Early Healing Response Research Articles

Molecular Analysis of Peri-implant Soft Tissue Response to Different Abutment Materials in Humans. A Pilot Study.

To evaluate the response of human peri-implant soft tissue (PIST) on different healing abutment materials 24 hours after positioning, by assessing the expression of genes related to the early connective tissue wound healing response. Experimental abutments of 4 different materials (A): grade 4 titanium, (B) grade 5 titanium, (C) zirconia and (D) PEEK, were mounted on installed implants in 5 patients, four different abutments each. Before implant placement, a gingival biopsy (control-CT) was obtained using a 2 mm diameter punch (T0). After 24 hours (T24), PIST biopsies were collected using a specifically designed custom-made cutting device. Real-time PCR was performed to analyze the expression of the following genes: COL-I, COL-III, MMP-1, TIMP-1,TGF-b1, FN, ITGA4, ITGA5, ITGB1, RAC-1, COL-IV, aSMA, IL-6 and CXCL-1. Gene expression analysis showed some differences between CT and abutment of different materials, although no significant differences were detected comparing the experimental groups. COL-I was significantly down-regulated in groups A and C compared to CT. MMP-1 and TIMP-1 increased in all the experimental groups, although at a lower extent in group A. FN, RAC-1, COL-IV and aSMA were down-regulated, especially in group A, in which CXCL-1 and IL-6 showed the lowest expression. The results of grade 4 titanium and zirconia abutments seem to be promising, since a lower expression of genes related with inflammation, myofibroblasts activation and ECM remodeling was observed when compared with grade 5 titanium and PEEK, without triggering a pro-fibrotic response in the early phases of PIST repair.

Successive tendon injury in an in vivo rat overload model induces early damage and acute healing responses.

Introduction: Tendinopathy is a degenerative condition resulting from tendons experiencing abnormal levels of multi-scale damage over time, impairing their ability to repair. However, the damage markers associated with the initiation of tendinopathy are poorly understood, as the disease is largely characterized by end-stage clinical phenotypes. Thus, this study aimed to evaluate the acute tendon responses to successive fatigue bouts of tendon overload using an in vivo passive ankle dorsiflexion system. Methods: Sprague Dawley female rats underwent fatigue overloading to their Achilles tendons for 1, 2, or 3 loading bouts, with two days of rest in between each bout. Mechanical, structural, and biological assays were performed on tendon samples to evaluate the innate acute healing response to overload injuries. Results: Here, we show that fatigue overloading significantly reduces in vivo functional and mechanical properties, with reductions in hysteresis, peak stress, and loading and unloading moduli. Multi-scale structural damage on cellular, fibril, and fiber levels demonstrated accumulated micro-damage that may have induced a reparative response to successive loading bouts. The acute healing response resulted in alterations in matrix turnover and early inflammatory upregulations associated with matrix remodeling and acute responses to injuries. Discussion: This work demonstrates accumulated damage and acute changes to the tendon healing response caused by successive bouts of in vivo fatigue overloads. These results provide the avenue for future investigations of long-term evaluations of tendon overload in the context of tendinopathy.

Patient Reported Outcome of Palatal Donor Site After Harvesting Connective Tissue Graft With or Without Platelet-rich Fibrin: A Prospective Clinical Study

Aim: To evaluate the palatal donor site after harvesting connective tissue graft with or without platelet-rich fibrin (PRF). Material and Methods: Forty-two patients requiring connective tissue grafting were randomly divided into two groups: the experimental palatal donor site ( n = 21) received PRF before suturing, and the control palatal donor site ( n = 21) was sutured without any PRF. Results: Among 42 enrolled patients requiring connective tissue grafting, 34 patients completed the study. After 10 days, there was an increase in the average thickness of the palatal surgical test site in PRF-treated patients, whereas it decreased in non-PRF-treated patients. Patients’ response and acceptance for the surgical treatment modality in terms of Patient Comfort Score (PCS) and Patient Appearance Score (PAS) showed less discomfort and better/pleasing appearance in the experimental group after treatment as compared with the control group. “Absolute contour match” of the healing lesion to adjacent mucosa was observed in 76.5% of experimental sites, and no “absolute contour match” was observed with the adjacent non-surgical tissue in the control group, whereas, at 3 and 12 weeks, a 100% “absolute match” with the adjacent tissue was observed for all esthetic parameters in both groups. Conclusion: PRF usage at the donor site seems to be a simple less-invasive approach of high significance resulting in more accelerated physiological healing phenomenon and better early healing response.

Early tissue and healing responses after maxillary sinus augmentation using horizontal platelet rich fibrin bone blocks

BackgroundThe effects of horizontal platelet-rich fibrin (H-PRF) bone block on the healing and immune response during sinus augmentation have not been fully investigated histologically at early time points.MethodsEighteenth male New Zealand white rabbits underwent bilateral sinus augmentation and were divided into two groups: deproteinized bovine bone mineral (DBBM) alone and H-PRF + DBBM (H-PRF bone block) group. Maxilla samples were collected at 3, 7 and 14 days post sinus augmentation procedures and analyzed using histological staining for the number of inflammatory cells, new blood vessels and evidence for early osteoclast bone turnover/remodeling. Furthermore, the effects of H-PRF bone blocks on the migration of osteoblasts and THP-1 macrophages were evaluated using a Transwell assay in vitro.ResultsA higher number of immune cells were found in the H-PRF bone block group at 3 and 7 days post-surgery when compared to the DBBM alone group,most notably in the regions close to the mucosal lining and bone plates. Furthermore, a significantly greater number of new blood vessel formations and early signs of osteoclast development were found in the H-PRF bone block group at 14 days. The in vitro transwell assay further confirmed that culture medium from H-PRF bone block markedly promote the migration of osteoblasts and THP-1 macrophages.ConclusionsThe findings from this study have shown that H-PRF bone block is capable of increasing early immune cell infiltration leading to the acceleration of neovascularization and speeding the process of bone metabolism in vivo following maxillary sinus grafting with DBBM.

The effects of NF-κB suppression on the early healing response following intrasynovial tendon repair in a canine model.

The highly variable clinical outcomes noted after intrasynovial tendon repair have been associated with an early inflammatory response leading to the development of fibrovascular adhesions. Prior efforts to broadly suppress this inflammatory response have been largely unsuccessful. Recent studies have shown that selective inhibition ofIkappaB kinase beta(IKK-β), an upstream activator ofnuclear factor kappa-light chain enhancer of activated B cells(NF-κB) signaling, mitigates the early inflammatory response and leads to improved tendon healing outcomes. In the current study, we test the hypothesis that oral treatment with the IKK-β inhibitor ACHP (2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-4-yl nicotinenitrile an inhibitor) will modulate the postoperative inflammatory response and improve intrasynovial flexor tendon healing. To test this hypothesis, the flexor digitorum profundus tendon of 21 canines was transected and repaired within the intrasynovial region and assessed after 3 and 14 days. Histomorphometry, gene expression analyses, immunohistochemistry, and quantitative polarized light imagingwere used to examine ACHP-mediated changes. ACHP led to reduction in phosphorylated p-65, indicating that NF-κB activity was suppressed. ACHP enhanced expression of inflammation-related genes at 3 days and suppressed expression of these genes at 14 days. Histomorphometry revealed enhanced cellular proliferation and neovascularization in ACHP-treated tendons compared with time-matched controls. These findings demonstrate that ACHP effectively suppressed NF-κB signaling and modulated early inflammation, leading to increased cellular proliferation and neovascularization without stimulating the formation of fibrovascular adhesions. Together, these data suggest that ACHP treatment accelerated the inflammatory and proliferative phases of tendon healing following intrasynovial flexor tendon repair. Clinical Significance: Using a clinically relevant large-animal model, this study revealed that targeted inhibition of nuclear factor kappa-light chain enhancer of activated B cellssignaling with ACHP provides a new therapeutic strategy for enhancing the repair of sutured intrasynovial tendons.

Early vascular healing after neXt-generation drug-eluting stent implantation in Patients with non-ST Elevation acute Coronary syndrome based on optical coherence Tomography guidance and evaluation (EXPECT): study protocol for a randomized controlled trial.

There is limited evidence about vessel wall healing response following implantation of next-generation drug-eluting stents (DES) in patients admitted with a non-ST elevation acute coronary syndrome (NSTE-ACS). Cumulative data indicate that optical coherence tomography (OCT) imaging can optimize percutaneous coronary intervention results and expedite stent endothelialization in the general population but there is lack of data in NSTE-ACS patients. The EXPECT study is an investigator-initiated, prospective, randomized trial to assess early vascular healing response following next-generation DES implantation in patients admitted with NSTE-ACS based on OCT guidance and evaluation. Sixty patients are randomized at 1:1:1 ratio to OCT-guided percutaneous coronary intervention (PCI) with 3-month follow-up OCT imaging (O3 group, n = 20), to angiography-guided PCI with 3-month follow-up OCT imaging (A3 group, n = 20) and to angiography-guided PCI with 6-month follow-up OCT imaging (A6 group, n = 20). The primary endpoint of the study is stent strut coverage rate at 3- or 6- month follow-up in the studied groups. The secondary endpoints of the study include OCT imaging endpoints, clinical endpoints, and molecular biology endpoints at the different time points. The clinical endpoints comprised of major cardiovascular adverse events and individual components. The molecular biology endpoints comprised of lipid levels and the levels of inflammatory indicators. The findings of the EXPECT study are anticipated to provide novel insights into vessel wall healing in NSTE-ACS population following implantation of next-generation DES, underscore the value of OCT imaging in expediting strut coverage in this setting, and explore the potential of an early discontinuation of dual antiplatelet therapy (DAPT) in this population. ClinicalTrials.gov, NCT04375319.

Engineered Platelet‐Derived Growth Factor‐Releasing Hydrogels Promote Fetal Membrane Healing In Vivo

AbstractFetoscopic interventions to treat fetal anomalies are currently performed for a variety of conditions. Depending on the procedure, preterm rupture of the fetal membranes (FMs) happens in around 30% of the cases, potentially leading to preterm birth and fetal morbidity and mortality. Here, the capacity of modular transglutaminase crosslinked poly(ethylene glycol) (TG‐PEG) hydrogels that release platelet‐derived growth factor (PDGF)‐BB to promote FM healing is described. In vitro, such growth factor‐loaded hydrogels are able to stimulate amniotic cell migration and proliferation. When applied in vivo, these TG‐PEG hydrogels tightly seal the FM and uterus defects created by a fetoscope and remain stable for 10 days. The migration of healing‐related cells into such hydrogels in the myometrium, endometrium, and FM areas is only possible in soft TG‐PEG hydrogels. Importantly, bioengineered hydrogels releasing PDGF‐BB promote recruitment of host cells from the myometrium and the endometrium, and to a lesser extent from FM areas. In such hydrogels, the potent proliferation and matrix production of the recruited cells at the site of treatment into the biomaterial initiates a robust early healing response. PDGF‐BB‐loaded TG‐PEG hydrogels hold great promise for the treatment of fetoscopy‐induced FM defects and for the prevention of preterm birth.

Abstract 14778: Combined Shear Stress-Molecular Imaging for the Evaluation of Early Arterial Healing Responses Following Implantation of Bioresorbable Scaffold With Different Strut Thickness

Introduction and Hypothesis: Arterial healing following stent implantation involves a series of biological reactions such as thrombosis, inflammation, neointimal regeneration. Clinical evidences have shown favorable arterial healing after thin-strut stents, however, there has been a lack of in vivo imaging evidence on how strut thickness affect vascular healing process. We evaluated local endothelial shear stress (ESS) and healing response of a thin-strut bioresorbable scaffold (BRS, 100μm) compared to first-generation 157μm-thickness ABSORB. Methods and Results: BRS and ABSORB were simultaneously implanted in left coronary arteries of the same pigs (n=7). Detailed scaffolded-artery 3D model was reconstructed based on OCT and angiography. Scaffold-related inflammation response was serially assessed by dual-modal OCT-near-infrared fluorescence (OCT-NIRF) molecular imaging using macrophage-mannose receptor-Cy7 as an inflammation-targeting agent. On ESS analysis, regions with athero-prone low ESS were significantly greater in thick-ABSORB compared to BRS. Dual-modal OCT-NIRF imaging visualized arterial inflammation activity at peri-strut regions in vivo (Figure). Based on coregistered ESS-NIRF data, we found a significant inverse correlation was found between ESS and NIRF activity (p<0.0001), suggesting immune-modulating effect of ESS during early stent healing phase. Arterial inflammation, quantified as target-to-background ratio, was significantly lower in thin-strut BRS than ABSORB at 2 weeks (p<0.01). At week 3, unlike ABSORB with residual peri-strut NIRF signals, inflammation activity dissipated significantly in BRS. Ex vivo confocal fluorescence microscopy (Figure) and immunohistochemical analysis well corroborated the findings in vivo . Conclusions: Thin-strut BRS was associated with less inflammation and rapid resolution of inflammation compared to thicker-strut ABSORB. This study provides in vivo imaging insights into how strut thickness affects early arterial healing and the importance of ESS as an inflammatory modulator. Our comprehensive imaging strategy enabling evaluation of complex interplay between scaffold, ESS, and artery is expected to enhance understanding of stent healing.

Flexor Tendon Injury and Repair. The Influence of Synovial Environment on the Early Healing Response in a Canine Model.

Environmental conditions strongly influence the healing capacity of connective tissues. Well-vascularized extrasynovial tendons typically undergo a robust wound-healing process following transection and repair. In contrast, avascular intrasynovial tendons do not mount an effective repair response. The current study tests the hypothesis that flexor tendons, as a function of their synovial environment, exhibit unique inflammatory, angiogenic, and metabolic responses to injury and repair. Flexor tendons present a distinct opportunity to test the study hypothesis, as they have proximal regions that are extrasynovial and distal regions that are intrasynovial. In an internally controlled study design, the second and fifth forepaw flexor tendons were transected and repaired in either the extrasynovial or the intrasynovial anatomical region. Histological, gene expression, and proteomics analyses were performed at 3 and 7 days to define the early biological events that drive synovial environment-dependent healing responses. Uninjured intrasynovial tendons were avascular, contained high levels of proteoglycans, and expressed inflammatory factors, complement proteins, and glycolytic enzymes. In contrast, extrasynovial tendons were well vascularized, contained low levels of proteoglycans, and were enriched in inflammation inhibitors and oxidative phosphorylation enzymes. The response to injury and repair was markedly different between the 2 tendon regions. Extrasynovial tendons displayed a robust and rapid neovascularization response, increased expression levels of complement proteins, and an acute shift in metabolism to glycolysis, whereas intrasynovial tendons showed minimal vascularity and muted inflammatory and metabolic responses. The regional molecular profiles of intact and healing flexor tendons revealed extensive early differences in innate immune response, metabolism, vascularization, and expression of extracellular matrix as a function of the synovial environment. These differences reveal mechanisms through which extrasynovial tendons heal more effectively than do intrasynovial tendons. To improve outcomes after operative repair, future treatment strategies should promote features of extrasynovial healing, such as enhanced vascularization and modulation of the complement system and/or glucose metabolism.

Early vascular healing following bioresorbable-polymer sirolimus-eluting stent implantation in comparison with durable-polymer everolimus-eluting stent: sequential optical coherence tomography study

Abstract Background Orsiro ultrathin-strut bioresorbable-polymer sirolimus-eluting stent (BP-SES) might facilitate early vascular healing responses that seems to be associated with improved long-term clinical outcomes. We compared the early vascular healing responses to BP-SES and Xience durable-polymer everolimus-eluting stent (DP-EES) in patients with chronic coronary syndrome (CCS) using optical coherence tomography (OCT). Methods A total of 40 patients with CCS receiving OCT-guided PCI were included. 20 patients were assigned to BP-SES, and 20 to DP-EES. OCT was performed immediately after stent placement (post-procedure) and at 1 month follow-up. Struts were recorded as uncovered if any part was visibly exposed in the lumen or covered if a layer of tissue covered all reflecting surfaces. The incidence of intrastent thrombus (IS-Th) and irregular protrusion (IRP) were also assessed. Results At 1 month, the percentage of uncovered struts was significantly lower in the BP-SES compared with the DP-EES (2.8±1.6% vs. 5.8±1.8%, respectively; p<0.001), and that of malapposed struts was similar between both groups (2.5±3.1% vs. 2.4±2.2%; p=0.76). There were no differences in the incidence of IS-Th (65.0% vs. 55.0% at post-procedure; p=0.54, 30.0% vs. 35.0% at 1 month; p=0.75) and IRP (30.0% vs. 25.0% at post-procedure; p=0.74). IRP had completely resolved at 1 month in both groups. Conclusion Early vascular healing response to Orsiro BP-SES implantation was revealed in CCS patients at 1 month compared with Xience DP-EES. Orsiro BP-SES may have a potential to shorten the dual antiplatelet therapy duration. Funding Acknowledgement Type of funding source: None

The acromioclavicular ligament shows an early and dynamic healing response following acute traumatic rupture

PurposeSymptomatic horizontal instability is clinically relevant following acute acromioclavicular joint dislocations. However, the intrinsic healing response is poorly understood. The present study sought to investigate time-dependent healing responses of the human acromioclavicular ligament following acute traumatic rupture.MethodsBiopsies of the acromioclavicular ligament were obtained from patients undergoing surgical treatment for acute acromioclavicular joint dislocations. Specimens were stratified by time between trauma and surgery: group 1, 0–7 days (n = 5); group 2, 8–14 days (n = 6); and group 3, 15–21 days (n = 4). Time-dependent changes in cellularity, collagen (type 1 and 3) concentration, and histomorphological appearance were evaluated for the rupture and intact zone of the acromioclavicular ligament.ResultsGroup 1 was characterized by cellular activation and early inflammatory response. The rupture zone exhibited a significantly higher count of CD68-positive cells than the intact zone (15.2 vs 7.4; P ≤ 0.05). Consistently, synovialization of the rupture end was observed. Within the second week, the rupture zone was subject to proliferation showing more fibroblast-like cells than the intact zone (66.8 vs 43.8; P ≤ 0.05) and a peak of collagen type 3 expression (group 1: 2.2 ± 0.38, group 2: 3.2 ± 0.18, group 3: 2.8 ± 0.57; P ≤ 0.05). Signs of consolidation and early remodeling were seen in the third week.ConclusionsThe acromioclavicular ligament exhibits early and dynamic healing responses following acute traumatic rupture. Our histological findings suggest that surgical treatment of acute ACJ dislocations should be performed as early as possible within a timeframe of 1 week after trauma to exploit the utmost biological healing potential. Prospective clinical studies are warranted to investigate whether early surgical treatment of ACJ dislocations translates into clinical benefits.

Gastric perforation in a dog: Postmortem computed tomography and forensic autopsy findings

Abstract The aim of this case report is to describe the postmortem computed tomography (PMCT) and forensic autopsy investigation findings of a case of antemortem gastric perforation in a dog. A 13-year-old, spayed female, pit bull type dog with a recent history of limping, anorexia, and lethargy, was treated with unknown doses of an unknown corticosteroid, grapiprant (a veterinary nonsteroidal anti-inflammatory drug [NSAID]), and omeprazole, prior to euthanasia. PMCT was subsequently completed, followed by confirmatory forensic autopsy. On PMCT images, a full thickness gastric wall discontinuity with confluent luminal and extraluminal gas (pneumoperitoneum) was identified. In the absence of expected additional sites of postmortem intracavitary gas accumulation (pleural, peri-cardial, and intra-articular) the pneumoperitoneum was attributed primarily to antemortem gastric rupture, which precipitated patient decline and subsequent euthanasia. Forensic autopsy revealed gastric ulceration with perforation. Histological evaluation of the perforation site revealed suppurative inflammation and an early healing response. The combined findings of the PMCT and autopsy were compatible with antemortem gastric perforation attributable to the historical concurrent administration of a NSAID and corticosteroid. Given adequate radiologist knowledge and training, antemortem gastric perforation may be differentiated from postmortem gastromalacia with rupture.

Investigation of the early healing response to dicationic imidazolium-based ionic liquids: a biocompatible coating for titanium implants.

Dicationic Imidazolum-based ionic liquids with amino acid anions (IonL) have been proposed as a multifunctional coating for titanium dental implants, as their properties have been shown to address multiple early complicating factors while maintaining host cell compatibility. This study aims to evaluate effects of this coating on host response in the absence of complicating oral factors during the early healing period using a subcutaneous implantation model in the rat. IonLs with the best cytocompatibility and antimicrobial properties (IonL-Phe, IonL-Met) were chosen as coatings. Three different doses were applied to cpTi disks and subcutaneously implanted into 36 male Lewis rats. Rats received 2 implants: 1 coated implant on one side and an uncoated implant on the contralateral sides (n=3 per formulation, per dose). Peri-implant tissue was evaluated 2 and 14 days after implantation with H&E staining and IHC markers associated with macrophage polarization as well as molecular analysis (qPCR) for inflammatory and healing markers. H&E stains revealed the presence of the coating, blood clots and inflammatory infiltrate at 2 days around all implants. At 14 days, inflammation had receded with more developed connective tissue with fibroblasts, blood vessels in certain doses of coated and uncoated samples with no foreign body giant cells. This study demonstrated that IonL at the appropriate concentration does not significantly interfere with and healing and Ti foreign body response. Results regarding optimal dose and formulation from this study will be applied in future studies using an oral osseointegration model.

Prospective multicentre open-label randomised controlled trial of 3-month versus 12-month dual antiplatelet therapy after implantation of the new generation biodegradable polymer sirolimus TARGET-eluting coronary stent: protocol of the TARGET DAPT trial

IntroductionDual antiplatelet therapy (DAPT) with aspirin and thienopyridine is required after placement of coronary stents to prevent thrombotic complications. However, current recommendation for duration of DAPT remains controversial. Firehawk is...

Compromised Bone Healing in Aged Rats Is Associated With Impaired M2 Macrophage Function.

Fracture repair is initiated by a multitude of immune cells and induction of an inflammatory cascade. Alterations in the early healing response due to an aged adaptive immune system leads to impaired bone repair, delayed healing or even formation of non-union. However, immuno-senescence is not limited to the adaptive immunity, but is also described for macrophages, main effector cells from the innate immune system. Beside regulation of pro- and anti-inflammatory signaling, macrophages contribute to angiogenesis and granulation tissue maturation. Thus, it seems likely that an altered macrophage function due to aging may affect bone repair at various stages and contribute to age related deficiencies in bone regeneration. To prove this hypothesis, we analyzed the expression of macrophage markers and angiogenic factors in the early bone hematoma derived from young and aged osteotomized Spraque Dawley rats. We detected an overall reduced expression of the monocyte/pan-macrophage markers CD14 and CD68 in aged rats. Furthermore, the analysis revealed an impaired expression of anti-inflammatory M2 macrophage markers in hematoma from aged animals that was connected to a diminished revascularization of the bone callus. To verify that the age related disturbed bone regeneration was due to a compromised macrophage function, CD14+ macrophage precursors were transplanted locally into the osteotomy gap of aged rats. Transplantation rescued bone regeneration partially after 6 weeks, demonstrated by a significantly induced deposition of new bone tissue, reduced fibrosis and significantly improved callus vascularization.

Procedural findings and early healing response after implantation of a self-apposing bioresorbable scaffold in coronary bifurcation lesions.

We aimed to evaluate feasibility, early healing and self-correcting properties of the Desolve 150 bioresorbable scaffold (BRS) implanted in bifurcation lesions, using the simple, provisional side branch (SB) stenting technique. BIFSORB pilot was a proof-of-concept study enrolling 10 patients with stable angina pectoris and a bifurcation lesion with SB ≥ 2.5mm and less than 50% diameter stenosis. Procedure and 1-month outcome was evaluated by optical coherence tomography (OCT) to assess scaffold performance and healing patterns. Nine patients were treated with Desolve 150 BRS and one delivery to the target bifurcation failed. Thrombus formation in the jailed SB ostium was seen in three cases, but was completely resolved at 1-month. OCT confirmed acute self-correcting properties. No clinical events were reported after six months. Scaffold diameter by OCT increased in the proximal main vessel from 3.09 ± 0.16mm to 3.34 ± 0.18mm (p = 0.01) and in distal main vessel from 2.82 ± 0.26mm to 3.02 ± 0.29mm (p < 0.01) at one-month follow-up. SB ostial diameter stenosis improved from 42 ± 15% to 34 ± 12% (p = 0.01). Malapposition was effectively reduced after 1 month from 4.1 (1.4; 6.1)% to 0.1 (0; 0.6)% (p = 0.002). Treatment of bifurcation lesions using Desolve 150 BRS was feasible except for a delivery failure and unsettling thrombus formation behind jailing SB struts, which was completely resolved at 1-month. Self-correcting and even self-expanding properties were confirmed.

Fixation of periprosthetic or osteoporotic distal femoral fractures with locking plates: a pilot randomised controlled trial

IntroductionWe hypothesised that the use of a polyaxial locking plate design offers the same clinical benefits as a monoaxial locking plate system following distal femoral osteoporotic/periprosthetic fracture fixation.MethodA multicentre prospective randomised pilot trial was conducted. Inclusion criteria were patients over 60 years with a displaced osteoporotic or periprosthetic distal femoral fracture. Details documented included time to union, complications, reinterventions and functional outcomes according to the Oxford knee score and EuroQol EQ-5D. Analysis of factors influencing an early fracture healing response was performed between those with clear features of radiological callus formation at three months. Statistical analysis was performed using a logistic regression model with multiple covariates assessed for each plate system (1:1 ratio) over a follow-up period of one year.ResultsForty patients (34 females) with a mean age of 77 (60–99) were recruited. Four patients deceased within the first six months. Twenty-five patients united by the six month follow-up. Six more patients progressed to union between six and nine months. Five patients developed non-union (two patients had implant failure; one in each group) and all underwent revision surgery. Malunion was evident in two cases, one with 15° of valgus (monoaxial plate), and one with 12° of recurvatum (polyaxial plate). Between the two plate systems, statistical analysis revealed no significant differences in most of the recorded parameters. Radiological features of early bone healing were present when the surgical approach was smaller (p = 0.015), and when a greater working length of the bridging plate was present (p = 0.016).ConclusionBoth plate systems demonstrated good union rates and limited implant related complications. Good reduction, mechanically sound construct and respect of the local fracture biology was more important than the particular plate design characteristics.

Blastema formation and periosteal ossification in the regenerating adult mouse digit.

While mammals cannot regenerate amputated limbs, mice and humans have regenerative ability restricted to amputations transecting the digit tip, including the terminal phalanx (P3). In mice, the regeneration process is epimorphic and mediated by the formation of a blastema comprised of undifferentiated proliferating cells that differentiate to regenerate the amputated structures. Blastema formation distinguishes the regenerative response from a scar-forming healing response. The mouse digit tip serves as a preclinical model to investigate mammalian blastema formation and endogenous regenerative capabilities. We report that P3 blastema formation initiates prior to epidermal closure and concurrent with the bone histolytic response. In this early healing response, proliferation and cells entering the early stages of osteogenesis are localized to the periosteal and endosteal bone compartments. After the completion of stump bone histolysis, epidermal closure is completed and cells associated with the periosteal and endosteal compartments blend to form the blastema proper. Osteogenesis associated with the periosteum occurs as a polarized progressive wave of new bone formation that extends from the amputated stump and restores skeletal length. Bone patterning is restored along the proximal-distal and medial digit axes, but is imperfect in the dorsal-ventral axis with the regeneration of excessive new bone that accounts for the enhanced regenerated bone volume noted in previous studies. Periosteum depletion studies show that this compartment is required for the regeneration of new bone distal to the original amputation plane. These studies provide evidence that blastema formation initiates early in the healing response and that the periosteum is an essential tissue for successful epimorphic regeneration in mammals.

Randomised comparison of vascular response to biodegradable polymer sirolimus eluting and permanent polymer everolimus eluting stents: An optical coherence tomography study

BackgroundDrug-eluting stents with biodegradable polymer coatings have shown promising outcomes in randomised studies. MethodsWe compared neointimal healing patterns including strut coverage and assessed neointimal maturity using a novel algorithm in coronary lesions treated with sirolimus-eluting stents with biodegradable polymer coating (BP-SES) or everolimus eluting stents with permanent polymer coating (PP-EES) using optical coherence tomography after 6months. ResultsA total of 39 patients were randomised to BP-SES (n=19) or PP-EES (n=20) for the treatment of coronary lesions. Of those, 29 patients (14 BP-SES and 15 PP-EES) underwent optical coherence tomography (OCT) and angiography at 6-month follow-up. Tissue coverage and apposition were assessed in a total of 6162 struts (BP-SES, n=2889; PP-EES, n=3273). Neointimal maturity was assessed in 3672 neointimal regions above struts using grey scale intensity analysis. OCT analysis showed neointimal coverage of 2433 (BP-SES) vs. 2702 (PP-EES) struts (84.2% vs. 82.6%, p=0.70), whereas the remainder was uncovered after 6months. Mean neointimal thickness did not differ significantly between groups (54.3±7.8μm vs. 80±14.6μm, p=0.12). The rate of malapposed struts was comparable between groups (1.3% vs. 2.2%, p=0.27). Grey scale signal intensity analysis showed mature tissue coverage of struts in 46.2% in BP-SES vs. 31.8% in PP-EES (p=0.31) of neointimal regions. ConclusionThe present study showed comparable early vascular healing response characterised by neointimal coverage with mainly immature neointima in both BP-SES and PP-EES.

Impact of sleep restriction on local immune response and skin barrier restoration with and without "multinutrient" nutrition intervention.

Systemic immune function is impaired by sleep restriction. However, the impact of sleep restriction on local immune responses and to what extent any impairment can be mitigated by nutritional supplementation is unknown. We assessed the effect of 72-h sleep restriction (2-h nightly sleep) on local immune function and skin barrier restoration of an experimental wound, and determined the influence of habitual protein intake (1.5 g·kg-1·day-1) supplemented with arginine, glutamine, zinc sulfate, vitamin C, vitamin D3, and omega-3 fatty acids compared with lower protein intake (0.8 g·kg-1·day-1) without supplemental nutrients on these outcomes. Wounds were created in healthy adults by removing the top layer of less than or equal to eight forearm blisters induced via suction, after adequate sleep (AS) or 48 h of a 72-h sleep restriction period (SR; 2-h nightly sleep). A subset of participants undergoing sleep restriction received supplemental nutrients during and after sleep restriction (SR+). Wound fluid was serially sampled 48 h postblistering to assess local cytokine responses. The IL-8 response of wound fluid was higher for AS compared with SR [area-under-the-curve (log10), 5.1 ± 0.2 and 4.9 ± 0.2 pg/ml, respectively; P = 0.03]; and both IL-6 and IL-8 concentrations were higher for SR+ compared with SR ( P < 0.0001), suggestive of a potentially enhanced early wound healing response. Skin barrier recovery was shorter for AS (4.2 ± 0.9 days) compared with SR (5.0 ± 0.9 days) ( P = 0.02) but did not differ between SR and SR+ ( P = 0.18). Relatively modest sleep disruption delays wound healing. Supplemental nutrition may mitigate some decrements in local immune responses, without detectable effects on wound healing rate. NEW & NOTEWORTHY The data herein characterizes immune function in response to sleep restriction in healthy volunteers with and without nutrition supplementation. We used a unique skin wound model to show that sleep restriction delays skin barrier recovery, and nutrition supplementation attenuates decrements in local immune responses produced by sleep restriction. These findings support the beneficial effects of adequate sleep on immune function. Additional studies are necessary to characterize practical implications for populations where sleep restriction is unavoidable.