthobiologic products stimulates numerous biological pathways. These include inflammatory modulation, augmented neovascularization, and the delivery of pro-anabolic stimuli that regulate cell recruitment, proliferation, and differentiation. Furthermore, the fibrinolytic system, which is sometimes overlooked, plays a crucial role in musculoskeletal regenerative medicine by re...
Platelet and fibrin-rich orthobiologic products, such as autologous platelet concentrates, have b... more Platelet and fibrin-rich orthobiologic products, such as autologous platelet concentrates, have been extensively studied and appreciated for their beneficial effects in multiple conditions. PRP and its derivatives, including PRF, have demonstrated encouraging outcomes in clinical and laboratory settings, particularly in the treatment of musculoskeletal disorders such as OA. Although PRP and PRF have distinct characteristics, they share similar properties. The relative abundance of platelets, peripheral blood cells and molecular components in these orthobiologic products stimulate numerous biological pathways. These include inflammatory modulation, augmented neovascularization, and delivery of pro-anabolic stimuli that regulate cell recruitment, proliferation, and differentiation. Furthermore, the fibrinolytic system, which is sometimes overlooked, plays a crucial role in musculoskeletal regenerative medicine by regulating proteolytic activity and promoting the recruitment of inflamm...
Purpose: This study was conducted to investigate the efficacy of a combined minimally processed b... more Purpose: This study was conducted to investigate the efficacy of a combined minimally processed bone marrow aspirate (BMA), adipose graft, and leukocyte-rich platelet-rich plasma (PRP) intra-articular injection series on pain, function, and global rating of change (GROC) among patients with glenohumeral osteoarthritis (GHOA) and record any complications or adverse events associated with the protocol. Methods: Ten adults (mean age 65 years) previously recalcitrant to conservative care with clinical and radiographic evidence of GHOA were included. At the initial visit, patients were assessed for eligibility of treatment. All patients were assessed pre- and post-treatment with numerical pain rating and patient-specific functional scales (PSFS). All study participants were treated with 4–6 ml of PRP, 6 ml adipose graft, and 12 ml of BMA, which were administered via a landmark-based anterior intra-articular injection. Patients were requested to return twice over 4-week intervals for boos...
Journal of Tissue Science and Engineering, Aug 26, 2015
Lipogems a game changer in the field of regenerative stem cell therapy T he use of adipose tissue... more Lipogems a game changer in the field of regenerative stem cell therapy T he use of adipose tissue has taken on increasing importance in the field of regenerative stem cell therapy. This therapy can be divided into two major pathways. One pathway involves plastic and reconstruction surgery. The other major pathway involves orthopedics and its related fields. Other uses are being found in gynecology, urology, and general surgery. Until recently the main uses of adipose tissue centered around the use of enzymatic produced SVF suspensions. Typically these suspensions were made with the use of the enzyme collagenase. Although collagenase has worked well in the past there is now a complaint method of producing a fast, enzyme free lipoaspirate that is turned into a therapeutic product. This new method comes from the Lipogems company. The Lipogems technique has been utilized in over 5,000 patients. It has recently obtained FDA clearance. Lipogems makes use of the high stem cell density of adipose tissue thought to be 1 out of every 100 cells. Lipogems utilizes mild mechanical forces in a closed system to produce micro fractured and purified adipose tissue graft which is non expanded and ready to use in a variety of regenerative applications. More importantly, Lipogems adipose product has a very well preserved vascular stroma with slit-like capillaries wedged between adipo-cytes and vascular channels. The stem cell niche is preserved enabling the pericytes to have a much higher survivability rate. The intact niche provides a perfect environment for reparative response of activated MSCs. As Dr. A. Caplan has pointed out, pericytes are precursor mesenchymal stem cells. Activated MSCs are crucial for the immune modulation and regeneration. The lipoaspirate of Lipogems shows a higher percentage of mature pericytes and hMSCs than enzymatically digested lipoaspirates. We are now aware that there are novel growth factors secreted by Lipogems lipoaspirate which may explain the therapeutic efficacy of Lipogems. Also important, is the fact that the Lipogems technique may preserve the important MUSE cell. Muse cells are unique in that they be pluripotent, have a high survivability rate, and are quite small by stem cell standards. They are considered to be an embryonic like stem cell without any of the risks of regular embryonic stem cells since they are the patient's own. They may represent a quantum leap in regenerative medicine. Since Lipogems preserves these cells it too is a quantum leap.
Background: Owing to a paucity of research on minimally processed orthobiologics, we sought to in... more Background: Owing to a paucity of research on minimally processed orthobiologics, we sought to investigate the efficacy of minimally processed bone marrow aspirate (BMA) and fat graft with a leukocyte-rich, platelet-rich plasma (PRP) intra-articular injection series on pain, function, and global rating of change (GROC) among patients with severe knee osteoarthritis (OA). Methods: Thirty-one adults (23 females and 8 males, mean age 67 years) with clinical and radiographic evidence of knee OA (Kellgren-Lawrence ≥ 3) were included. During the initial visit, patients were examined and administered the patient-specific functional scale (PSFS) and a numerical pain rating scale ranging from 0 to 10. Patients then underwent procedures to obtain 4-6 mL of PRP, a minimally processed 6 mL fat graft, and 10 mL of BMA. Patients returned twice over 6-week intervals for booster PRP injections. At each follow-up (F1 and F2), the GROC questionnaire and prior outcome measures were completed. Results: Patients returned at an average of 41 days for the second PRP (F1) and 90 days from initial visit for the third PRP injection (F2). Friedman Chi Square analysis indicated statistically significant improvements in pain (best and worst) and PSFS from initial to F1 and F2 (P ≤ 0.001). Post hoc Wilcoxon signed-ranks analysis with Bonferroni correction identified improvement from initial to F1 and F2, as well as F1-F2 for pain, PSFS, and GROC (P ≤ 0.013). Effect sizes ranged from r = 0.32 to 0.51. Change, based on established minimum clinically important differences, indicated pain, GROC, and PSFS met thresholds at F2. Conclusion: A minimally processed fat graft with BMA and a series of three PRP injections improved pain and function among individuals with severe knee OA who were previously recalcitrant to conservative care. Although results indicated significant improvement, clinically important change did not occur until F2. A one-arm design is a limitation of this study.
One in four adults in the US suffer from cartilage degeneration of the Intervertebral Disc (DDD) ... more One in four adults in the US suffer from cartilage degeneration of the Intervertebral Disc (DDD) or load bearing joints (DJD). Combined DDD and DJD leads to billions of dollars in surgical health care costs annually. Since cartilage is avascular, it has a limited regenerative capacity. Conventional non-surgical treatment modalities provide brief symptomatic relief, have sided effects, and do not address the actual structural tissue defect in the cartilage itself. As such, new alternatives are needed. Perinatal tissue allografts have emerged as a novel frontier for bio-mechanical cartilage engineering research. Birth product-specific therapeutic roles and clinical outcomes are actively being investigated. The tissues of interest include umbilical cord-derived Wharton’s Jelly (WJ). This study assessed WJ tissue samples via ZEISS Supra 55VP Field-Emission Scanning Electron Microscope (SEM) at 100 and 300nm resolution scales. The captured images of pre and post-processed structural tiss...
We studied the effect of ionizing radiation (IR) on continuous growth of seven hESC lines. Cells ... more We studied the effect of ionizing radiation (IR) on continuous growth of seven hESC lines. Cells were exposed to 0, 0.2, or 1 Gy of X-rays, and the growth rates of cell populations were assessed by measuring areas of the same individual colonies versus time. The population doubling times (DT) of sham-irradiated cells varied from 18.9 to 28.7 hours for different cell lines. All cell lines showed similar reaction to IR, i.e. cell populations dropped within 24-48 hours post IR; after that they recovered and grew with the same rate as the sham-irradiated cells. The relative cell survival (RCS), i.e. the ratio of normalized cell population in the irradiated samples to that of the sham-irradiated ones varied from 0.6 to 0.8 after 0.2 Gy, and from 0.1 to 0.2 after 1 Gy IR for different cell lines. We found that the RCS values of hESC lines correlated directly with their DT, i.e. the faster cells grow the more radiosensitive they are. We also found that DT and RCS values of individual colonies varied significantly within all hESC lines. We believe that the method developed herein can be useful for assessing other cytotoxic insults on cultures of hESC.
Use of centrifuged bone marrow aspirate for regenerative medicine is a growing practice. However,... more Use of centrifuged bone marrow aspirate for regenerative medicine is a growing practice. However, such centrifugation systems require aspirating large volumes (30-240 mL) in order to obtain sufficient stem/progenitor cellularity in a large enough post-centrifugation final volume for therapeutic administration. Presented here are the results of a series of 27 marrow aspirations using Marrow CellutionTM (www.marrowcellution.com), a bone marrow access and retrieval device designed to increase the stem/progenitor cell concentrations from the aspirate. The samples were collected under field conditions from eight separate clinicians using three different independent laboratories. The quality of the marrow aspirate was determined by performing a CFU-f test to determine the number of osteo progenitor cells. Stem cells capable of forming a CFU-f are routinely found in marrow but rarely in peripheral blood. Consequently, CFU-f represents the standard test to determine the number of immature s...
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