Peritendinous Adhesions Research Articles

Graphene-MoS2 polyfunctional hybrid hydrogels for the healing of transected Achilles tendon.

Healing of injured tendon is a major clinical challenge in orthopaedic medicine, due to the poor regenerative potential of this tissue. Two-dimensional nanomaterials, as versatile scaffolds, have shown a great potential to support, trigger and accelerate the tendon regeneration. However, weak mechanical properties, poor functionality and low biocompatibility of these scaffolds as well as post-surgery infections are main drawbacks that limit their development in the higher clinical phases. In this work, a series of hydrogels consisting polyglycerol functionalized reduced graphene oxide (PG), polyglycerol-functionalized molybdenum disulfide (PMoS2) and PG/PMoS2 hybrid within the gelatin matrix are formulated in new scaffolds and their ability for the healing of injured Achilles tendon, due to their high mechanical properties, low toxicity, cell proliferation enhancement, and antibacterial activities is investigated. While scaffolds containing PG and PMoS2 showed a moderate tendon regeneration and anti-inflammatory effect, respectively, their hybridization into PG/PMoS2 demonstrated a synergistic healing efficiency. Along the same line, an accelerated return of tendon function with low peritendinous adhesion and low cross-sectional area in animal group treated with scaffold containing PG/PMoS2 was observed. Taking advantage of the high biocompatibility, high strength, straightforward construction and fast tendon regeneration, PG/PMoS2 can be used as a new scaffold for the future tissue engineering.

Effectiveness of Bovine Tunica Vaginalis Powder in the Prevention of Tendon Adherence Following Tendon Repair Process in Bucks

The current study was designed to investigate the efficacy of lyophilized bovine tunica vaginalis powder on peritendinous adhesion of induced defect in superficial digital flexor tendon (SDFT) in goats. The study was carried out on 18 adult bucks, the surgical procedure was done under highly aseptic conditions. Prior to surgery, animals were sedated by intramuscular injection of 2 % xylazine in a dose 0.5 mg/kg body weight, then the site of the operation is anesthetized by linear infiltration of 2% lidocaine hydrochloride. The surgical incision is made on the skin on the palmer surface of the metacarpal bone of the left forelimb to expose the (SDFT), a (0.1 depth, 0.2 width, and l Long) cm defect is made on the exposed tendon, this gap is filled with drops of sterile normal saline in (9) animals, and mentioned as a control group, while the gap of the rest (9) animals is filled with the lyophilized powder as treated group. Subcutaneous tissue was closed using absorbable suture material by simple continuous suture technique, and a simple interrupted suture mattress using non-absorbable suture material for closing the skin. The macroscopic findings exhibited a significant difference in adhesion scores between the 2nd, and 3rd periods of assessment post-operation in the first and second groups, with no significant differences between groups. The conclusion of this study is the tunica vaginalis scaffold has no obvious effect on decreasing adhesion between a tendon and surrounding tissues.

Micro- and nano-environment dual-modulated anti-tendon adhesion barrier membranes

Despite promise in preventing peritendinous adhesion, electrospun membranes face many challenges related to their complex fabrication process, untargeted/uncontrolled drug delivery and consequently low therapeutical effect. Here, a micro-and nano-environment dual-modulated barrier membrane (MNBM) with on-demand gene delivery capability is presented. Our MNBM is developed by first preparing extracellular signal-regulated kinase-2 (ERK2) siRNA-loaded gelatin methacryloyl (GelMA) nanogels via facile nano-emulsification technique, then incorporating these nanogels into poly-L-lactic acid (PLLA) fibers via simple blending electrospinning. The GelMA nanogels offer a nano-niche for ERK2-siRNA encapsulation and allow for a nano-environment controlled siRNA release by readily tuning the GelMA concentrations during nano-emulsification, while the resultant MNBM can mediate a micro-environment controlled siRNA delivery in response to the matrix metalloproteinase-2 (MMP-2) enriched micro-environment at the tendon repair site. Such MNBM can not only biologically orchestrate fibroblast behaviors by silencing the target gene expression, but also physically shield the tendon from extrinsic cell/tissue invasion. This study provides a proof-of-concept of anti-adhesion barrier membrane as an intelligent gene delivery system to offer a spatiotemporal and biophysical dual control over tendon recovery according to disease state and ensure long-term therapeutic efficacy. We envision such MNBM represents a promising therapeutic platform with great efficacy to achieve adhesion-free tendon repair.

A Natural Hydrogel with Prohealing Properties Enhances Tendon Regeneration.

Tendon regeneration and reduction of peritendinous adhesion remain major clinical challenges. This study addresses these challenges by adopting a unique hydrogel derived from the skin secretion of Andrias davidianus (SSAD) and taking advantage of its biological effects, adhesiveness, and controllablemicrostructures. The SSAD-derived hydrogel contains many cytokines, which could promote tendon healing. In vitro, leach liquid of SSAD powder could promote tendon stem/progenitor cells migration. In vivo, the SSAD-derived hydrogel featuring double layers possesses strong adhesiveness and could reconnect ruptured Achilles tendons of Sprague-Dawley rats without suturing. The intimal SSAD-derived hydrogel, with a pore size of 241.7±21.0µm, forms the first layer of the hydrogel to promote tendon healing, and the outer layer SSAD-derived hydrogel, with a pore size of 3.3±1.4µm, reducing peritendinous adhesion by serving as a dense barrier. Additionally, the SSAD-derived hydrogel exhibits antioxidant and antibacterial characteristics, which further contribute to the reduction of peritendinous adhesion. In vivo studies suggest that the SSAD-derived hydrogel reduces peritendinous adhesion, increases collagen fiber deposition, promotes cell proliferation, and improves the biomechanical properties of the regenerated tendons, indicating better functional restoration. The SSAD-derived bilayer hydrogel may be a feasible biomaterial for tendon repair in the future.

Prevention of peritoneal adhesions formation by core-shell electrospun ibuprofen-loaded PEG/silk fibrous membrane

Adhesion bands are pathological fibrous tissues that create in the middle of tissues and organs, often reasons of intestinal obstruction, and female infertility. Here, we explored the anti-adhesive and inflammatory capacities of PEG/silk and Ibuprofen-loaded PEG/Silk core-shell nanofibrous membranes, respectively. The ibuprofen-loaded Silk Fibroin-Poly ethylene Glycol (SF-PEG) core-shell membrane was fabricated by electrospinning and considered in terms of morphology, surface wettability, drug release, and degradation. To reveal the membrane capability for adhesion bands inhibition, the membrane was stitched among the abdominal partition and peritoneum and then evaluated using two scoring adhesion systems. According to results, the fibrous membrane hindered cell proliferation, and the scoring systems and pathology showed that in a rat model, Ibuprofen-loaded PEG/Silk core-shell membrane caused a lightening in post-operative adhesion bands and the low-grade inflammatory reaction in animal models. Collectively, we fabricated new ibuprofen-loaded PEG/SF membranes with anti-adhesion and anti-inflammation properties. Moreover, this core-shell electrospun fibrous membrane has not even now been used to prevent peritendinous adhesion generation.

Penrose Drain Interposition - A Novel Approach to Preventing Adhesion Formation after Tenolysis.

Peritendinous adhesions represent a common problem without a satisfactory solution despite several studies. We have been using a conventional silicone Penrose drain in patients undergoing tenolysis in the hand since 2006. The Penrose drain is wrapped around the segment of the tendon after tenolysis. Therapy is started on the second post-operative day and the Penrose drain removed after one week in the outpatient clinic. We have had good outcomes with this technique. It is inexpensive, readily available and effective. Level of Evidence: Level V (Therapeutic).

Nanofibrous polycaprolactone/chitosan membranes for preventing postsurgical tendon adhesion.

Peritendinous adhesion is considered a major postsurgical tendon complication in hand surgery. This complication could be mitigated partially through early tendon mobilization. However, development of new treatment modalities to guide tissue regeneration and to reduce postsurgical tendon adhesion has recently gained attentions. In this article, synthesis and characterization of electrospun nanofibrous membranes (NFMs) of polycaprolactone (PCL) and chitosan to form a physical barrier against cellular migration leading to tendon adhesion is presented. The mechanical properties of the NFMs are modulated to maintain high integrity during postsurgical tendon mobilization. The tensile strength of the NFMs is examined in wet and dry conditions after 1000 cyclic pull loadings. In addition, the mechanical strength of the NFMs is evaluated after a degradation period of 30 days. To obtain NFM with desired properties, concentrations of polymer solutions, operation parameters of electrospinning and the thickness of NFMs were optimized. Based on the biodegradation and mechanical evaluations, the optimum NFM was obtained for specified amounts of PCL (5wt %) + chitosan (2wt %) at an electrospinning drum speed of 400 rpm. The engineered NFM could withstand forces of 33 and 19 N before and after 1000 pull cycles that are sufficient during tendon healing process. The bonding of chitosan fibers over PCL nanofibers allowed for production of NFMs with appropriate mechanical integrity and degradation rate. In vitro cell culture tests demonstrated that PCL/chitosan could only have minor impact on decreasing fibroblast attachment over the membranes probably due to protonation of amine groups.

Prevention of postoperative adhesions after flexor tendon repair with acellular dermal matrix in Zones III, IV, and V of the hand: A randomized controlled (CONSORT-compliant) trial.

Background:Various techniques have been attempted for preventing postoperative flexor tendon adhesion, such as modification of suture technique, pharmacological agents, and mechanical barriers. However, there is no evidence of the efficacy of these methods in clinical settings. In this study, we present the long-term outcomes of a randomized prospective study in which acellular dermal matrix (ADM) was used to prevent postoperative adhesions after tendon injury in the hand.Methods:From January 2017 to January 2020, all patients with an acute single flexor tendon injury in hand Zones III, IV, or V were candidates. A single-digit, total tendon rupture repaired within 48 hours, from the index finger to the little finger, was included in the study. Patients were randomly allocated to either a control or ADM group. Complications and the range of movements were recorded. Functional outcomes and a patient satisfaction questionnaire were evaluated after 12 months following the tendon repair surgery. The present study is adhered to the CONSORT guidelines.Results:A total of 25 patients was enrolled in the study: 13 patients in the ADM group and 12 in the control group. According to Buck-Gramcko II criteria, the postoperative functional outcome score was 14.38 ± 1.71 in the ADM group and 13.08 ± 1.82 in the control group (P value = .0485). Patient satisfaction was recorded at 8.38 ± 1.44 in the ADM group and 7.08 ± 1.58 in the control group (P value = .0309), a significant difference. There were no differences in complications between the 2 groups.Conclusion:The beneficial effects of ADM after tendon repair were confirmed by improved postoperative functional outcome at flexor Zones III, IV, and V, preventing peritendinous adhesions and acting effectively as an anti-adhesive barrier.

Preliminary in vivo study of biodegradable PLA-PEU-PLA anti-adhesion membranes in a rat Achilles tendon model of peritendinous adhesions.

Peritendinous adhesions are complications known to occur up to 6 weeks after surgery and cause chronic pain and disability. Anti-adhesion barriers are currently the best option for prevention. In a previous study, we designed two biodegradable membranes, D-PACO1 and D-PACO2, based on new triblock copolymers and conducted in vitro evaluations. The membranes maintained filmogenic integrity, had degradation rates that promoted anti-adhesion and were biocompatible, suggesting their safe and effective use as anti-adhesion devices. To test this hypothesis, we conducted a preliminary in vivo study in a rat model of peritendinous adhesions and evaluated the membranes' degradation rates, tendon healing and anti-adhesion effect compared to non-surgical and surgical control groups 2 and 10 weeks after surgery. Macroscopic evaluation showed membranes were effective in reducing the extent and severity of adhesions. Membranes acted as physical barriers at 2 weeks and underwent a complete or significant biodegradation at 10 weeks. D-PACO2 had a longer degradation rate compared to D-PACO1, was more effective in reducing adhesions and is expected to be more effective in promoting tendon healing. The tendency of D-PACO1 to promote tendon healing while D-PACO2 did not interfere with healing highlights the need to redesign the porosity of the D-PACO membranes for optimal nutrient diffusion, while maintaining their anti-adhesion effect and clinical usability. Preliminary findings revealed that adhesions form beyond the 6 weeks cited in the literature. In this study, adhesion formation continued for up to 10 weeks, underlining the need to increase the experimental period and sample size of future experiments evaluating anti-adhesion membranes.

Self-Healing Hydrogel Embodied with Macrophage-Regulation and Responsive-Gene-Silencing Properties for Synergistic Prevention of Peritendinous Adhesion.

Antiadhesion barriers such as films and hydrogels used to wrap repaired tendons are important for preventing the formation of adhesion tissue after tendon surgery. However, sliding of the tendon can compress the adjacent hydrogel barrier and cause it to rupture, which may then lead to unexpected inflammation. Here, a self-healing and deformable hyaluronic acid (HA) hydrogel is constructed as a peritendinous antiadhesion barrier. Matrix metalloproteinase-2 (MMP-2)-degradable gelatin-methacryloyl (GelMA) microspheres (MSs) encapsulated with Smad3-siRNA nanoparticles are entrapped within the HA hydrogel to inhibit fibroblast proliferation and prevent peritendinous adhesion. GelMA MSs are responsively degraded by upregulation of MMP-2, achieving on-demand release of siRNA nanoparticles. Silencing effect of Smad3-siRNA nanoparticles is around 75% toward targeted gene. Furthermore, the self-healing hydrogel shows relatively attenuated inflammation compared to non-healing hydrogel. The mean adhesion scores of composite barrier group are 1.67 ± 0.51 and 2.17 ± 0.75 by macroscopic and histological evaluation, respectively. The proposed self-healing hydrogel antiadhesion barrier with MMP-2-responsive drug release behavior is highly effective for decreasing inflammation and inhibiting tendon adhesion. Therefore, this research provides a new strategy for the development of safe and effective antiadhesion barriers.

Electrospun tube reduces adhesion in rabbit Achilles tendon 12\xa0weeks post-surgery without PAR-2 overexpression

One great challenge in surgical tendon repair is the minimization of peritendinous adhesions. An electrospun tube can serve as a physical barrier around a conventionally sutured tendon. Six New Zealand White rabbits had one Achilles tendon fully transsected and sutured by a 4-strand suture. Another six rabbits had the same treatment, but with the additional electrospun DegraPol tube set around the sutured tendon. The adhesion formation to the surrounding tissue was investigated 12 weeks post-operation. Moreover, inflammation-related protease-activated receptor-2 (PAR-2) protein expression was assessed. Finally, rabbit Achilles tenocyte cultures were exposed to platelet-derived growth factor-BB (PDGF-BB), which mimicks the tendon healing environment, where PAR-2 gene expression was assessed as well as immunofluorescent staining intensity for F-actin and α-tubulin, respectively. At 12 weeks post-operation, the partially degraded DegraPol tube exhibited significantly lower adhesion formation (− 20%). PAR-2 protein expression was similar for time points 3 and 6 weeks, but increased at 12 weeks post-operation. In vitro cell culture experiments showed a significantly higher PAR-2 gene expression on day 3 after exposure to PDGF-BB, but not on day 7. The cytoskeleton of the tenocytes changed upon PDGF-BB stimulation, with signs of reorganization, and significantly decreased F-actin intensity. An electrospun DegraPol tube significantly reduces adhesion up to twelve weeks post-operation. At this time point, the tube is partially degraded, and a slight PAR-2 increase was detected in the DP treated tendons, which might however arise from particles of degrading DegraPol that were stained dark brown. PAR-2 gene expression in rabbit tenocytes reveals sensitivity at around day 10 after injury.

Macrophage Polarization Modulated by NF-κB in Polylactide Membranes-Treated Peritendinous Adhesion.

Foreign body reactions (FBR) to implants seriously impair tissue-implant integration and postoperative adhesion. The macrophage, owing to its phenotypic plasticity, is a major regulator in the formation of the inflammatory microenvironment; NF-κB signaling also plays a vital role in the process. It is hypothesized that NF-κB phosphorylation exerts a proinflammatory regulator in FBR to polylactide membranes (PLA-M) and adhesion. First, in vitro and in vivo experiments show that PLA-M induces NF-κB phosphorylation in macrophages, leading to M1 polarization and release of inflammatory factors. The inflammatory microenvironment formed due to PLA-M accelerates myofibroblast differentiation and release of collagen III and MMP2, jointly resulting in peritendinous adhesion. Therefore, JSH-23 (a selective NF-κB inhibitor)-loaded PLA membrane (JSH-23/PLA-M) is fabricated by blend electrospinning to regulate the associated M1 polarization for peritendinous anti-adhesion. JSH-23/PLA-M specifically inhibits NF-κB phosphorylation in macrophages and exhibits anti-inflammatory and anti-adhesion properties. The findings demonstrate that NF-κB phosphorylation has a critical role in PLA-induced M1 polarization and aggravating FBR to PLA-M. Additionally, JSH-23/PLA-M precisely targets modulation of NF-κB phosphorylation in FBR to break the vicious cycle in peritendinous adhesion therapy.

A phlorotannins-loaded homogeneous acellular matrix film modulates post-implantation inflammatory responses.

Peritendinous adhesion mainly occurs between proliferating fibrous tissues and adjacent normal organs after surgery. Many physical barriers are applied to the implanted site to prevent peritendinous adhesion. However, these barriers often trigger inflammatory responses. Therefore, our study sought to develop phlorotannins-loaded cartilage acellular matrix (CAM) films as a physical barrier and investigate their inhibitory effect on inflammatory responses, which are associated with the induction of postoperative peritendinous adhesion (PAA). Our findings indicated that incorporating phlorotannin into the CAM film did not affect its unique characteristics including its thermal and spectroscopic properties. Moreover, the phlorotannins-loaded CAM films suppressed the expression of inflammatory mediators on RAW 264.7 macrophages stimulated using Escherichia coli lipopolysaccharides and exhibited an anti-inflammatory effect when implanted subcutaneously in rats. Therefore, our results highlight the potential of phlorotannins-loaded CAM films as a promising physical barrier to prevent PAA.

Prevention of peritendinous adhesions with electrospun poly (lactic acid-co-glycolic acid) (PLGA) bioabsorbable nanofiber: An experimental study

In this study, we investigated the application of poly (lactic acid-co-glycolic acid) in the rat Achilles tendon injury model for the prevention or alleviation of peritendinous adhesion and guidance of Achilles tendon regeneration. In the study, 48 rats were used and the rats were randomized by closed envelope method and divided into 4 mating groups in groups of 12. Left Achilles tendons of the non-PLGA-treated control group (groups 1 and 2) were cut and repaired. In the PLGA-treated groups (groups 3 and 4) the left Achilles tendons were cut and repaired, then PLGA bioabsorbable material was wrapped around the repair line. The rats in the 1st and 3rd groups were sacrificed at the end of the 1st month, and the rats in the 2nd and 4th groups at the end of the 2nd month. The degree of tendon adhesion in the Group 3 was lower in comparison with Group 1. Similarly, compared with Group 2, the degree of tendon adhesion in the Group 4 was lower. Inflammatory density, vascularization and fibrosis were higher in the experimental group. When the Group 3 and Group 1, and Group 2 and Group 4 were compared, adhesion length (p = 0.004, p = 0.041), adhesion characteristics (p = 0.049, p = 0.039) and adhesion severity (p = 0.007, p = 0.025) were found have statistically significant tendon healing in the PLGA-treated group, respectively. Significant difference was observed in inflammatory cell density, vascular density and fibrosis for Group 1 and Group 3, (p = 0.027, p = 0.041, p = 0.002), respectively. Similarly, significant difference was observed in inflammatory cell density, vascular density and fibrosis for Group 2 and Group 4, (p = 0.002, p = 0.027, p = 0.011), respectively. As a result, it was considered that poly (lactic acid-co-glycolic acid) material significantly reduces peritendinous adhesions, and this effect could occur with the vascular density, inflammatory density and fibrosis as indicated in histopathological examination. These data suggest that PLGA membrane has good biocompatibility and alleviates tendon adhesion after injury.

The Potential Role of Human Derived Amniotic Membrane Graft in The Repair of Induced Tendon Tear in Adult Male Albino Rat: Histological Study

Abstract Introduction Achilles tendon tears cause severe impairment in patient mobility and productivity, causing significant reduction in the quality of life. Many complications are associated with the tendon healing process such as peritendinous adhesions and excessive fibrotic scars. Unsatisfactory results appeared with the existing medical and surgical treatments to regain full tendon structure and function. Amniotic membrane is avascular, and characterized by low immunogenicity, anti-inflammatory, antiscarring properties. These criteria render it as a natural biological substitute and a novel therapeutic alternative for tendon tears. Aim: The aim of the work was to study the effect of human amniotic membrane graft application on the repair of induced Achilles tendon tear. Material and methods Fresh human amniotic membrane (AM) grafts were prepared from harvested human full-term caesarian sections-delivered placentas. Thirty adult male albino rats were divided into 3 equal groups (n = 10); group I (control group), group II (tendon tear group) and group III (AM treated group). After anesthesia, a full thickness transverse incision was induced in the rat right Achilles tendons of group II and III. Human derived amniotic membrane graft measuring 1 cm2 was applied circumferentially on the tendon tear in group III. Rats were sacrificed after 28 days. Results After the tendon tear, the untreated group (II) showed gradual accumulation of fat cells replacing the collagen bundles in focal areas. Areas of mononuclear cellular infiltration were demonstrated. The AM-treated group showed many thick parallel regularly arranged collagen fibers with a significant increase in the collagen fibers area percentage. It also showed apparent increase in tenoblasts with regular organization and apparent decrease of mononuclear inflammatory cells. Conclusion This study demonstrated the potential therapeutic role of the application of human amniotic membrane grafts in the repair of Achilles tendon tears, suggesting a future alternative therapy for patients suffering from Achilles tendon tears.

Effectiveness of Hyaluronan Autocross-Linked-Based Gel in the Prevention of Peritendinous Adherence Following Tenolysis

Peritendinous adhesions are a frequent occurrence following tenolysis and present a major clinical challenge regarding prevention and management, with no recovery assured from conservative or surgical approaches. Herein, we investigated the effectiveness of Hyaloglide®, a hyaluronan gel-based product with a novel autocross-linked technology, in a rabbit model affected by tenolysis on the flexor digitorum communis tendon (FDC). A 1.5-cm-long scrubbing of the tendon surface was performed bilaterally to induce peritendinous adhesion on FDC of 30 animals with subsequent application of Hyaloglide® on the surrounding injured area, in one randomly chosen tendon. The contralateral tendon was treated with saline solution as the control. We sacrificed the rabbit models after 45 days of surgery and quantitatively assessed the generation of peritendinous adherence and regeneration of the tendon sheaths using histological (hematossyline-eosine, masson’s trichromic), histomorphometrical (Tang score, Soslowsky Svesson, and Cook score), light electron microscopic, and gene expression investigations. Four rabbits were devoted to biomechanical analysis. Peritendinous adhesions were limited in Hyaloglide®-treated tendons; moreover, well-regenerated tendon sheaths were observed conversely to untreated tendons presenting with extensive areas of adhesions on the tendon surface. Histomorphometrical analysis revealed an adhesion score (Tang score) significantly better in the treated group (p = 0.001 *) compared to the control group. Moreover, the Soslowsky, Svensson, and Cook score parameters revealed a significantly improved regeneration for fiber structure, cellularity, and vascularity in the treated group (p = 0.001 *). No differences were reported for cartilaginous formation (p = 0.08). Gene expression analysis showed a significant increase in collagen type I expression in the treated group compared to the control group, while metalloprotease 1 and 9 were significantly increased in the control group. Biomechanical analysis did not show significant differences in both groups. Hyaloglide® treatment was safe and well-tolerated, generating improved tissue status. Local application of Hyaloglide® prevents adhesion formation after tenolysis and promotes normal healing with regeneration of the synovial sheath in a rabbit model.

Functional Hyaluronic Acid-Polylactic Acid/Silver Nanoparticles Core-Sheath Nanofiber Membranes for Prevention of Post-Operative Tendon Adhesion.

In this study, we prepared core-sheath nanofiber membranes (CSNFMs) with silver nanoparticles (Ag NPs) embedding in the polylactic acid (PLA) nanofiber sheath and hyaluronic acid (HA) in the nanofiber core. The PLA/Ag NPs sheath provides mechanical support as well as anti-bacterial and anti-inflammatory properties. The controlled release of HA from the core could exert anti-adhesion effects to promote tendon sliding while reducing fibroblast attachment. From the microfibrous structural nature of CSNFMs, they function as barrier membranes to reduce fibroblast penetration without hampering nutrient transports to prevent post-operative peritendinous adhesion. As the anti-adhesion efficacy will depend on release rate of HA from the core as well as Ag NP from the sheath, we fabricated CSNFMs of comparable fiber diameter, but with thick (Tk) or thin (Tn) sheath. Similar CSNFMs with thick (Tk+) and thin (Tn+) sheath but with embedded Ag NPs in the sheath were also prepared. The physico-chemical properties of the barrier membranes were characterized in details, together with their biological response including cell penetration, cell attachment and proliferation, and cytotoxicity. Peritendinous anti-adhesion models in rabbits were used to test the efficacy of CSNFMs as anti-adhesion barriers, from gross observation, histology, and biomechanical tests. Overall, the CSNFM with thin-sheath and Ag NPs (Tn+) shows antibacterial activity with low cytotoxicity, prevents fibroblast penetration, and exerts the highest efficacy in reducing fibroblast attachment in vitro. From in vivo studies, the Tn+ membrane also shows significant improvement in preventing peritendinous adhesions as well as anti-inflammatory efficacy, compared with Tk and Tn CSNFMs and a commercial adhesion barrier film (SurgiWrap®) made from PLA.

Dynamic exacerbation in inflammation and oxidative stress during the formation of peritendinous adhesion resulted from acute tendon injury

BackgroundPeritendinous adhesion is among the common complications after tendon injury. Numerous studies have been carried out to prevent its formation, including modifications of surgical procedures, postoperative cares, application of medicines, etc. This study dynamically monitored fluctuations of inflammation, state of oxidative stress, and histopathologic changes around injured tendon to provide theoretical basis for further exploration in mechanisms of peritendinous adhesion formation.MethodsEighteen mature Sprague-Dawley male rats were randomly allocated into 6 equal groups. Compared with control and sham group, every rat’s right hind Achilles tendon in experimental groups was cut and repaired by the modified Kessler technique. Besides control and sham group, samples of tendon margin and serum were collected at different time points after the surgery. Content of TNF-α, IL-1β, and TGF-β were assayed in harvested serum. Reactive oxygen species (ROS) were detected, expression levels of related genes (IL-1β, IL-6, SOD1, SOD2, COL1, HIF1A) were quantified by qPCR, and various histopathological evaluations were performed.ResultsIndicators (TNF-α, IL-1β, TGF-β1, ROS) were noticed to have a similar trend of significant rising 24 h after the surgery except TGF-β which was rising 72 h later. So were the expression trends of IL-1β, IL-6, SOD1, SOD2, and COL1. HIF1A, inversely correlated with SOD2, showed the progressive relief of regional tissue hypoxia. Histological evaluation showed the same tendency that fibrosis and inflammation were getting serious 48 h later after the surgery.ConclusionsInflammation, oxidative stress in injured tendon resulted from acute trauma, would be getting intense in 24 h. Peritendinous adhesion emerges and aggravates after 48 h. Thus, prompt efficient measures are advised to be taken after the injury as soon as possible.

Effect of hyperdry amniotic membrane in preventing tendon adhesion in a rabbit model

BackgroundNo anti-adhesive materials are currently in clinical use for orthopaedic surgery. We developed a hyperdry amniotic membrane (HD-AM) for easy storage and transplantation as amniotic membrane. The purpose of this study was to examine the application of HD-AM to reduce peritendinous adhesions without impairing tendon healing. MethodsWe randomly divided 3 digits (2nd, 3rd, and 4th digits) from each rabbit into three groups: a tendon repair group; a tendon repair with HD-AM group (HD-AM group); and a control group (cast only). The effects of HD-AM on peritendinous adhesions and tendon healing were examined using microscopic, histological, and mechanical analyses in a rabbit flexor digitorum profundus tendon model. ResultsAdhesions on macroscopic evaluation of the tendon repair site were significantly smaller in the HD-AM group than in the tendon repair group. Little adhesion formation or foreign body reactions were seen by on histologic evaluation in the HD-AM group. Range of motion following tendon repair was significantly better in the HD-AM group than in the tendon repair group. Maximal tensile strength required to pull the tendon from the site of adhesion was significantly smaller in the HD-AM group than in the tendon repair group. As for tendon repair site, no significant difference was seen between the tendon repair and HD-AM groups. ConclusionsHD-AM prevented peritendinous adhesion macroscopically, pathologically, and mechanically without impairing the sutured tendon. HD-AM has already been clinically applied in neurosurgery, ophthalmology, and otolaryngology, and clinical application as an anti-adhesive materials may be achieved in the future.

An oxidative stress-responsive electrospun polyester membrane capable of releasing anti-bacterial and anti-inflammatory agents for postoperative anti-adhesion

Peritendinous adhesion, secondary to the repair surgery of tendon rupture or injury, is one of the most common causes of reoperation, owing to the proliferation of fibrous tissue and excessive collagen synthesis caused by the residing inflammatory cells. In this study, a smart oxidative stress-responsive electrospun polyester membrane (EPM) was fabricated as both physical barrier and reservoir of curcumin/celecoxib (CUR/CEL) to prevent peritendinous adhesion. The multicomponent EPM was designed to release the encapsulated drugs in response to oxidative stress of the local microenvironment induced by inflammation. Specifically, sulfides in the EPM were able to react with reactive oxygen species (ROS) and become hydrophilic sulfoxide or sulfone to accelerate the release rate of drugs and regulate oxidative stress level in the inflammatory site intelligently. The oxidation-sensitive multicomponent EPM loaded with CUR and CEL was tested for anti-adhesion capacity in vitro and in vivo. An excellent ROS-sensitive degradation behavior and good cytocompatibility with cell viability of above 85% were presented with the fabricated EPM. The CUR- or CEL-loaded EPM possessed a better anti-adhesion ability compared with EPM without the drugs. Nevertheless, they were inferior to the EPM simultaneously loaded with both drugs, where the adhesion rate and fibrous adhesion number in the EPM+CUR/CEL group were close to extremely low values of about zero, demonstrating that CUR and CEL could synergistically prevent peritendinous adhesion. More interestingly, the multicomponent EPM was able to react with the local oxidative stress, leading to a smart and sustained behavior of releasing approximately 80% of the drug within 20days. Overall, the smart multicomponent EPM offers a promising barrier strategy to prevent peritendinous adhesion.