Potential healthcare resource use and associated costs of every 2 month injectable cabotegravir plus rilpivirine long-acting regimen implementation in the Spanish National Healthcare System compared to daily oral HIV treatments.

INTRODUCTION: HIV treatment currently consists of daily oral antiretroviral therapy (ART). Cabotegravir + rilpivirine long-acting (CAB + RPV LA) is the first ART available in Spain administered every 2 months through intramuscular injection by a healthcare professional (HCP). The objective of this analysis was to assess potential healthcare resource use (HRU) and cost impact of implementing CAB + RPV LA vs. daily oral ART at National Health System (NHS) hospitals. METHODS: Online quantitative interviews and cost analysis were performed. Infectious disease specialists (IDS), hospital pharmacists (HP) and nurses were asked about their perception of potential differences in HRU between CAB + RPV LA vs. daily oral ART, among other concepts of interest. Spanish official tariffs were applied as unit costs to the HRU estimates (€2022). RESULTS: 120 responders (n = 40 IDS, n = 40 HP, n = 40 nurses) estimated an average number of annual visits per patient by speciality (IDS, HP, and nurse, respectively) of 3.3 vs. 3.7; 4.4 vs. 6.2; 6.1 vs. 3.9, for CAB + RPV LA vs. daily oral ART, and 3.0 vs. 3.2; 4.8 vs. 5.8; 6.9 vs. 4.9, respectively when adjusting by corresponding specialist responses. Estimation by the total sample led to an annual total cost per patient of €2,076 vs. €2,473, being €2,032 vs. €2,237 after adjusting by corresponding HCP, for CAB + RPV LA vs. daily oral ART. CONCLUSIONS: These results suggest that the implementation of CAB + RPV LA in NHS hospitals would not incur in increased HRU-related costs compared to current daily oral ARTs, being potentially neutral or even cost-saving.

An injectable oleogel-based bupivacaine formulation for prolonged non-opioid post-operative analgesia.

Opioid-based medications remain the mainstay of post-operative pain management, even though they are associated with a plethora of adverse effects including addiction, nausea, constipation, cognitive impairment, respiratory depression, and accidental death due to overdose. Local anesthetics are effective at controlling the intense pain after surgery but their short duration of effect limits their clinical utility in post-operative pain management. In this manuscript, an optimized injectable oleogel-based formulation of bupivacaine for multi-day post-operative pain management was characterized on the benchtop and assessed in two clinically-relevant porcine post-operative pain models. Benchtop characterization verified the optimized oleogel-based bupivacaine formulation design, demonstrating a homogenous stable oleogel with sufficient injectability due to shear-thinning properties, high drug loading capacity and first-order drug release kinetics over 5 days. In vivo assessment in two pig post-operative pain models demonstrated that the oleogel-based bupivacaine formulation can provide statistically significant multi-day analgesia in two routes of administration: local instillation directly into a surgical site and ultrasound-guided peripheral nerve block injection. Pharmacokinetic assessment of ALX005 found that Cmax values were not statistically different from the bupivacaine HCl control, with no clinical signs of local anesthetic systemic toxicity observed, when administering up to 2.7 and 8.1 times the control dose of bupivacaine HCl. This study demonstrates the pre-clinical safety and efficacy of an injectable oleogel-based bupivacaine formulation and explores its utility as a single-administration long-acting local anesthetic product for post-operative pain management that can be used in both local and regional anesthetic applications.

Injectable citrate-based polyurethane-urea as a tug-of-war-inspired bioactive self-expansive and planar-fixing screw augmented bone-tendon healing.

Inspired by tug-of-war, a game-changing bone-tendon fixation paradigm was developed. Specifically, injectable citrate-based bioactive self-expansive and planar-fixing screw (iCSP-Scr) consisting of reactive isocyanate (NCO) terminalized citrate-based polyurethane, proanthocyanidin modified hydroxyapatite (HAp) and water (with/without porogen) was developed and administrated in the bone-tendon gap. Instead of the "point to point" tendon fixation by traditional interface screws, along with the moisture-induced crosslinking and expansion of iCSP-Scr within the confined space of the irregularly shaped bone-tendon gap, the tendon graft was evenly squeezed into the bone tunnel in a "surface to surface" manner to realize strong and stable bone-tendon fixation via physical expansion, mechanical interlocking and chemical bonding (between -NCO and the -NH2, -SH groups on bone matrix). The optimized iCSP-Scr exhibited rapid crosslinking, moderate expansion rate, high porosity after crosslinking, as well as tunable elasticity and toughness. The iCSP-Scr possessed favorable biodegradability, biocompatibility, and osteoinductivity derived from citrate, PC and HAp, it was able to promote osteogenesis and new bone growth inward of bone tunnel thus further enhanced the bone/iCSP-Scr mechanical interlock, ultimately leading to stronger tendon fixation (pull-out force 106.15 ± 23.15 N) comparing to titanium screws (93.76 ± 17.89 N) after 14 weeks' ACL reconstruction in a rabbit model. The iCSP-Scr not only can be used as a self-expansive screw facilitating bone-tendon healing, but also can be expanded into other osteogenic application scenarios.

Evaluating the impact of COVID-19 on medication adherence and health care utilization among individuals with psychotic disorders who are prescribed long-acting injectables (LAIs) or clozapine: A population-based study in Manitoba, Canada.

BACKGROUND: Ongoing psychiatric follow-up and medication adherence improve outcomes for patients with psychotic disorders. Due to COVID-19, outpatient care may have been disrupted, impacting healthcare utilization. METHODS: A retrospective population-wide study was conducted for adults in Manitoba, Canada. Medication adherence and healthcare utilization were examined from 2019 to 2021. The presence of a diagnosed psychotic disorder was identified in the five years before the index date in each year. The LAI and clozapine cohorts consisted of those who received at least two prescriptions in each year 180 days before the March 20th index date. The change in adherence was measured using the average Medication Possession Ratio. Healthcare utilization rates were compared using Generalized Estimating Equation models. RESULTS: There were no significant differences between LAI and clozapine discontinuation rates before and during the pandemic. In the LAI cohort, general practitioner visits decreased significantly (-3.5 %, p = 0.039) across four quarters of 2021 versus 2019. All-cause hospitalizations decreased by 16.8 % in 2020 versus 2019 (p = 0.0055), while psychiatric hospitalizations decreased by 18.7 % across four quarters in 2020 (p = 0.0052) and 13.7 % in 2021 (p = 0.0425), versus 2019 in the LAI cohort. There was a significant transition to virtual care during the first wave of COVID-19 (71 % in clozapine, 51 % in LAI cohorts). Trends in total outpatient visits and non-psychiatric hospitalizations remained stable. CONCLUSION: COVID-19 had no substantial impact on LAI and clozapine discontinuation rates for patients previously adherent. Outpatient care remained stable, with a significant proportion of visits being done virtually at the outset of the pandemic.

An injectable biomimetic hydrogel adapting brain tissue mechanical strength for postoperative treatment of glioblastoma without anti-tumor drugs participation.

Adapting the mechanical strength between the implant materials and the brain tissue is crucial for the postoperative treatment of glioblastoma. However, no related study has been reported. Herein, we report an injectable lipoic acid­iron (LA-Fe) hydrogel (LFH) that can adapt to the mechanical strength of various brain tissues, including human brain tissue, by coordinating Fe3+ into a hybrid hydrogel of LA and its sodium salt (LANa). When LFH, which matches the mechanical properties of mouse brain tissue (337 ± 8.06 Pa), was injected into the brain resection cavity, the water content of the brain tissue was maintained at a normal level (77%). Similarly, LFH did not induce the activation or hypertrophy of glial astrocytes, effectively preventing brain edema and scar hyperplasia. Notably, LFH spontaneously degrades in the interstitial fluid, releasing LA and Fe3+ into tumor cells. The redox couples LA/DHLA (dihydrolipoic acid, reduction form of LA in cells) and Fe3+/Fe2+ would regenerate each other to continuously provide ROS to induce ferroptosis and activate immunogenic cell death. As loaded the anti-PDL1, anti-PDL1@LFH further enhanced the efficacy of tumor-immunotherapy and promoted tumor ferroptosis. The injectable hydrogel that adapted the mechanical strength of tissues shed a new light for the tumor postoperative treatment.

Long-acting antipsychotic treatments: focus on women with schizophrenia.

Effective management of schizophrenia (SZ) requires long-term treatment with antipsychotics (APs) to prevent clinical relapse, attain remission and improve patients' personal and social functioning, and quality of life. Although APs remain the cornerstone treatment for patients with SZ, despite their potential benefits, long-acting injectable APs (LAI-APs) remain underused, most notably in women with SZ. The efficacy and tolerability of APs differ significantly between men and women, and some of these differences are more noticeable depending on the patient's age and the stage of the disorder. Although sex differences may influence treatment outcomes in SZ, their pertinence has been insufficiently addressed, especially regarding the use of LAI-APs. Some biological and social experiences, such as pregnancy, lactation, contraception and menopause, are specific to women, but these remain under-researched issues. Implications of this disorder in parenting are also of special pertinence regarding women; therefore, taking sex differences into account when treating SZ patients is now recommended, and improving personalized approaches has been proposed as a priority in the management of psychosis. In this narrative, critical review, we address some aspects specific to sex and their implications for the clinical management of women with SZ, with a special focus on the potential role of LAI-AP treatments.

• Schizophrenia is a chronic mental illness, and patients often need to take antipsychotic medications in the long-run in order to stay well, avoid re-occurrence of symptoms and improve their everyday functioning and quality of life. • Antipsychotics are available in both pill and injection form. The latter is known as long-acting injectable antipsychotics (LAI-APs) and can be administered from weekly to twice a year. • Despite their effectiveness and practicality due to less frequent administration, LAI-APs remain largely underused, especially in women with schizophrenia. • The efficacy and tolerability of antipsychotics can be very different between men and women, and some of these differences may be more pronounced depending on the patient's age and the phase of the illness. • Notably, physical and social aspects such as pregnancy, lactation, contraception, parenting and menopause and their effects on the treatment with antipsychotics and particularly LAI-APs in women with schizophrenia are under-studied. • Nevertheless, we have now become more aware of the importance of these sex differences, and it is recommended to take them routinely into consideration when treating patients with schizophrenia in clinical practice. • In this article, we discuss how factors specific to sex can influence the treatment of women with schizophrenia and focus on the potential role of LAI-AP medications.

Long-Acting Injectable Pre-Exposure Prophylaxis Perceptions and Preferences Among Transgender and Nonbinary Young Adults in the United States.

Long-acting injectable pre-exposure prophylaxis for HIV prevention (LAI-PrEP) was approved for use in the United States in 2021, yet little is known about perceptions of LAI-PrEP among transgender and nonbinary young adults, a group that faces substantial barriers to HIV prevention. We investigated US transgender and nonbinary young adults' perceptions of and attitudes toward LAI-PrEP and how perceived advantages and disadvantages of LAI-PrEP related to the PrEP continuum of care. We conducted semi-structured interviews with 31 transgender and nonbinary young adults who reported oral PrEP use or were PrEP-eligible. We analyzed responses using both a deductive RADaR approach, to identify LAI-PrEP perceptions relevant to the PrEP continuum of care, and an inductive thematic analysis to explore key themes. In this study, all PrEP-experienced and most PrEP-naïve participants indicated an interest in LAI-PrEP, citing advantages over daily oral medication (e.g., fewer adherence challenges). Three key themes emerged: (1) Some participants linked perceived advantages of LAI-PrEP to experiences with gender-affirming care (e.g., familiarity with needles via hormone use). (2) Participants weighed trade-offs and contextual factors that influenced their LAI-PrEP preferences (e.g., interest contingent on whether location for receiving injection was geographically accessible). (3) Participants envisaged alternative delivery methods that could enhance LAI-PrEP acceptability and uptake (e.g., home injection). HIV prevention programs should incorporate the insights of transgender and nonbinary young adults to ensure that emerging HIV prevention technologies are accessible and responsive to the needs and concerns of people of all gender modalities.

Barriers to Oral PrEP: A Qualitative Study of Female Sex Workers, PrEP Prescribers, Policymakers, and Community Advocates in Morocco.

In 2017, Morocco became the first Arab country to incorporate pre-exposure prophylaxis (PrEP) in its HIV-prevention program. Yet no research has been published on PrEP from Morocco. Although female sex workers are one of the target populations of PrEP in Morocco, their enrollment in PrEP is lower than men who have sex with men. In this study, we conducted 38 semi-structured interviews with female sex workers, physicians who prescribe PrEP, policymakers, and community advocates to identify problems associated with access to and use of PrEP. We also investigated preferences for daily oral, vaginal ring, and long-acting injectable PrEP. A reflexive thematic analysis revealed seven themes: PrEP stigma; stigmatization and criminalization of sex work; one size doesn't fit all; knowledge and misconceptions about PrEP; economic burden; inconvenience of PrEP pills; and preferred PrEP modalities. This paper discusses the implications of the findings for increasing access and use of PrEP in Morocco.

Factors that Influence Uptake of Oral PrEP among Female Sex Workers One of the most recent scientific advancements in the history of the HIV pandemic was the introduction of pre-exposure prophylaxis (PrEP). However, the uptake of PrEP in the Arab world is low. In this paper we interviewed female sex workers, physicians who prescribe PrEP, policymakers, and community advocates to identify problems associated with access to and use of PrEP. Several barriers were identified including stigma attached to PrEP, misconceptions about PrEP, and financial burden. Although most female sex workers in our study were interested in using PrEP, the delivery methods of PrEP should be tailored to fit the lifestyle and personal circumstances of potential users.

Thermo-sensitive Poloxamer based antibacterial anti-inflammatory and photothermal conductive multifunctional hydrogel as injectable, in situ curable and adjustable intraocular lens.

Cataract patients look forwards to fewer postoperative complications and higher vision quality after surgery. However, the current intraocular lens (IOL) implanted after cataract surgery neither can adjust focal length in response to ciliary muscle contraction as natural lens nor have the ability to prevent postoperative complications. Herein, a thermosensitve Poloxamer based hybrid hydrogel with antibacterial anti-inflammatory and photothermal functional elements doping was designed and used as injectable, in situ curable, and adjustable IOL (FHTAB IOL). The FHTAB IOL was composed of thermosensitve triblock-polymer F127DA and a small amount of HAMA, combined with BP NS, TA, and Ag NPs. FHTAB IOL can be injected into the empty lens capsule after cataract surgery via an injectable thermos-gel under NIR illumination and then be rapidly cured to form a full-size IOL under short-time blue light irradiation. The designed injectable FHTAB IOL possesses high transparency and transmittance, with a refractive index similar to the natural lens and adjustable properties. It was stabilized as a refractive medium without any leakage in the eye. In addition, the TA and Ag NPs loaded in the FHTAB IOL displayed significant antibacterial and anti-inflammatory effects in vitro and vivo. This study presents a potentially effective new strategy for the development of multifunctional adjustable IOLs.

Injectable Dual Fenton/Enzymatically Cross-Linked Double-Network Hydrogels Based on Acrylic/Phenolic Polymers with Highly Reinforced and Tunable Mechanical Properties.

Injectable hydrogels have been extensively used as promising therapeutic scaffolds for a wide range of biomedical applications, such as tissue regeneration and drug delivery. However, their low fracture toughness and brittleness often limit their scope of application. Double-network (DN) hydrogel, which is composed of independently cross-linked rigid and ductile polymer networks, has been proposed as an alternative technique to compensate for the weak mechanical properties of hydrogels. Nevertheless, some challenges still remain, such as the complicated and time-consuming process for DN formation, and the difficulty in controlling the mechanical properties of DN hydrogels. In this study, we introduce a simple, rapid, and controllable method to prepare in situ cross-linkable injectable DN hydrogels composed of acrylamide (AAm) and 4-arm-PPO-PEO-tyramine (TTA) via dual Fenton- and enzyme-mediated reactions. By varying the concentration of Fenton's reagent, the DN hydrogels were rapidly formed with controllable gelation rate. Importantly, the DN hydrogels showed a 13-fold increase in compressive strength and a 14-fold increase in tensile strength, compared to the single network hydrogels. The mechanical properties, elasticity, and plasticity of DN hydrogels could also be modulated by simply varying the preparation conditions, including the cross-linking density and reagent concentrations. At low cross-linker concentration (<0.05 wt %), the plastic DN hydrogel stretched to over 6,500%, whereas high cross-linker concentration (≥0.05 wt %) induced fully elastic hydrogels, without hysteresis. Besides, DN hydrogels were endowed with rapid self-recovery and highly enhanced adhesion, which can be further applied to wearable devices. Moreover, human dermal fibroblasts treated with DN hydrogels retained viability, demonstrating the biocompatibility of the cross-linking system. Therefore, we expect that the dual Fenton-/enzyme-mediated cross-linkable DN hydrogels offer great potential as advanced biomaterials applied for hard tissue regeneration and replacement.

Recent advances on thermosensitive hydrogels-mediated precision therapy.

Precision therapy has become the preferred choice attributed to the optimal drug concentration in target sites, increased therapeutic efficacy, and reduced adverse effects. Over the past few years, sprayable or injectable thermosensitive hydrogels have exhibited high therapeutic potential. These can be applied as cell-growing scaffolds or drug-releasing reservoirs by simply mixing in a free-flowing sol phase at room temperature. Inspired by their unique properties, thermosensitive hydrogels have been widely applied as drug delivery and treatment platforms for precision medicine. In this review, the state-of-the-art developments in thermosensitive hydrogels for precision therapy are investigated, which covers from the thermo-gelling mechanisms and main components to biomedical applications, including wound healing, anti-tumor activity, osteogenesis, and periodontal, sinonasal and ophthalmic diseases. The most promising applications and trends of thermosensitive hydrogels for precision therapy are also discussed in light of their unique features.

Role of Platelet Concentrates in Dental-Pulp Regeneration: A Systematic Review of Randomized Clinical Trials.

Statement of the Problem: Treatment of immature necrotic teeth is a problematic situation. Conventional root canal therapy is challenging and leaves a weak, fragile, and undeveloped tooth for lifetime. Purpose: This review was aimed to assess the outcome of available randomized clinical trials (RCTs) on the efficacy of platelet concentrates (PC) in dentine-pulp complex regeneration. Materials and Method: In this systematic review, an electronic search was conducted on MEDLINE, EMBASE, Cochrane, and Google scholar databases. A further manual search was performed on the list of related articles in order to ensure inclusion of potentially missed articles in earlier electronic search. Those proved RCTs matched with the standard criteria were included following an initial assessment of abstracts and the text independently by the reviewers. Results: From the total 602 harvested articles, only 13 met the criteria and were evaluated with 11 having parallel design and 2 split mouth. Only one study featured low risk of bias, while three had moderate risk and the rest were at high risk of bias. Six studies had used platelet rich plasma (PRP), 4 employed platelet rich fibrin (PRF), one utilized injectable platelet rich fibrin (I-PRF), and three used both PRF and PRP for their experimental groups while blood clot (BC) was used as the control group for all. The success rate was reported at 87.3% judged by the absence of pathologic signs and symptoms. Conclusion: Dentin wall thickening, root lengthening and apex closure were higher in PC groups, however, these differences were not statistically significant in reported studies. It can be concluded that PCs promote the pulp tissue revitalization and continuation of root development. However, a consensus on its potency for true pulp regeneration is yet to be reached.

Long-acting injectable ART to advance health equity: a descriptive analysis of US clinic perspectives on barriers, needed support and programme goals for implementation from applications to the ALAI UP Project.

INTRODUCTION: Approval of the first long-acting injectable antiretroviral therapy (LAI ART) medication heralded a new era of HIV treatment. However, the years since approval have been marked by implementation challenges. The "Accelerating Implementation of Multilevel Strategies to Advance Long-Acting Injectable for Underserved Populations (ALAI UP Project)" aims to accelerate the systematic and equitable delivery of LAI ART. METHODS: We coded and analysed implementation barriers according to the Consolidated Framework for Implementation Research (CFIR) domains, desired resources and programme goals from questionnaire short-answer responses by clinics across the United States responding to ALAI UP's solicitation to participate in the project between November 2022 and January 2023. RESULTS: Thirty-eight clinics responded to ALAI UP's solicitation. The characteristics of LAI ART as an innovation (cost, complexity of procurement, dosing interval, limited eligibility) precipitated and interacted with barriers in other CFIR domains. Barriers included obtaining coverage for the cost of medication (27/38 clinics) (outer setting); need for new workflows and staffing (12/38) and/or systems to support injection scheduling/coordination (16/38), transportation and expanded clinic hours (13/38) (inner setting); and patient (10/38) and provider (7/38) education (individuals). To support implementation, applicants sought: technical assistance to develop protocols and workflows (18/38), specifically strategies to address payor challenges (8/38); additional staff for care coordination and benefits navigation (17/38); opportunities to share experiences with other implementing clinics (12/38); patient-facing materials to educate and increase demand (7/38); and support engaging communities (6/38). Clinics' LAI ART programme goals varied. Most prioritized delivering LAI ART to their most marginalized patients struggling to achieve viral suppression on oral therapy, despite awareness that current US Food and Drug Administration approval is only for virally suppressed patients. The goal for LAI ART reach after 1 year of implementation ranged from ≤10% of patients with HIV on LAI ART (17/38) to ≥50% of patients (2/38). CONCLUSIONS: Diverse clinic types are interested in offering LAI ART and most aspire to use LAI ART to support their most vulnerable patients sustain viral suppression. Dedicated resources centred on equity and relevant to context and population are needed to support implementation. Otherwise, the introduction of LAI ART risks exacerbating, not ameliorating, health disparities.

Physiologically-Based Pharmacokinetic Modeling and In Vitro-In Vivo Correlation of TV-46000 (Risperidone LAI): Prediction from Dog to Human.

The interest in the development and therapeutic application of long-acting injectable products for chronic or long-term treatments has experienced exponential growth in recent decades. TV-46000 (Uzedy, Teva) is a long-acting subcutaneous (sc) injectable formulation of risperidone, approved for the treatment of schizophrenia in adults. Following sc injection, the copolymers together with risperidone precipitate to form a sc depot under the skin to deliver therapeutic levels of risperidone over a prolonged period of either 1 month or 2 months, depending upon the dose. This work presents the strategy and the results of the physiologically-based pharmacokinetic (PBPK) modeling and establishing of in vitro-in vivo correlation (IVIVC) for the prediction of TV-46000 pharmacokinetic profile in humans, using in vitro release, intravenous (iv), and sc single-dose pharmacokinetic data in beagle dogs. The resulting simulated TV-46000 PK profile in humans showed that the shape of the predicted risperidone and its active metabolite 9-OH-risperidone PK profiles was different from the observed one, thus suggesting that the TV-46000 release profile was species-dependent and cannot be directly extrapolated from dog to human. In conclusion, while level A IVIVC cannot be claimed, this work combining PBPK and IVIVC modeling represents an interesting alternative approach for complex injectable formulations where classical methods are not applicable.

Extended Release of Bupivacaine from Temperature-Responsive PNDJ Hydrogels Improves Postoperative Weight-Bearing in Rabbits Following Knee Surgery.

Effective treatment of postoperative pain lasting for multiple days without opioids is an important clinical need. We previously reported analgesia lasting up to 96 h in a porcine soft tissue model of postoperative pain using SBG004, an extended-release formulation of bupivacaine based on the temperature-responsive polymer poly(N-isopropylacrylamide-co-dimethylbutyrolactone acrylamide-co-Jeffamine M-1000 acrylamide) [PNDJ]. Orthopaedic surgical sites such as the knee can involve complex sensory innervation which presents a distinct challenge to local anesthetic delivery. The purpose of this work was to evaluate the pharmacokinetics and efficacy of SBG004 in an orthopaedic surgical model in comparison to currently available local anesthetics. Pharmacokinetics following periarticular (PA) or intraarticular (IA) injection of SBG004 were compared against liposomal bupivacaine (Lip-Bupi) PA in New Zealand White rabbits (all doses 14.5 mg/kg). Analgesic efficacy of SBG004 (IA, PA, or IA + PA), three active comparators, and saline was evaluated following knee surgery in New Zealand White rabbits. Analgesia was assessed via weight-bearing on the operated limb during spontaneous large steps in video recordings. Systemic bupivacaine exposure lasted at least 7 days for SBG004 PA, 4 days for SBG004 IA, and 2 days for Lip-Bupi PA. In the analgesia study, weight-bearing in all active groups except SBG004 IA was more frequent versus saline through 8 h postoperatively (p < 0.05). Only SBG004 IA + PA resulted in a higher proportion of weight-bearing rabbits at 24 h versus saline (6/7 versus 2/10, p = 0.015). Analysis of pooled data from 24-72 h showed significantly greater frequency of weight-bearing in rabbits receiving SBG004 IA + PA (71%) versus saline (37%), ropivacaine cocktail (41%), and Lip-Bupi PA (36%). The results indicate that the release profile from SBG004 PA or IA coincides reasonably with the time course of postoperative pain, and SBG004 may produce longer duration of analgesia than local anesthetics currently used in knee surgery, including during the period of 24-72 h recognized as a target for extended-release local anesthetics.

Analysis and mapping of harm reduction research in the context of injectable drug use: identifying research hotspots, gaps and future directions.

BACKGROUND: Harm reduction is a crucial approach in addressing the multifaceted challenges of injectable drug use. This paper presents an analysis and mapping of the existing literature on harm reduction research in the context of injectable drug use. By reviewing a comprehensive set of scholarly articles, this study identifies research hotspots, knowledge gaps, and future directions in the field. The findings provide valuable insights for researchers, policymakers, and practitioners to guide future research efforts and inform evidence-based harm reduction interventions. METHODS: Data for the study was obtained from the Scopus database, using keywords and phrases related to harm reduction and injectable drug use. Validation methods were employed to verify the accuracy and comprehensiveness of the search strategy. Data analysis involved identifying growth patterns, key contributors, mapping frequent terms, identifying research hotspots, and identifying emerging research directions. RESULTS: A total of 971 articles were found, with a notable increase from 2015 to 2022. The International Journal of Drug Policy (n = 172, 17.7%) and the Harm Reduction Journal (n = 104, 10.7%) were the most prolific journals, and the United States (n = 558, 57.5%) had the highest number of publications. The Johns Hopkins University (n = 80, 8.5%) was the most prolific institution. Mapping of frequent author keywords revealed the main keywords, including harm reduction, HIV, hepatitis C, and opioid overdose. The highly cited articles cover a broad time span and focus on topics like naloxone distribution, HIV and hepatitis C transmission, while recent articles concentrate on emerging issues such as the impact of the COVID-19 pandemic, fentanyl-related concerns, stigma reduction, and needle and syringe programs. Both sets of articles share a common focus on harm reduction strategies, but recent publications highlight current challenges and developments in the field. CONCLUSIONS: This study provides insights into research landscape on harm reduction in injectable drug use. Research is concentrated in high-income countries, emphasizing the need for more research in low- and middle-income countries. Recent publications focus on emerging challenges like COVID-19 and fentanyl. Research gaps highlight the need for studies in diverse populations, social determinants, program evaluation, and implementation strategies to enhance harm reduction interventions.

An injectable adhesive hydrogel for photothermal ablation and antitumor immune activation against bacteria-associated oral squamous cell carcinoma.

Pathogenic bacteria are closely associated with the occurrence, development and metastasis of oral squamous cell carcinoma (OSCC). Antibacterial therapy has been considered an enhancement strategy to suppress bacteria-associated tumors and promote anti-tumor immune responses. Herein, we developed an injectable adhesive hydrogel, PNIPAM/DL@TIR, for the in situ photothermal ablation and robust stimulation of antitumor immunity against OSCC colonized by Porphyromonas gingivalis (Pg), one of the major oral pathogenic bacteria. PNIPAM/DL@TIR, composed of poly(N-isopropylacrylamide), demethylated lignin, and TAT peptide-conjugated IR820, was prepared using a simple dissolve-dry-swell solvent exchange method. Upon 808 nm laser irradiation, PNIPAM/DL@TIR exerted photothermal effects to ablate Pg-colonized OSCC and generate dual tumor and bacterial antigens. Owing to its large number of catechol groups, PNIPAM/DL@TIR efficiently captured these antigens to form an in situ antigen repository, thereby eliciting robust and durable antitumor immune responses. Proteomic analysis revealed that the captured antigens comprised both tumor neoantigens and bacterial antigens. The catechol groups endowed PNIPAM/DL@TIR with antioxidant activity, which was also conducive to stimulating antitumor immunity. Altogether, this study develops an injectable adhesive hydrogel and provides a combination strategy for treating bacteria-associated OSCC. STATEMENT OF SIGNIFICANCE: In this study, we developed an injectable adhesive hydrogel, PNIPAM/DL@TIR, for in situ photothermal ablation and robust stimulation of antitumor immunity against OSCC colonized by Porphyromonas gingivalis, one of the major oral pathogenic bacteria. PNIPAM/DL@TIR, which consists of poly(N-isopropylacrylamide), demethylated lignin, and TAT peptide-conjugated IR820 exhibited outstanding photothermal performance. Owing to the presence of catechol groups, PNIPAM/DL@TIR has good bioadhesive properties and can capture protein antigens to form in situ antigen repository, thus initiating robust and long-term antitumor immune responses. In addition, PNIPAM/DL@TIR exhibited strong antioxidant activity that is favorable for promoting antitumor immunity. In the mouse model of OSCC with bacterial infection, PNIPAM/DL@TIR not only ablated the primary tumors upon NIR laser irradiation, but also induced tumor and bacterial vaccination in situ to suppress distant tumors and lung metastasis.

Modular and Photoreversible Polymer-Nanoparticle Hydrogels via Host-Guest Interactions.

Polymer-nanoparticle (PNP) hydrogels are a class of nanocomposite materials showing potential as injectable platforms for biomedical applications. Their design is limited by incomplete knowledge of how the binding motif impacts the viscoelastic properties of the material and is generally constrained to non-responsive supramolecular interactions. Expanding the scope of available interactions and advancing the understanding of how defined interactions influence network formation would accelerate PNP hydrogel design. To address this gap in the design of PNP hydrogels, the study designs and investigates a tunable platform based on beta-cyclodextrin (ßCD) host-guest cross-links between functionalized polymers and nanoparticles. A host-functionalized polymer (ßCD hyaluronic acid) and guest harboring block co-polymer (poly(ethylene glycol)-b-poly(lactic acid)) NPs are synthesized. The presence and accessibility for binding of the host and guest moieties are characterized via isothermal titration calorimetry. PNP hydrogels with varying concentrations of functionalized polymer and NPs reveal a limited window of concentrations for gelation. It is hypothesized that network formation is governed by the capacity of polymer chains to effectively bridge NPs, which is related to the host-guest ratios present in the system. Further, photo-responsive guests are incorporated to engineer photoreversible gelation of PNP hydrogels via exposure to specific wavelengths of light.

Enhancing neovascularization post-myocardial infarction through injectable hydrogel functionalized with endothelial-derived EVs.

Over the past three decades, cell therapy development has fallen short of expectations, with many cellular sources demonstrating a 'Janus effect' and raising safety concerns. Extracellular vesicles (EVs), supported by advanced technologies, present a promising avenue in regenerative medicine, offering benefits such as immune tolerance and avoidance of negative aspects associated with cell transplants. Our previous research showcased enhanced and organized subcutaneous vascularization using three-dimensional bioprinted patches containing HUVEC-derived EVs in immunodeficient animal models. In this context, stress conditions on the cells of origin further boosted the EVs' neoangiogenic potential. Since neovascularization is the first regenerative target requiring restoration, the present study aims to complement our previous work by employing an injectable gelatin methacrylate (GelMA) hydrogel functionalized with HUVEC-derived EVs in a pathological condition of acute myocardial infarction. This bioactive hydrogel resulted in reduced fibrosis, improved contractility, and promoted angiogenesis, showing promise in countering tissue deterioration and addressing vascular deficits. Moreover, the molecular characterization of EVs through miRNome and proteomic analyses further supports their potential as bio-additives for hydrogel functionalization. This cell-free approach mitigates immune rejection and oncogenic risks, offering innovative therapeutic advantages.

Cation-π Interaction-Enhanced Self-Healing Injectable Hydrogels for Gastric Perforation Repair.

Surgical operations are the preferred treatment for gastric perforation (GP) but incur postoperative complications such as gastrointestinal adhesions and bacterial infections, leading to inefficient wound healing and serious complications that may even threaten the life of the patient. Developing hydrogel dressings capable of adapting to the gastric environment (acid) and decreasing visceral adhesions and bacterial infections after GP treatment is crucial. In this article, we developed an injectable, self-healing hydrogel using cation-π interactions between protonated amines and aromatic rings under acidic conditions and explored it for GP repair. The hydrogels demonstrate exceptional self-healing capabilities under acidic conditions and can be effectively tailored for the gastric environment. In addition, the hydrogel demonstrated significant efficacy in preventing gastrointestinal adhesion, reducing inflammation, promoting angiogenesis, and effectively facilitating wound healing in a rat GP model. This novel hydrogel demonstrates adaptability to the gastric environment, rendering it highly promising for potential applications in gastric trauma healing.