Peripheral Nerve Repair and Reconstruction Griffin, Justin W; Hogan, MaCalus V; Chhabra, A Bobby ...
Journal of bone and joint surgery. American volume,
2013-December-4, Letnik:
95, Številka:
23
Journal Article
Recenzirano
➤ When possible, direct repair remains the current standard of care for the repair of peripheral nerve lacerations.➤ In large nerve gaps, in which direct repair is not possible, grafting remains the ...most viable option.➤ Nerve scaffolds include autologous conduits, artificial nonbioabsorbable conduits, and bioabsorbable conduits and are options for repair of digital nerve gaps that are <3 cm in length.➤ Experimental studies suggest that the use of allografts may be an option for repairing larger sensory nerve gaps without associated donor-site morbidity.
Platelet-rich plasma (PRP) is widely used to treat tendon injuries in clinics. These PRP preparations often contain white blood cells or leukocytes, and the precise cellular effects of leukocyte-rich ...PRP (L-PRP) on tendons are not well defined. Therefore, in this study, we determined the effects of L-PRP on tendon stem/progenitor cells (TSCs), which play a key role in tendon homeostasis and repair.
TSCs isolated from the patellar tendons of rabbits were treated with L-PRP or P-PRP (pure PRP without leukocytes) in vitro, followed by measuring cell proliferation, stem cell marker expression, inflammatory gene expression, and anabolic and catabolic protein expression by using immunostaining, quantitative real-time polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay, respectively.
Cell proliferation was induced by both L-PRP and P-PRP in a dose-dependent manner with maximum proliferation at a 10 % PRP dose. Both PRP treatments also induced differentiation of TSCs into active tenocytes. Nevertheless, the two types of PRP largely differed in several effects exerted on TSCs. L-PRP induced predominantly catabolic and inflammatory changes in differentiated tenocytes; its treatment increased the expression of catabolic marker genes, matrix metalloproteinase-1 (MMP-1), MMP-13, interleukin-1beta (IL-1β), IL-6 and tumor necrosis factor-alpha (TNF-α), and their respective protein expression and prostaglandin E2 (PGE 2) production. In contrast, P-PRP mainly induced anabolic changes; that is, P-PRP increased the gene expression of anabolic genes, alpha-smooth muscle actin (α-SMA), collagen types I and III.
These findings indicate that, while both L-PRP and P-PRP appear to be "safe" in inducing TSC differentiation into active tenocytes, L-PRP may be detrimental to the healing of injured tendons because it induces catabolic and inflammatory effects on tendon cells and may prolong the effects in healing tendons. On the other hand, when P-PRP is used to treat acutely injured tendons, it may result in the formation of excessive scar tissue due to the strong potential of P-PRP to induce inordinate cellular anabolic effects.
Platelet-rich plasma (PRP) is a widely used autologous treatment for tendon injuries in clinics. Platelets (PLTs) are a major source of high mobility group box1 (HMGB1) that is gaining attention as a ...chemoattractant that can recruit stem cells to the wound area to enhance healing of injured tissues; however, the contribution of PLT HMGB1 in wounded tendon healing remains unexplored. This study investigated the effect of PLT HMGB1 within PRP on tendon healing using PLT HMGB1 knockout (KO) and GFP mice. A window defect was created in the patellar tendons of both groups of mice, and wounds were treated with either saline, PRP isolated from PLT HMGB1-KO mice, or PRP isolated from GFP mice. Seven days post-treatment, animals were sacrificed and analyzed by gross inspection, histology, and immunostaining for characteristic signs of tendon healing and repair. Our results showed that in comparison to mice treated with PRP from PLT HMGB1-KO mice, wounds treated with PRP from GFP mice healed faster and exhibited a better organization in tendon structure. Mice treated with PRP from PLT HMGB1-KO mice produced tendon tissue with large premature wound areas and low cell densities. However, wounds of PLT HMGB1-KO mice showed better healing with PRP from HMGB1-KO mice compared to saline treatment. Moreover, wounds treated with PRP from GFP mice had increased extracellular HMGB1, decreased CD68, increased stem cell markers CD146 and CD73, and increased collagen III protein expression levels compared to those treated with PRP from PLT HMGB1-KO mice. Thus, PLT HMGB1 within PRP plays an important role in tendon wound healing by decreasing inflammation, increasing local HMGB1 levels, and recruiting stem cells to the wound area in the tendon. Our findings also suggest that the efficacy of PRP treatment for tendon injuries in clinics may depend on PLT HMGB1 within PRP preparations.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Ligamentous ankle injuries are the most common injuries sustained by athletes and by the general population, with an incidence of approximately 2 million per year in the U.S. Injuries to the ankle ...syndesmosis (i.e., "high ankle sprains") are generally treated operatively. Although cadaveric studies can evaluate syndesmosis fixation strength, they cannot predict how healing, neuromuscular adaptation, or dynamic loading will affect in vivo biomechanics. Using dynamic biplane radiography (DBR), we tested the hypothesis that syndesmosis repair would restore ankle kinematics and ligament elongation during static and dynamic loading.
A convenience sample of 6 male patients who had undergone fixation (2 screw, 3 suspensory, 1 hybrid) of syndesmosis injury were assessed with use of DBR during forward running, backpedaling, a 45° angled single-leg hop, and 1 static standing trial at 2 to 4.5 years postoperatively. Three-dimensional ankle kinematics and elongation of the distal interosseous ligament, anterior inferior tibiofibular ligament, and the posterior inferior tibiofibular ligament were measured bilaterally. Comparisons were made between the operative and uninjured sides. Clinical outcomes were evaluated with use of the Foot and Ankle Ability Measure.
Static load increased the lengths of the distal interosseous ligament (p = 0.02 to 0.05) and middle segment of the anterior inferior tibiofibular ligament (p = 0.02) in the operative ankle. The distal syndesmosis length was greater on the operative side during the static unloaded and loaded conditions (p = 0.02). Length of the distal syndesmosis on the operative side was greater than the corresponding healthy syndesmosis length during all 3 dynamic activities. On average, the operative ankle was in less dorsiflexion over the support phase of the angled hop (p = 0.05) and running (p < 0.01). The average Foot and Ankle Ability Measure Activities of Daily Living and Sports subscale scores were 95 and 88, respectively.
This study provides the first in vivo evidence of post-fixation changes in biomechanics after syndesmosis repair. Syndesmosis repair fails to restore healthy static and dynamic distal tibiofibular anatomy, even in patients who report good to excellent clinical outcomes.
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
➤ Despite being a social construct, race has an impact on outcomes in musculoskeletal spine care.➤ Race is associated with other social determinants of health that may predispose patients to worse ...outcomes.➤ The musculoskeletal spine literature is limited in its understanding of the causes of race-related outcome trends.➤ Efforts to mitigate race-related disparities in spine care require individual, institutional, and national initiatives.
The aims of this study were to compare male versus female and dominant versus non-dominant kinematics in the ankle and hindfoot, and to characterize coupled motion between the subtalar and tibiotalar ...joints during the support phase of gait. Twenty healthy adults walked on a laboratory walkway while synchronized biplane radiographs of the ankle and hindfoot were collected at 100 frames/s. A validated tracking technique was used to measure tibiotalar and subtalar kinematics. Differences between male and female range of motion (ROM) were observed only in tibiotalar (AP and ML) and subtalar (ML) translation (all differences<1 mm and all p < 0.04). Statistical parametric mapping identified differences between kinematics waveforms of males and females in tibiotalar translation (AP and ML) and eversion, and subtalar ML translation. No differences between dominant and non-dominant sides were observed in ROM or kinematics waveforms. The average absolute side-to-side difference in the kinematics waveforms was 4.1° and 1.5 mm or less for all rotations and translations, respectively. Tibiotalar plantarflexion was coupled to subtalar inversion and eversion during the impact and push-off phases of stance (r = 0.90 and r = 0.87, respectively). This data may serve as a guide for evaluating ankle kinematics waveforms, ROM, symmetry, and restoration of healthy coupled motion after surgical intervention or rehabilitation. The observed kinematics differences between males and females may predispose females to higher rates of ankle and knee injury and suggest sex-dependent ankle reconstruction techniques may be beneficial.
The formation of fibrous tissue during the healing of skeletal muscle injuries leads to incomplete recovery of the injured muscle. Platelet-rich-plasma (PRP) contains beneficial growth factors for ...skeletal muscle repair; however, it also contains deleterious cytokines and growth factors, such as TGF- beta 1, that can cause fibrosis and inhibit optimal muscle healing. Objective To test if neutralizing TGF- beta 1's action within PRP, through neutralization antibodies, could improve PRP's beneficial effect on skeletal muscle repair. Methods PRP was isolated from in-bred Fisher rats. TGF- beta 1 neutralization antibody (Ab) was used to block the TGF- beta 1 within the PRP prior to injection. The effects of customized PRP (TGF- beta 1 neutralized PRP) on muscle healing was tested on a cardiotoxin (CTX) induced muscle injury model. Results A significant increase in the numbers of regenerative myofibers was observed in the PRP and customized PRP groups compared to the untreated control. A significant decrease in collagen deposition was observed in customized PRP groups when compared to the control and PRP groups. Significantly enhanced angiogenesis and more Pax-7 positive satellite cells were found in the PRP and customized PRP groups compared to the control group. Macrophage infiltration was increased in the customized PRP groups when compared with the PRP group. More M2 macrophages were recruited to the injury site in the customized PRP groups when compared with the PRP and control groups. Conclusion Neutralizing TGF- beta 1 within PRP significantly promotes muscle regeneration while significantly reducing fibrosis. Not only did the neutralization reduce fibrosis, it enhanced angiogenesis, prolonged satellite cell activation, and recruited a greater number of M2 macrophages to the injury site which also contributed to the efficacy that the customized PRP had on muscle healing.
Abstract The formation of fibrous tissue during the healing of skeletal muscle injuries leads to incomplete recovery of the injured muscle. Platelet-rich-plasma (PRP) contains beneficial growth ...factors for skeletal muscle repair; however, it also contains deleterious cytokines and growth factors, such as TGF-β1, that can cause fibrosis and inhibit optimal muscle healing. Objective To test if neutralizing TGF-β1's action within PRP, through neutralization antibodies, could improve PRP's beneficial effect on skeletal muscle repair. Methods PRP was isolated from in-bred Fisher rats. TGF-β1 neutralization antibody (Ab) was used to block the TGF-β1 within the PRP prior to injection. The effects of customized PRP (TGF-β1 neutralized PRP) on muscle healing was tested on a cardiotoxin (CTX) induced muscle injury model. Results A significant increase in the numbers of regenerative myofibers was observed in the PRP and customized PRP groups compared to the untreated control. A significant decrease in collagen deposition was observed in customized PRP groups when compared to the control and PRP groups. Significantly enhanced angiogenesis and more Pax-7 positive satellite cells were found in the PRP and customized PRP groups compared to the control group. Macrophage infiltration was increased in the customized PRP groups when compared with the PRP group. More M2 macrophages were recruited to the injury site in the customized PRP groups when compared with the PRP and control groups. Conclusion Neutralizing TGF-β1 within PRP significantly promotes muscle regeneration while significantly reducing fibrosis. Not only did the neutralization reduce fibrosis, it enhanced angiogenesis, prolonged satellite cell activation, and recruited a greater number of M2 macrophages to the injury site which also contributed to the efficacy that the customized PRP had on muscle healing.
To examine the differential mechanobiological responses of specific resident tendon cells, we developed an in vivo model of whole-body irradiation followed by injection of either tendon ...stem/progenitor cells (TSCs) expressing green fluorescent protein (GFP-TSCs) or mature tenocytes expressing GFP (GFP-TNCs) into the patellar tendons of wild type C57 mice. Injected mice were subjected to short term (3 weeks) treadmill running, specifically moderate treadmill running (MTR) and intensive treadmill running (ITR). In MTR mice, both GFP-TSC and GFP-TNC injected tendons maintained normal cell morphology with elevated expression of tendon related markers collagen I and tenomodulin. In ITR mice injected with GFP-TNCs, cells also maintained an elongated shape similar to the shape found in normal/untreated control mice, as well as elevated expression of tendon related markers. However, ITR mice injected with GFP-TSCs showed abnormal changes, such as cell morphology transitioning to a round shape, elevated chondrogenic differentiation, and increased gene expression of non-tenocyte related genes LPL, Runx-2, and SOX-9. Increased gene expression data was supported by immunostaining showing elevated expression of SOX-9, Runx-2, and PPARγ. This study provides evidence that while MTR maintains tendon homeostasis by promoting the differentiation of TSCs into TNCs, ITR causes the onset of tendinopathy development by inducing non-tenocyte differentiation of TSCs, which may eventually lead to the formation of non-tendinous tissues in tendon tissue after long term mechanical overloading conditions on the tendon.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Improving the performance and impact of orthopaedic research is a critical leadership challenge. Musculoskeletal (MSK) conditions are a leading cause of disability worldwide, for which research ...investment and performance lags far behind the burden of disease. In the United States, MSK disorders account for the highest health care costs, have increased in incidence at the fastest rate, and exceed the combined costs of cardiovascular diseases and neoplasms. Despite the cost to society, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), with primary responsibility for MSK research, receives <1.4% of the funds allocated to the National Institutes of Health (NIH). Although orthopaedic surgeons are leading providers of MSK clinical care, the dearth of orthopaedic clinician-scientists also greatly reduces representation of MSK scientific and clinical expertise among academic and scientific leaders. The goals of this symposium were to highlight the critical need for greater prioritization and investment in orthopaedic research and to engage orthopaedic leaders in addressing these needs. Compelling stories of research success from 3 orthopaedic chairs were featured to highlight how orthopaedic surgeon leadership in bench-to-bedside research substantially advances MSK clinical care. Seminar participants also emphasized the need to improve evidence-based clinical practice for which multicenter prospective cohort and registry studies represent opportunities for broader involvement. Prioritization of orthopaedic clinician-scientist development and formation of multidisciplinary partnerships with basic and translational scientists were emphasized as critical needs to advance MSK health. It is critical for orthopaedic chairs to "be invested in" and to "invest in" the success of orthopaedic research. This investment includes developing a professional climate that values research achievement and collaboration as well as implementing strategies to support and sustain research success. Finally, orthopaedic leaders need to advocate for federal research funding to be proportional to the economic burden of disease for which MSK conditions carry the highest current and projected costs. With health-care costs accounting for nearly one-fifth of the U.S. economy, increasing the investment in orthopaedic research to reduce the prevalence, disability, and morbidity from MSK disease needs to be a top orthopaedic and national leadership priority.
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