Matthias Pumberger

Biomaterials based strategies for skeletal muscle tissue engineering: Existing technologies and future trends

Skeletal muscles have a robust capacity to regenerate, but under compromised conditions, such as severe trauma, the loss of muscle functionality is inevitable. Research carried out in the field of skeletal muscle tissue engineering has elucidated multiple intrinsic mechanisms of skeletal muscle repair, and has thus sought to identify various types of cells and bioactive factors which play an important role during regeneration. In order to maximize the potential therapeutic effects of cells and growth factors, several biomaterial based strategies have been developed and successfully implemented in animal muscle injury models. A suitable biomaterial can be utilized as a template to guide tissue reorganization, as a matrix that provides optimum micro-environmental conditions to cells, as a delivery vehicle to carry bioactive factors which can be released in a controlled manner, and as local niches to orchestrate in situ tissue regeneration. A myriad of biomaterials, varying in geometrical structure, physical form, chemical properties, and biofunctionality have been investigated for skeletal muscle tissue engineering applications. In the current review, we present a detailed summary of studies where the use of biomaterials favorably influenced muscle repair. Biomaterials in the form of porous three-dimensional scaffolds, hydrogels, fibrous meshes, and patterned substrates with defined topographies, have each displayed unique benefits, and are discussed herein. Additionally, several biomaterial based approaches aimed specifically at stimulating vascularization, innervation, and inducing contractility in regenerating muscle tissues are also discussed. Finally, we outline promising future trends in the field of muscle regeneration involving a deeper understanding of the endogenous healing cascades and utilization of this knowledge for the development of multifunctional, hybrid, biomaterials which support and enable muscle regeneration under compromised conditions.

Neurologic deficit following lateral lumbar interbody fusion

PurposeLateral lumbar interbody fusion (LLIF) is a minimally invasive technique that has gained growing interest in recent years. We performed a retrospective review of the medical records and operative reports of patients undergoing LLIF between March 2006 and December 2009. We seek to identify the incidence and nature of neurological deficits following LLIF.MethodsNew occurring sensory and motor deficits were recorded at 6 and 12xa0weeks as well as 6- and 12xa0months of follow-up. Motor deficits were grouped according to the muscle weakness and severity and sensory deficits to the dermatomal zone. New events were correlated to the patient demographics, pre-operative diagnosis, operative levels, and duration of surgery. At each post-operative time-point patients were queried regarding the presence of leg pain.ResultsA total of 235 patients (139 F; 96 M) with a total of 444 levels fused were included. Average age was 61.5 and mean BMI 28.3. At 12xa0months’ follow-up, the prevalence of sensory deficits was 1.6%, psoas mechanical deficit was 1.6% and lumbar plexus related deficits 2.9%. Although there was no significant correlation between the surgical level L4–5 and an increased psoas mechanical flexion or lumbar plexus related motor deficit, a trend was observed. Independent risk factors for both psoas mechanical hip flexion deficit and lumbar plexus related motor deficit was duration of surgery.ConclusionLLIF is a valuable tool for achieving fusion through a minimally invasive approach with little risk to neurovascular structures.

A Stimuli-Responsive Hydrogel for Doxorubicin Delivery

The goal of this study was to develop a polymeric carrier for delivery of anti-tumor drugs and sustained release of these agents in order to optimize anti-tumor activity while minimizing systemic effects. We used oligo(poly(ethylene glycol) fumarate) (OPF) hydrogels modified with small negatively charged molecules, sodium methacrylate (SMA), for delivery of doxorubicin (DOX). SMA at different concentrations was incorporated into the OPF hydrogel with a photo-crosslinking method. The resulting hydrogels exhibited sensitivity to the pH and ionic strength of the surrounding environment. Our results revealed that DOX was bound to the negatively charged hydrogel through electrostatic interaction and was released in a timely fashion with an ion-exchange mechanism. Release kinetics of DOX was directly correlated to the concentration of SMA in the hydrogel formulations. Anti-tumor activity of the released DOX was assessed using a human osteosarcoma cell line. Our data revealed that DOX released from the modified, charged hydrogels remained biologically active and had the capability to kill cancer cells. In contrast, control groups of unmodified OPF hydrogels with or without DOX did not exhibit any cytotoxicity. This study demonstrates the feasibility of using SMA-modified OPF hydrogels as a potential carrier for chemotherapeutic drugs for cancer treatments.

Cervical Radiculopathy: A Review

BackgroundCervical radiculopathy is defined as a syndrome of pain and/or sensorimotor deficits due to compression of a cervical nerve root. Understanding of this disease is vital for rapid diagnosis and treatment of patients with this condition, facilitating their recovery and return to regular activity.PurposeThis review is designed to clarify (1) the pathophysiology that leads to nerve root compression; (2) the diagnosis of the disease guided by history, physical exam, imaging, and electrophysiology; and (3) operative and non-operative options for treatment and how these should be applied.MethodsThe PubMed database was searched for relevant articles and these articles were reviewed by independent authors. The conclusions are presented in this manuscript.ResultsFacet joint spondylosis and herniation of the intervertebral disc are the most common causes of nerve root compression. The clinical consequence of radiculopathy is arm pain or paresthesias in the dermatomal distribution of the affected nerve and may or may not be associated with neck pain and motor weakness. Patient history and clinical examination are important for diagnosis. Further imaging modalities, such as x-ray, computed tomography, magnetic resonance imaging, and electrophysiologic testing, are of importance. Most patients will significantly improve from non-surgical active and passive therapies. Indicated for surgery are patients with clinically significant motor deficits, debilitating pain that is resistant to conservative modalities and/or time, or instability in the setting of disabling radiculopathy. Surgical treatment options include anterior cervical decompression with fusion and posterior cervical laminoforaminotomy.ConclusionUnderstanding the pathophysiology, diagnosis, treatment indications, and treatment techniques is essential for rapid diagnosis and care of patients with cervical radiculopathy.

Degenerative Scoliosis: A Review

Degenerative lumbar scoliosis is a coronal deviation of the spine that is prevalent in the elderly population. Although the etiology is unclear, it is associated with progressive and asymmetric degeneration of the disc, facet joints, and other structural spinal elements typically leading to neural element compression. Clinical presentation varies and is frequently associated with axial back pain and neurogenic claudication. Indications for treatment include pain, neurogenic symptoms, and progressive cosmetic deformity. Non-operative treatment includes physical conditioning and exercise, pharmacological agents for pain control, and use of orthotics and invasive modalities like epidural and facet injections. Operative treatment should be contemplated after multi-factorial and multidisciplinary evaluation of the risks and the benefits. Options include decompression, instrumented stabilization with posterior or anterior fusion, correction of deformity, or a combination of these that are tailored to each patient. Incidence of perioperative complications is substantial and must be considered when deciding appropriate operative treatment. The primary goal of surgical treatment is to provide pain relief and to improve the quality of life with minimum risk of complications.

Metabolic syndrome and lumbar spine fusion surgery: epidemiology and perioperative outcomes.

Study Design. Analysis of the National Inpatient Sample database from 2000 to 2008. Objective. To identify whether metabolic syndrome is an independent risk factor for increased major perioperative complications, cost, length of stay, and nonroutine discharge. Summary of Background Data. Metabolic syndrome is a combination of medical disorders that has been shown to increase the health risk of the general population. No study has analyzed its impact in the perioperative spine surgery setting. Methods. We obtained the National Inpatient Sample from the Hospital Cost and Utilization Project for each year between 2000 and 2008. All patients undergoing primary posterior lumbar spine fusion were identified and separated into groups with and without metabolic syndrome. Patient demographics and health care system–related parameters were compared. The outcomes of major complications, nonroutine discharge, length of hospital stay, and hospitalization charges were assessed for both groups. Regression analysis was performed to identify whether the presence of metabolic syndrome was an independent risk factor for each outcome. Results. An estimated 1,152,747 primary posterior lumbar spine fusions were performed between 2000 and 2008 in the United States. The prevalence of metabolic syndrome as well as the comorbidities of the patients increased significantly over time. Patients with metabolic syndrome had significantly longer length of stay, higher hospital charges, higher rates of nonroutine discharges, and increased rates of major life-threatening complications than patients without metabolic syndrome. Conclusion. Patients with metabolic syndrome undergoing primaryposterior lumbar spinal fusion represent an increasing financial burden on the health care system. Clinicians should recognize that metabolic syndrome represents a risk factor for increased perioperative morbidity.

Degenerative Lumbar Spinal Stenosis: Evaluation and Management

&NA; Degenerative lumbar spinal stenosis is caused by mechanical factors and/or biochemical alterations within the intervertebral disk that lead to disk space collapse, facet joint hypertrophy, soft‐tissue infolding, and osteophyte formation, which narrows the space available for the thecal sac and exiting nerve roots. The clinical consequence of this compression is neurogenic claudication and varying degrees of leg and back pain. Degenerative lumbar spinal stenosis is a major cause of pain and impaired quality of life in the elderly. The natural history of this condition varies; however, it has not been shown to worsen progressively. Nonsurgical management consists of nonsteroidal anti‐inflammatory drugs, physical therapy, and epidural steroid injections. If nonsurgical management is unsuccessful and neurologic decline persists or progresses, surgical treatment, most commonly laminectomy, is indicated. Recent prospective randomized studies have demonstrated that surgery is superior to nonsurgical management in terms of controlling pain and improving function in patients with lumbar spinal stenosis.

National in-hospital morbidity and mortality trends after lumbar fusion surgery between 1998 and 2008

Increasing numbers of posterior lumbar fusions are being performed. The purpose of this study was to identify trends in demographics, mortality and major complications in patients undergoing primary posterior lumbar fusion. We accessed data collected for the Nationwide Inpatient Sample for each year between 1998 and 2008 and analysed trends in the number of lumbar fusions, mean patient age, comorbidity burden, length of hospital stay, discharge status, major peri-operative complications and mortality. An estimated 1xa0288xa0496 primary posterior lumbar fusion operations were performed between 1998 and 2008 in the United States. The total number of procedures, mean patient age and comorbidity burden increased over time. Hospital length of stay decreased, although the in-hospital mortality (adjusted and unadjusted for changes in length of hospital stay) remained stable. However, a significant increase was observed in peri-operative septic, pulmonary and cardiac complications. Although in-hospital mortality rates did not change over time in the setting of increases in mean patient age and comorbidity burden, some major peri-operative complications increased. These trends highlight the need for appropriate peri-operative services to optimise outcomes in an increasingly morbid and older population of patients undergoing lumbar fusion.

Epidemiology and risk factors for perioperative mortality after total hip and knee arthroplasty

The perioperative mortality of total knee and hip arthroplasties (TKA, THA) remains a major concern among health care providers and their patients. The increase in utilization of TKA and THA makes it imperative to be aware of factors that are associated with this unfortunate event. Therefore we analyzed the Nationwide Inpatient Sample data from 1998 to 2008 and compared admissions with perioperative mortality to those that survived their hospitalization. An estimated total of 4,438,213 TKA and 2,182,121 THA procedures were performed in the United States between 1998 and 2008. The average mortality rate for TKA was 0.13% and 0.18% for THA, or 0.34 and 0.44 events per 1,000 inpatient days, respectively. Independent risk factors for in‐hospital mortality were advanced age, male gender, ethnic minority background, emergency admission as well as a number of comorbidities and complications. Furthermore, we demonstrated that the timing of death occurred earlier after TKA when compared to THA, with 50% of fatalities occurring by day 4 versus day 6 of the hospitalization, respectively. This study provides nationally representative information on risk factors for and timing of perioperative mortality after TKA and THA. Our data can be used to assess the risk for perioperative mortality and to develop targeted intervention to decrease such risk.

Perioperative mortality after lumbar spinal fusion surgery: an analysis of epidemiology and risk factors

Study designAnalysis of the Nationwide Inpatient Sample (NIS) from 1998 to 2008.ObjectiveTo analyze the most recent available and nationally representative data for risk factors contributing to in-hospital mortality after primary lumbar spine fusion.Summary of background dataThe total number of lumbar spine fusion surgeries has increased dramatically over the past decades. While the field of spine fusion surgery remains highly dynamic with changes in perioperative care constantly affecting patient care, recent data affecting rates and risk for perioperative mortality remain very limited.MethodsWe obtained the NIS from the Hospital cost and utilization project. The impact of patient and health care system related demographics, including various comorbidities as well as postoperative complications on the outcome of in-hospital mortality after spine fusion were studied. Furthermore, we analyzed the timing of in-hospital mortality.ResultsAn estimated total of 1,288,496 primary posterior lumbar spine fusion procedures were performed in the US between 1998 and 2008. The average mortality rate for lumbar spine fusion surgery was 0.2xa0%. Independent risk factors for in-hospital mortality included advanced age, male gender, large hospital size, and emergency admission. Comorbidities associated with the highest in-hospital mortality after lumbar spine fusion surgery were coagulopathy, metastatic cancer, congestive heart failure and renal disease. Most lethal complications were cerebrovascular events, sepsis and pulmonary embolism. Furthermore, we demonstrated that the timing of death occurred relatively early in the in-hospital period with over half of fatalities occurring by postoperative dayxa09.ConclusionThis study provides nationally representative information on risk factors for and timing of perioperative mortality after primary lumbar spine fusion surgery. These data can be used to assess risk for this event and to develop targeted intervention to decrease such risk.