Bone defects can result from different incidents such as acute trauma, infection or tumor resection. While in most instances bone healing can be achieved given the tissue's innate ability of self-repair, for critical-sized defects spontaneous regeneration is less likely to occur, therefore requiring surgical intervention. Current clinical procedures have failed to adequately address this issue. For this reason, bone tissue engineering (BTE) strategies involving the use of synthetic grafts for replacing damaged bone and promoting the tissue's regeneration are being investigated. The electrical stimulation (ES) of bone defects using direct current has yielded very promising results, with neo tissue formation being achieved in the target sites in vivo. Electroactive implantable scaffolds comprised by conductive biomaterials could be used to assist this kind of therapy by either directing the ES specifically to the damaged site or promoting the integration of electrodes within the bone tissue as a coating. In this study, we developed novel conductive heat-treated polyacrylonitrile/poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PAN/PEDOT:PSS) nanofibers via electrospinning capable of mimicking key native features of the bone tissue's extracellular matrix (ECM) and providing a platform for the delivery of exogenous ES. The developed scaffolds were doped with sulfuric acid and mineralized in Simulated Body Fluid to mimic the inorganic phase of bone ECM. As expected, the doped PAN/PEDOT:PSS nanofibers exhibited electroconductive properties and were able to preserve their fibrous structure. The addition of PEDOT:PSS was found to improve the bioactivity of the scaffolds, with a more significant in vitro mineralization being obtained. By seeding the scaffolds with MG-63 osteoblasts and human mesenchymal stem/stromal cells, an increased cell proliferation was observed for the mineralized PAN/PEDOT:PSS nanofibers, which also registered an increased expression of key osteogenic markers (e.g Osteopontin). Our findings appear to corroborate the promising potential of the generated nanofibers for future ES-based BTE applications. Acknowledgements: The authors thank FCT for funding through the projects InSilico4OCReg (PTDC/EME-SIS/0838/2021), BioMaterARISES (EXPL/CTM-CTM/0995/2021) and OptiBioScaffold (PTDC/EME-SIS/32554/2017, POCI-01- 0145-FEDER- 32554), the PhD scholarship (2022.10572.BD) and through institutional funding to iBB (UIDB/04565/2020 and UIDP/04565/2020), Associate Laboratory i4HB (LA/P/0140/2020) and IT (UIDB/50008/2020)

The growing number of non-union fractures in an aging population has increased the clinical demand for tissue-engineered bone. Electrical stimulation (ES) has been described as a promising strategy for bone regeneration treatments in several clinical studies. However the underlying mechanism by which ES augments bone formation is still poorly understood and its use in bone tissue engineering (BTE) strategies is currently underexplored. Additive manufacturing (AM) technologies (Fused Deposition Modeling/3D Printing) have been widely used in BTE due to their ability to fabricate scaffolds with a high control over their structural and mechanical properties in a reproducible and scalable manner. Thus, in this work, we combined AM methods with conductive biomaterials and ES to enhance the osteogenic differentiation of human bone marrow-derived mesenchymal stem/stromal cells (hBMSCs) envisaging improved BTE strategies. First, we started by developing AM-based electro-bioreactor devices containing medical-grade electrodes (stainless steel and Ti6Al4V) to apply ES to monolayer 2D cultures and 3D cell-seeded scaffolds. Computer modeling(Finite Element Analysis-FEA) was employed to predict the magnitude/distribution of electrical fields within the ES devices and along the different conductive scaffolds. Prior to scaffold culture, 5 different ES protocols were tested in terms of their ability to promote hBMSCs proliferation and osteogenic differentiation in 2D cultures. The best performance ES protocol was then used in two different AM-based BTE strategies: 1) Two different conductive scaffolds (conductive poly lactic acid (PLA) and titanium) were seeded with hBMSCs and cultured for 21 days under osteogenic medium conditions with and without ES and their biological performance was evaluated in comparison to non-conductive standard PLA scaffolds; 2) Different PEDOT:PSS-based coating solutions were screened to obtain PEDOT:PSS/Gelatin-coated 3D polycaprolactone (PCL) scaffolds with a high(11 S.cm. -1. ) and stable electroconductivity. When cultured under ES, PEDOT:PSS/Gelatin-PCL scaffolds enhanced significantly hBMSCs osteogenic differentiation and mineralization(calcium deposition), highlighting their potential for BTE applications. Acknowledgements: Funding received from FCT through projects InSilico4OCReg (PTDC/EME-SIS/0838/2021), OptiBioScaffold (PTDC/EME-SIS/4446/2020) and BioMaterARISES (EXPL/CTM-CTM/0995/2021), and to the institutions iBB (UIDB/04565/2020), CDRSP (UIDB/04044/2020) and Associate Laboratory i4HB (LA/P/0140/2020)

Aims

Multiple secondary surgical procedures of the shoulder, such as soft-tissue releases, tendon transfers, and osteotomies, are described in brachial plexus birth palsy (BPBP) patients. The long-term functional outcomes of these procedures described in the literature are inconclusive. We aimed to analyze the literature looking for a consensus on treatment options.

Abstract. Source of Study: London, United Kingdom. This intervention study was conducted to assess two developing protocols for quadriceps and hamstring rehabilitation: Blood Flow Restriction (BFR) and Neuromuscular Electrical Stimulation Training (NMES). BFR involves the application of an external compression cuff to the proximal thigh. In NMES training a portable electrical stimulation unit is connected to the limb via 4 electrodes. In both training modalities, following device application, a standardised set of exercises were performed by all participants. BFR and NMES have been developed to assist with rehabilitation following lower limb trauma and surgery. They offer an alternative for individuals who are unable to tolerate the high mechanical stresses associated with traditional rehabilitation programmes. The use of BFR and NMES in this study was compared across a total of 20 participants. Following allocation into one of the training programmes, the individuals completed training programmes across a 4-week period. Post-intervention outcomes were assessed using Surface Electromyography (EMG) which recorded EMG amplitude values for the following muscles: Vastus Medialis, Vastus Lateralis, Rectus Femoris and Semitendinosus. Increased Semitendinosus muscle activation was observed post intervention in both BFR and NMES training groups. Statistically significant differences between the two groups was not identified. Larger scale randomised-controlled trials are recommended to further assess for possible treatment effects in these promising training modalities

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain.

Cite this article: Bone Joint Res 2022;11(7):439–452.

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review.

Aims

This study aimed to use intraoperative free electromyography to examine how the placement of a retractor at different positions along the anterior acetabular wall may affect the femoral nerve during total hip arthroplasty (THA) when undertaken using the direct anterior approach (THA-DAA).

Several electrical fields are known to be present in bone tissue as originally described by Fukada and Yasuda in the year 1957. Intrinsic voltages can derive from bone deformation and reversely lead to mechanical modifications, called the piezoelectric effect. This effect is used in the clinic for the treatment of bone defects by applying electric and magnetic stimulation directly to the bone supplied with an implant such as the electroinductive screw system. Through this system a sinusoidal alternating voltage with a maximum of 700 mV can be applied which leads to an electric field of 5–70 V/m in the surrounding bone. This approach is established for bone healing therapies. Despite the established clinical application of electrical stimulation in bone, the fundamental processes acting during this stimulation are still poorly understood. A better understanding of the influence of electric fields on cells involved in bone formation is important to improve therapy and clinical success. To study the impact of electrical fields on bone cells in vitro, Ti6Al4V electrodes were designed according to the pattern of the ASNIS III s screw for a 6-well system. Osteoblasts were seeded on collagen coated coverslip and placed centred on the bottom of each well. During four weeks the cells were stimulated 3×45 min/d and metabolic and alkaline phosphatase (ALP) activity as well as gene expression of cells were analysed. Furthermore, supernatants were collected and proteins typical for bone remodelling were examined. The electrical stimulation did not exert a significant influence on the metabolic activity and the ALP production in cells over time using these settings. Gene expression of BSP and ALP was upregulated after the first 3 days whereas OPG was increased in the second half after 14 days of electrical stimulation. Moreover, the concentration of the released proteins OPG, IL-6, DKK-1 and OPN increased when cells were cultivated under electrical stimulation. However, no changes could be seen for essential markers, like RANKL, Leptin, BMP-2, IL-1beta and TNF-alpha. Therefore, further studies will be done with osteoblasts and osteoclasts to study bone remodelling processes under the influence of electrical fields more in detail. This study was supported by the German Research Foundation (DFG) JO 1483/1-1

Aims

The aim of this study was to investigate the efficacy of coccygectomy in patients with persistent coccydynia and coccygeal instability.

In osteoporosis treatment, current interventions, including pharmaceutical treatments and exercise protocols, suffer from challenges of guaranteed efficacy for patients and poor patient compliance. Moreover, bone loss continues to be a complicating factor for conditions such as spinal cord injury, prescribed bed-rest, and space flight. A low-cost treatment modality could improve patient compliance. Electrical stimulation has been shown to improve bone mass in animal models of disuse, but there have been no studies of the effects of electrical stimulation on bone in the context of bone loss under hormone deficiency such as in post-menopausal osteoporosis. The purpose of this study was to explore the effects of electrical stimulation on changes in bone mass in the ovariectomized rat model of post-menopausal osteoporosis. All animal protocols were approved by the institutional Animal Research Ethics Board. We developed a custom electrical stimulation device capable of delivering a constant current, 15 Hz sinusoidal signal. We used 30 female Sprague Dawley rats (12–13 weeks old). Half (n=15) were ovariectomized (OVX), and half (n=15) underwent sham OVX surgery (SHAM). Three of each OVX and SHAM animals were sacrificed at baseline. The remaining 24 rats were separated into four equal groups (n=6 per group): OVX electrical stimulation (OVX-stim), OVX no stimulation (OVX-no stim), SHAM electrical stimulation (SHAM-stim), and SHAM no stimulation (SHAM-no stim). While anaesthetized, stimulation groups received transdermal electrical stimulation to the right knee through bilateral skin-mounted electrodes (10 × 10 mm) with electrode gel. The left knee served as a non-stimulated contralateral control. The no-stimulation groups had electrodes placed on the right knee, but not connected. Rats underwent the stim/no-stim procedure for one hour per day for six weeks. Rats were sacrificed (CO2) after six weeks. Femurs and tibias were scanned by microCT focussed on the proximal tibia and distal femur. MicroCT data were analyzed for trabecular bone measures of bone volume fraction (BV/TV), thickness (Tb.Th), and anisotropy, and cortical bone cross-sectional area and second moment of area. Femurs and tibias from OVX rats had significantly less trabecular bone than SHAM (femur BV/TV = −74.1%, tibia BV/TV = −77.6%). In the distal femur of OVX-stim rats, BV/TV was significantly greater in the stimulated right (11.4%, p < 0 .05) than the non-stimulated contralateral (left). BV/TV in the OVX-stim right femur also tended to be greater than that in the OVX-no-stim right femur, but the difference was not significant (17.7%, p=0.22). There were no differences between stim and no-stim groups for tibial trabecular measures, or cortical bone measures in either the femur or the tibia. This study presents novel findings that electrical stimulation can partially mitigate bone loss in the OVX rat femur, a model of human post-menopausal bone loss. Further work is needed to explore why there was a differential response of the tibial and femoral bone, and to better understand how bone cells respond to electrical stimulation. The long-term goal of this work is to determine if electrical stimulation could be used as a complementary modality for preventing post-menopausal bone loss

Bone is one of the most highly adaptive tissues in the body, possessing the capability to alter its morphology and function in response to stimuli in its surrounding environment. The ability of bone to sense and convert external mechanical stimuli into a biochemical response, which ultimately alters the phenotype and function of the cell, is described as mechanotransduction. This review aims to describe the fundamental physiology and biomechanisms that occur to induce osteogenic adaptation of a cell following application of a physical stimulus. Considerable developments have been made in recent years in our understanding of how cells orchestrate this complex interplay of processes, and have become the focus of research in osteogenesis. We will discuss current areas of preclinical and clinical research exploring the harnessing of mechanotransductive properties of cells and applying them therapeutically, both in the context of fracture healing and de novo bone formation in situations such as nonunion.

Cite this article: Bone Joint Res 2019;9(1):1–14.

Purposes of the study and background. An increasing number of clinical studies involving a range of chronic pain conditions report widespread mechanical pressure pain hypersensitivity, which is commonly interpreted as resulting from central sensitization (CS). Secondary hyperalgesia (increased pinprick sensitivity surrounding the site of injury) is considered to be a manifestation of central sensitization. However, it has not been rigorously tested whether central sensitization induced by peripheral nociceptive input, involves widespread mechanical pressure pain hypersensitivity. The aim of this study was to assess whether high frequency electrical stimulation (HFS), which induces a robust secondary hyperalgesia, also induces a widespread decrease of pain pressure thresholds (PPTs). Summary of the methods and results. We measured PPTs bilaterally on the temples (temporalis muscles), on the legs (tibialis anterior muscles) and on the ventral forearm (flexor carpi radialis muscles) before, 20 min after, and 45 min after applying HFS on the ventral forearm of sixteen healthy young volunteers. To evaluate the presence of secondary hyperalgesia, mechanical pin-prick sensitivity was assessed on the skin surrounding the site where HFS was applied and also on the contralateral arm. HFS induced a significant increase in mechanical pinprick sensitivity on the HFS-treated arm. However, HFS did not decrease PPTs either in the area of increased pinprick sensitivity nor at more distant sites. Conclusion. The present study provides no evidence for the hypothesis that central sensitization, induced after intense activation of skin nociceptors, involves a widespread decrease of PPTs. No conflicts of interest. Sources of Funding: This study was funded by the Université Catholique de Louvain

Aims

The aims of this study were to assess the exposure and preservation of the abductor mechanism during primary total hip arthroplasty (THA) using the posterior approach, and to evaluate gluteus maximus transfer to restore abductor function of chronically avulsed gluteus medius and minimus.

Complete or nearly complete disruption of the attachment of the gluteus is seen in 10–20% of cases at the time of THA. Special attention is needed to identify the lesion at the time of surgery because the avulsion often is visible only after a thickened hypertrophic trochanteric bursa is removed. From 1/1/09 to 12/31/13, 525 primary hip replacements were performed by a single surgeon. After all total hip components were implanted, the greater trochanteric bursa was removed, and the gluteus medius and minimus attachments to the greater trochanter were visualised and palpated. Ninety-five hips (95 patients) were found to have damage to the muscle attachments to bone. Fifty-four hips had mild damage consisting of splits in the tendon, but no frank avulsion of abductor tendon from their bone attachments. None of these cases had severe atrophy of the abductor muscles, but all had partial fatty infiltration. All hips with this mild lesion had repair of the tendons with #5 Ticron sutures to repair the tendon bundles together, and drill holes through bone to anchor the repair to the greater trochanter. Forty-one hips had severe damage with complete or nearly complete avulsion of the gluteus medius and minimus muscles from their attachments to the greater trochanter. Thirty-five of these hips had partial fatty infiltration of the abductor muscles, but all responded to electrical stimulation. The surface of the greater trochanter was denuded of soft tissue with a rongeur, the muscles were repaired with five-seven #5 Ticron mattress sutures passed through drill holes in the greater trochanter, and a gluteus maximus flap was transferred to the posterior third of the greater trochanter and sutured under the vastus lateralis. Six hips had complete detachment of the gluteus medius and minimus muscles, severe atrophy of the muscles, and poor response of the muscles to electrical stimulation. The gluteus medius and minimus muscles were sutured to the greater trochanter, and gluteus maximus flap was transferred as in the group with functioning gluteus medius and minimus muscles. Postoperatively, patients were instructed to protect the hip for 8 weeks, then abductor exercises were started. The normal hips all had negative Trendelenburg tests at 2 and 5 years postoperative with mild lateral hip pain reported by 11 patients at 2 years, and 12 patients at 5 years. In the group of 54 with mild abductor tendon damage that were treated with simple repair, positive Trendelenburg test was found in 5 hips at 2 years and in 8 hips at 5 years. Lateral hip pain was reported in 7 hips at 2 years, and in 22 at 5 years. In the group of 35 hips with severe avulsion but good muscle tissue, who underwent repair with gluteus maximus flap transfer, all had good abduction against gravity and negative Trendelenburg tests at 2 and 5 years postoperative, and none had lateral hip pain. Of the 6 hips with complete avulsion and poor muscle who underwent abductor muscle repair and gluteus maximus flap transfer, all had weak abduction against gravity, mildly positive Trendelenburg sign, and mild lateral hip pain at 2 and 5 years postoperative. Abductor avulsion is uncommon but not rare, and is detected during THA only by direct examination of the tendon and removal of the trochanteric bursa. Simple repair of mild abductor tendon damage did not prevent progressive abductor weakness in some hips; and the increase in number of patients with lateral hip pain from 2 to 5 years suggests progressive deterioration. Augmentation of the repair with a gluteus maximus flap appears to provide a stable reconstruction of the abductor muscles, and seemed to restore abductor function in the hips with functioning muscles

Abstract

Nerve transfer has become a common and often effective reconstructive strategy for proximal and complex peripheral nerve injuries of the upper limb. This case-based discussion explores the principles and potential benefits of nerve transfer surgery and offers in-depth discussion of several established and valuable techniques including: motor transfer for elbow flexion after musculocutaneous nerve injury, deltoid reanimation for axillary nerve palsy, intrinsic re-innervation following proximal ulnar nerve repair, and critical sensory recovery despite non-reconstructable median nerve lesions.

One of the latest trends in the field of tissue engineering is the development of in vitro 3D systems mimicking the target tissue or organ and thus recapitulating the tridimensional structure and microenvironment experienced by cells in vivo. Interestingly, certain tissues are known to be regulated by endogenous bioelectrical cues, in addition to chemical and mechanical cues. One such tissue is the bone. It has, indeed, been demonstrated to exhibit piezoelectric properties in vivo, with electrical signaling playing a role in its formation during the early embryo developmental stages. Electrical stimulation has been proven to sustain cell proliferation and to boost the expression of relevant genes and induce higher levels of enzymatic activities related to bone matrix deposition. Herein, we describe the development of a 3D model of bone tissue based on the conductive polymer PEDOT:PSS and human adipose derived stem cells. 3D electroactive porous scaffolds have been produced using the ice-templating technique, and different compositions (different ratios of conductive polymer to Collagen Type 1) have been explored. The developed scaffolds as well as cells interaction and response have been characterized. Overall, the results obtained so far highlight the usefulness of the porous conductive scaffolds as an in vitro platform for the development of 3D models for bone tissue engineering

Introduction. Complete or nearly complete disruption of the gluteus attachment is seen in 10–20% of cases at the time of total hip arthroplasty (THA). Special attention is needed to identify the lesion at the time of surgery because the avulsion often is visible only after a thickened hypertrophic trochanteric bursa is removed. The purpose of this study was to evaluate a technique designed to restore abductor function by transferring the gluteus maximus to compensate for the deficient medius and minimus muscles. Methods. From Jan 1 2009 to Dec 31 2013, 525 primary THAs were performed by the author. After the components were implanted, the greater trochanteric bursa was removed, and the gluteus medius and minimus attachments to the greater trochanter were visualized and palpated. Ninety-five hips (95 patients) were found to have damaged muscle attachments to bone. Fifty-four hips had mild damage consisting of splits in the tendon, but no frank avulsion of abductor tendon from the bone attachment. None had severe atrophy of the abductor muscles, but all had partial fatty infiltration. All hips with this mild lesion had repair of the tendons with #5 Ticron sutures to repair the tendon bundles together, anchored to the greater trochanter. Forty-one hips had severe damage with complete or nearly complete avulsion of the gluteus medius and minimus muscles from their attachments to the greater trochanter. Thirty-five of these hips had partial fatty infiltration of the abductor muscles, but all responded to electrical stimulation. The surface of the greater trochanter was denuded of soft tissue with a rongeur, the muscles were repaired with five-seven #5 Ticron mattress sutures passed through drill holes in the greater trochanter, and a gluteus maximus flap was transferred to the posterior third of the greater trochanter and sutured under the vastus lateralis. Six hips had complete detachment of the gluteus medius and minimus muscles, severe atrophy of the muscles, and poor response of the muscles to electrical stimulation. The gluteus medius and minimus muscles were sutured to the greater trochanter, and the gluteus maximus flap was transferred. Postoperatively, patients were instructed to protect the hip for 8 weeks, then abductor exercises were started. Results. The normal hips all had negative Trendelenburg tests at 2 and 5 years postoperative with mild lateral hip pain reported by 11 patients at 2 years, and 12 patients at 5 years. In the 54 with mild abductor tendon damage treated with simple repair, positive Trendelenburg test was found in 5 hips at 2 years and in 8 hips at 5 years. Lateral hip pain was reported in 7 hips at 2 years, and in 22 at 5 years. In the 35 hips with severe avulsion but good muscle tissue, who had repair with gluteus maximus flap transfer, all had good abduction against gravity and negative Trendelenburg tests at 2 and 5 years postoperative, and none had lateral hip pain. Of the 6 hips with complete avulsion and poor muscle who underwent abductor muscle repair and gluteus maximus flap transfer, all had weak abduction against gravity, mildly positive Trendelenburg sign, and mild lateral hip pain at 2 and 5 years postoperative. Conclusions. Abductor avulsion is uncommon but not rare, and is detected during THA only by direct examination of the tendon and removal of the trochanteric bursa. Simple repair of mild abductor tendon damage did not prevent progressive abductor weakness in some hips; and the increase in number of patients with lateral hip pain from 2 to 5 years suggests progressive deterioration. Augmentation of the repair with a gluteus maximus flap appears to provide stable reconstruction of the abductor muscles, and seemed to restore function in the hips with functioning muscles

Aims

The aims of this study were to investigate any possible relationship between a preoperative sensitivity to pain and the degree of pain at rest and on exertion with postoperative function in patients who underwent stemless total shoulder arthroplasty (TSA).

Objectives

Emerging evidence indicates that tendon disease is an active process with inflammation that is critical to disease onset and progression. However, the key cytokines responsible for driving and sustaining inflammation have not been identified.