The exceptional properties of graphene enable applications in electronics, optoelectronics, energy storage, and structural composites. Here we demonstrate a 3D printable graphene (3DG) composite ...consisting of majority graphene and minority polylactide-co-glycolide, a biocompatible elastomer, 3D-printed from a liquid ink. This ink can be utilized under ambient conditions via extrusion-based 3D printing to create graphene structures with features as small as 100 μm composed of as few as two layers (<300 μm thick object) or many hundreds of layers (>10 cm thick object). The resulting 3DG material is mechanically robust and flexible while retaining electrical conductivities greater than 800 S/m, an order of magnitude increase over previously reported 3D-printed carbon materials. In vitro experiments in simple growth medium, in the absence of neurogenic stimuli, reveal that 3DG supports human mesenchymal stem cell (hMSC) adhesion, viability, proliferation, and neurogenic differentiation with significant upregulation of glial and neuronal genes. This coincides with hMSCs adopting highly elongated morphologies with features similar to axons and presynaptic terminals. In vivo experiments indicate that 3DG has promising biocompatibility over the course of at least 30 days. Surgical tests using a human cadaver nerve model also illustrate that 3DG has exceptional handling characteristics and can be intraoperatively manipulated and applied to fine surgical procedures. With this unique set of properties, combined with ease of fabrication, 3DG could be applied toward the design and fabrication of a wide range of functional electronic, biological, and bioelectronic medical and nonmedical devices.
Using an innovative, tissue‐independent approach to decellularized tissue processing and biomaterial fabrication, the development of a series of “tissue papers” derived from native porcine ...tissues/organs (heart, kidney, liver, muscle), native bovine tissue/organ (ovary and uterus), and purified bovine Achilles tendon collagen as a control from decellularized extracellular matrix particle ink suspensions cast into molds is described. Each tissue paper type has distinct microstructural characteristics as well as physical and mechanical properties, is capable of absorbing up to 300% of its own weight in liquid, and remains mechanically robust (E = 1–18 MPa) when hydrated; permitting it to be cut, rolled, folded, and sutured, as needed. In vitro characterization with human mesenchymal stem cells reveals that all tissue paper types support cell adhesion, viability, and proliferation over four weeks. Ovarian tissue papers support mouse ovarian follicle adhesion, viability, and health in vitro, as well as support, and maintain the viability and hormonal function of nonhuman primate and human follicle‐containing, live ovarian cortical tissues ex vivo for eight weeks postmortem. “Tissue papers” can be further augmented with additional synthetic and natural biomaterials, as well as integrated with recently developed, advanced 3D‐printable biomaterials, providing a versatile platform for future multi‐biomaterial construct manufacturing.
This work describes a new, chemical‐independent, comprehensive approach for fabricating tissue‐ and organ‐specific, decellularized matrix‐based biomaterials: “tissue papers” (TPs). TPs are biocompatible, bioactive, surgically friendly, and compatible with existing, new 3D‐printable biomaterials.
To compare targeted muscle reinnervation (TMR) to "standard treatment" of neuroma excision and burying into muscle for postamputation pain.
To date, no intervention is consistently effective for ...neuroma-related residual limb or phantom limb pain (PLP). TMR is a nerve transfer procedure developed for prosthesis control, incidentally found to improve postamputation pain.
A prospective, randomized clinical trial was conducted. 28 amputees with chronic pain were assigned to standard treatment or TMR. Primary outcome was change between pre- and postoperative numerical rating scale (NRS, 0-10) pain scores for residual limb pain and PLP at 1 year. Secondary outcomes included NRS for all patients at final follow-up, PROMIS pain scales, neuroma size, and patient function.
In intention-to-treat analysis, changes in PLP scores at 1 year were 3.2 versus -0.2 (difference 3.4, adjusted confidence interval (aCI) -0.1 to 6.9, adjusted P = 0.06) for TMR and standard treatment, respectively. Changes in residual limb pain scores were 2.9 versus 0.9 (difference 1.9, aCI -0.5 to 4.4, P = 0.15). In longitudinal mixed model analysis, difference in change scores for PLP was significantly greater in the TMR group compared with standard treatment mean (aCI) = 3.5 (0.6, 6.3), P = 0.03. Reduction in residual limb pain was favorable for TMR (P = 0.10). At longest follow-up, including 3 crossover patients, results favored TMR over standard treatment.
In this first surgical RCT for the treatment of postamputation pain in major limb amputees, TMR improved PLP and trended toward improved residual limb pain compared with conventional neurectomy.
NCT02205385 at ClinicalTrials.gov.
A majority of the nearly 2 million Americans living with limb loss suffer from chronic pain in the form of neuroma-related residual limb and phantom limb pain (PLP). Targeted muscle reinnervation ...(TMR) surgically transfers amputated nerves to nearby motor nerves for prevention of neuroma. The objective of this study was to determine whether TMR at the time of major limb amputation decreases the incidence and severity of PLP and residual limb pain.
A multi-institutional cohort study was conducted between 2012 and 2018. Fifty-one patients undergoing major limb amputation with immediate TMR were compared with 438 unselected major limb amputees. Primary outcomes included an 11-point Numerical Rating Scale (NRS) and Patient-Reported Outcomes Measurement Information System (PROMIS) pain intensity, behavior, and interference.
Patients who underwent TMR had less PLP and residual limb pain compared with untreated amputee controls, across all subgroups and by all measures. Median “worst pain in the past 24 hours” for the TMR cohort was 1 out of 10 compared to 5 (PLP) and 4 (residual) out of 10 in the control population (p = 0.003 and p < 0.001, respectively). Median PROMIS t-scores were lower in TMR patients for both PLP (pain intensity 36.3 vs 48.3, pain behavior 50.1 vs 56.6, and pain interference 40.7 vs 55.8) and residual limb pain (pain intensity 30.7 vs 46.8, pain behavior 36.7 vs 57.3, and pain interference 40.7 vs 57.3). Targeted muscle reinnervation was associated with 3.03 (PLP) and 3.92 (residual) times higher odds of decreasing pain severity compared with general amputee participants.
Preemptive surgical intervention of amputated nerves with TMR at the time of limb loss should be strongly considered to reduce pathologic phantom limb pain and symptomatic neuroma-related residual limb pain.
Seroma in Prosthetic Breast Reconstruction Jordan, Sumanas W; Khavanin, Nima; Kim, John Y S
Plastic and reconstructive surgery (1963),
2016-April, Letnik:
137, Številka:
4
Journal Article
Recenzirano
Seroma, as a complication of prosthetic breast reconstruction, results in patient distress, increased office visits, undesirable aesthetic outcomes, and--importantly--may escalate to infection and ...frank prosthesis loss. Herein, the authors review the pathophysiology and risk factors and attempt to collate published practices for avoidance and management of seroma.
A systematic literature review was performed using MEDLINE, Web of Science, Embase, and Cochrane Library for studies published between 2000 and January of 2015. Random-effects meta-analysis was used to estimate the overall pooled incidence of seroma and to examine the effect of drain number and acellular dermal matrix use.
Seventy-two relevant primary articles and three systematic reviews were identified. Fifty-one citations met inclusion criteria, including two randomized controlled trials. The overall pooled incidence was 5.4 percent (95 percent CI, 4.1 to 6.7 percent). Obesity, acellular dermal matrix, and preoperative irradiation were cited risk factors. Pooled relative risk for acellular dermal matrix was 1.83 (95 percent CI, 1.28 to 2.62). Drain practices were collated from 34 articles.
Seromas following prosthetic breast reconstruction are complicated by the hypovascular, proinflammatory milieu of the mastectomy skin flap, the geometrically complex dead space, and the presence of a foreign body with potential contamination and biofilm. There is reasonable evidence to suggest that these factors contribute to a progression of seroma to infection and prosthesis loss. These findings have motivated this summary article on current practice guidelines and strategies to prevent and treat seromas.
Risk, II.
Autologous bone grafts remain the gold standard for craniofacial reconstruction despite limitations of donor-site availability and morbidity. A myriad of commercial bone substitutes and allografts ...are available, yet no product has gained widespread use because of inferior clinical outcomes. The ideal bone substitute is both osteoconductive and osteoinductive. Craniofacial reconstruction often involves irregular three-dimensional defects, which may benefit from malleable or customizable substrates. "Hyperelastic Bone" is a three-dimensionally printed synthetic scaffold, composed of 90% by weight hydroxyapatite and 10% by weight poly(lactic-co-glycolic acid), with inherent bioactivity and porosity to allow for tissue integration. This study examines the capacity of Hyperelastic Bone for bone regeneration in a critical-size calvarial defect.
Eight-millimeter calvarial defects in adult male Sprague-Dawley rats were treated with three-dimensionally printed Hyperelastic Bone, three-dimensionally printed Fluffy-poly(lactic-co-glycolic acid) without hydroxyapatite, autologous bone (positive control), or left untreated (negative control). Animals were euthanized at 8 or 12 weeks postoperatively and specimens were analyzed for new bone formation by cone beam computed tomography, micro-computed tomography, and histology.
The mineralized bone volume-to-total tissue volume fractions for the Hyperelastic Bone cohort at 8 and 12 weeks were 74.2 percent and 64.5 percent of positive control bone volume/total tissue, respectively (p = 0.04). Fluffy-poly(lactic-co-glycolic acid) demonstrated little bone formation, similar to the negative control. Histologic analysis of Hyperelastic Bone scaffolds revealed fibrous tissue at 8 weeks, and new bone formation surrounding the scaffold struts by 12 weeks.
Findings from our study suggest that Hyperelastic Bone grafts are effective for bone regeneration, with significant potential for clinical translation.
Despite substantial attention given to the development of osteoregenerative biomaterials, severe deficiencies remain in current products. These limitations include an inability to adequately, ...rapidly, and reproducibly regenerate new bone; high costs and limited manufacturing capacity; and lack of surgical ease of handling. To address these shortcomings, we generated a new, synthetic osteoregenerative biomaterial, hyperelastic "bone" (HB). HB, which is composed of 90 weight % (wt %) hydroxyapatite and 10 wt % polycaprolactone or poly(lactic-co-glycolic acid), could be rapidly three-dimensionally (3D) printed (up to 275 cm(3)/hour) from room temperature extruded liquid inks. The resulting 3D-printed HB exhibited elastic mechanical properties (~32 to 67% strain to failure, ~4 to 11 MPa elastic modulus), was highly absorbent (50% material porosity), supported cell viability and proliferation, and induced osteogenic differentiation of bone marrow-derived human mesenchymal stem cells cultured in vitro over 4 weeks without any osteo-inducing factors in the medium. We evaluated HB in vivo in a mouse subcutaneous implant model for material biocompatibility (7 and 35 days), in a rat posterolateral spinal fusion model for new bone formation (8 weeks), and in a large, non-human primate calvarial defect case study (4 weeks). HB did not elicit a negative immune response, became vascularized, quickly integrated with surrounding tissues, and rapidly ossified and supported new bone growth without the need for added biological factors.
After reading this article, the participants should be able to: 1. List current nonsurgical and surgical strategies for addressing postamputation neuroma pain and discuss their limitations. 2. ...Summarize the indications and rationale for targeted muscle reinnervation. 3. Develop an operative plan for targeted muscle reinnervation in an acute or delayed fashion for upper and lower extremity amputations. 4. Propose a management algorithm for treatment of symptomatic neuromas in an intact limb. 5. Discuss the risk of neuroma development after primary revision digital amputation or secondary surgery for a digital neuroma. 6. Compare and contrast targeted muscle reinnervation to the historical gold standard neuroma treatment of excision and burying the involved nerve in muscle, bone, or vein graft. 7. Interpret and discuss the evidence that targeted muscle reinnervation improves postamputation neuroma and phantom pain when performed either acutely or in a delayed fashion to treat existing pain.
Symptomatic injured nerves resulting from amputations, extremity trauma, or prior surgery are common and can decrease patient quality of life, thus necessitating an effective strategy for management. Targeted muscle reinnervation is a modern surgical strategy for prevention and treatment of neuroma pain that promotes nerve regeneration and healing rather than neuroma formation. Targeted muscle reinnervation involves the transfer of cut peripheral nerves to small motor nerves of adjacent, newly denervated segments of muscle and can be easily performed without specialized equipment. Targeted muscle reinnervation strategies exist for both upper and lower extremity amputations and for symptomatic neuromas of intact limbs. Targeted muscle reinnervation has been shown in a prospective, randomized, controlled trial to result in lower neuroma and phantom pain when compared to the historical gold standard of burying cut nerves in muscle.
Targeted muscle reinnervation is an emerging surgical technique to treat neuroma pain whereby sensory and mixed motor nerves are transferred to nearby redundant motor nerve branches. In a recent ...randomized controlled trial, targeted muscle reinnervation was recently shown to reduce postamputation pain relative to conventional neuroma excision and muscle burying.
(1) Does targeted muscle reinnervation improve residual limb pain and phantom limb pain in the period before surgery to 1 year after surgery? (2) Does targeted muscle reinnervation improve Patient-reported Outcome Measurement System (PROMIS) pain intensity and pain interference scores at 1 year after surgery? (3) After 1 year, does targeted muscle reinnervation improve functional outcome scores (Orthotics Prosthetics User Survey OPUS with Rasch conversion and Neuro-Quality of Life Neuro-QOL)?
Data on patients who were ineligible for randomization or declined to be randomized and underwent targeted muscle reinnervation for pain were gathered for the present analysis. Data were collected prospectively from 2013 to 2017. Forty-three patients were enrolled in the study, 10 of whom lacked 1-year follow-up, leaving 33 patients for analysis. The primary outcomes measured were the difference in residual limb and phantom limb pain before and 1 year after surgery, assessed by an 11-point numerical rating scale (NRS). Secondary outcomes were change in PROMIS pain measures and change in limb function, assessed by the OPUS Rasch for upper limbs and Neuro-QOL for lower limbs before and 1 year after surgery.
By 1 year after targeted muscle reinnervation, NRS scores for residual limb pain from 6.4 ± 2.6 to 3.6 ± 2.2 (mean difference -2.7 95% CI -4.2 to -1.3; p < 0.001) and phantom limb pain decreased from 6.0 ± 3.1 to 3.6 ± 2.9 (mean difference -2.4 95% CI -3.8 to -0.9; p < 0.001). PROMIS pain intensity and pain interference scores improved with respect to residual limb and phantom limb pain (residual limb pain intensity: 53.4 ± 9.7 to 44.4 ± 7.9, mean difference -9.0 95% CI -14.0 to -4.0; residual limb pain interference: 60.4 ± 9.3 to 51.7 ± 8.2, mean difference -8.7 95% CI -13.1 to -4.4; phantom limb pain intensity: 49.3 ± 10.4 to 43.2 ± 9.3, mean difference -6.1 95% CI -11.3 to -0.9; phantom limb pain interference: 57.7 ± 10.4 to 50.8 ± 9.8, mean difference -6.9 95% CI -12.1 to -1.7; p ≤ 0.012 for all comparisons). On functional assessment, OPUS Rasch scores improved from 53.7 ± 3.4 to 56.4 ± 3.7 (mean difference +2.7 95% CI 2.3 to 3.2; p < 0.001) and Neuro-QOL scores improved from 32.9 ± 1.5 to 35.2 ± 1.6 (mean difference +2.3 95% CI 1.8 to 2.9; p < 0.001).
Targeted muscle reinnervation demonstrates improvement in residual limb and phantom limb pain parameters in major limb amputees. It should be considered as a first-line surgical treatment option for chronic amputation-related pain in patients with major limb amputations. Additional investigation into the effect on function and quality of life should be performed.
Level IV, therapeutic study.
Targeted muscle reinnervation (TMR) is a technique for the management of peripheral nerves in amputation. Phantom limb pain (PLP) and residual limb pain (RLP) trouble many patients after amputation, ...and TMR has been shown to reduce this pain when performed after the initial amputation. We hypothesize that TMR at the time of amputation may improve pain for patients after major upper-extremity amputation.
We conducted a retrospective review of patients who underwent major upper-extremity amputation with TMR performed at the time of the index amputation (early TMR). Phantom limb pain and RLP intensity and associated symptoms were assessed using the numeric rating scale (NRS), the Patient-Reported Outcome Measurement Information System (PROMIS) Pain Intensity Short-Form 3a, the Pain Behavior Short-Form 7a, and the Pain Interference Short-Form 8a. The TMR cohort was compared with benchmarked data from a sample of upper-extremity amputees.
Sixteen patients underwent early TMR and were compared with 55 benchmark patients. More than half of early TMR patients were without PLP (62%) compared with 24% of controls. Furthermore, half of all patients were free of RLP compared with 36% of controls. The median PROMIS PLP intensity score for the general sample was 47 versus 38 in the early TMR sample. Patients who underwent early TMR reported reduced pain behaviors and interference specific to PLP (50 vs 53 and 41 vs 50, respectively). The PROMIS RLP intensity score was lower in patients with early TMR (36 vs 47).
This study demonstrates that early TMR is a promising strategy for treating pain and improving the quality of life in the upper-extremity amputee. Early TMR may preclude the need for additional surgery and represents an important technique for peripheral nerve surgery.
Therapeutic IV.
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