Search Results (14)

Background: Proximal hamstring tendinopathy (PHT) is a challenging overuse injury, particularly in athletes, characterized by deep buttock pain localized to the ischial tuberosity and often exacerbated by sports activities. This condition can impact an athlete’s performance, limiting high-level athletic activity. Return to sport (RTS) thus becomes a medical, physical, athletic, and economic necessity. Previous research has explored several conservative and injection-based therapies, but evidence regarding the efficacy of porcine collagen injections remains limited. Therefore, this study aims to compare the results obtained from ultrasound-guided porcine collagen injections versus a structured rehabilitation program in reducing time to return to sport (RTS) and improving Victorian Institute of Sport Assessment—Hamstring (VISA-H) scores with respect to athletes with clinically diagnosed PHT. Conservative approaches for PHT treatments include various options, such as physiotherapy, corticosteroids, plasma-rich-platelet, shockwave therapy, and collagen injection. Collagen demonstrated to be a validated option for tendinopathies treatment due its regenerative and restorative mechanism of action. Methods: Retrospective data were collected from twenty-eight athletes with a clinical diagnosis of PHT, confirmed based on pain provocation tests (Puranen–Orava, bent-knee, and modified bent-knee tests), who were divided into two groups: COL and REHAB. The VISA-H outcomes were recorded for all subjects. The COL group received three ultrasound-guided collagen injections at weekly intervals, plus standard care instructions. The REHAB group completed a progressive exercise program targeting hamstring and lumbopelvic stabilization. The primary outcomes were RTS time (days) and VISA-H scores at baseline and 8 weeks. Adverse effects were recorded. Results: The two groups of treatment were very homogeneous and showed parametric distribution concerning the biological and pathophysiological conditions. No adverse events were reported. The mean times to RTS were 57 and 72 days for COL and REHAB, respectively (p = 0.0083). The VISA-H results revealed better improvement for the COL group than the REHAB treatment (p < 0.0001), and the log-rank test showed a higher odds ratio (HR) for RTS, 5.35 (p = 0.0008), for the COL athletes. Conclusions: Ultrasound-guided porcine collagen injections, combined with standard care, significantly reduced RTS time and improved VISA-H scores compared with rehabilitation alone in athletes with PHT. However, a larger cohort of athletes might be needed to gather more information about this conservative treatment in PHT pathology. Full article

Background/Objectives: Musculoskeletal disorders causing chronic pain are increasingly prevalent due to factors such as injury, overuse, and aging, leading to interest in porcine collagen injections as a potential therapeutic and conservative option. Despite promising results, evidence-based information on this treatment is scarce. To address this gap, the authors conducted an eDelphi consensus among expert Italian physicians in musculoskeletal pain to gather their perspectives on collagen injections. Methods: A Steering Committee and a Panel of 23 physicians developed the statements list (36) including the modalities, safety, and efficacy of intra- and extra-articular collagen injections. Panelists rated their agreement with each statement on a 5-point Likert scale (5 means “Strong Agreement”). Consensus was defined as when at least 75% of the panelists voted with a score of ≥4/5 after two rounds of votes. The weighted average (WA) was calculated for each statement. As control, we elaborated a Hypothetical Parametric Distribution (HPD WA equal to 3.00), where the percent of panelists is equally distributed along each Likert Scale Value (LSV). The maximum WA for 75% of the consensus is established at 3.75. Indeed, the combination of 75% having WA > 3.75 was defined as “Strong Agreement”. While, if the consensus was under 75%, the WA vs. HPD comparison was performed using the Wilcoxon Test. Significant differences among the distribution of LSVs judged the statement as “Low Level of Agreement”. Disagreement was evaluated when the WA was under the PHD. Results: The consensus was reached “Strong Agreement” after twin rounds in 29 out of 36 (8.55%). In 5 out of 36 statements (13.89%), the panelists reached the “Low Level of Agreement” by statistical tests. In the remaining two statements, there was a “Consensus of Disagreement”. All panelists unanimously agreed on crucial points, such as contraindications, non-contraindication based solely on comorbidity, and the importance of monitoring collagen’s effectiveness. Unanimous agreement was reached on recommending ultrasound guidance and associating collagen injections with therapeutic exercise and physical modalities. Substantial consensus (concordance > 90%) supported collagen injections for osteoarthritis, chondropathy, and degenerative tendinopathies, emphasizing intra- and peri-articular treatment, even simultaneously. However, areas with limited evidence, such as the combination of collagen with other injectable drugs, treatment of myofascial syndrome, and injection frequency, showed disagreement. The potential of intra-tendinous porcine collagen injections for tendon regeneration yielded mixed results. Conclusions: Clinicians experts in musculoskeletal pain agree on using collagen injections to treat pain originating from joints (e.g., osteoarthritis) and periarticular (e.g., tendinopathies). Full article

(1) Background: Knee osteoarthritis (KOA) induces pain, stiffness, and impaired mobility, particularly in aging populations. Despite providing symptom relief, the long-term efficacy of intra-articular hyaluronic acid (HA) injections remains unclear. With its longer intra-articular residence time and potential chondroprotective effects, porcine-derived atelocollagen is an alternative to HA. We aimed to compare the safety and efficacy of collagen versus HA injections in symptomatic KOA. (2) Methods: This retrospective observational study included 40 patients with KOA who received either two cycles of collagen or HA injections at 6-month intervals. Clinical outcomes were assessed using the visual analog scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline and 6 months after the first and second injections (Cycle 1 and Cycle 2, respectively). Patient satisfaction and adverse events were recorded. Non-inferiority analysis was conducted for VAS and WOMAC score changes. (3) Results: Significant intragroup improvements in VAS and WOMAC scores were noted after each injection cycle (p < 0.05), albeit without significant between-group differences, non-inferiority of collagen to HA based on predefined margins, and comparable patient-reported satisfaction (>85% reported improvement after each cycle), with similar incidence of mild adverse events (collagen: 20%, HA: 25%, p = 0.705). (4) Conclusions: Intra-articular collagen injections were clinically non-inferior to HA in reducing pain and improving function in patients with KOA across two treatment cycles. Given its favorable safety profile and potential structural benefits, collagen may serve as a viable alternative injectable therapy for the non-surgical management of KOA. Full article

Xenogenic collagen matrices are used in clinical practice for soft tissue augmentation around teeth and implants, either alone or biofunctionalized with injectable platelet-rich fibrin (iPRF). Their direct interaction with inflammatory cells may influence both healing and destructive inflammation processes. Therefore, expression of cyclooxygenases (COX-1 and COX-2) and prostanoids (PGE2 and TXB2) was studied in THP-1 monocyte/macrophage cultures exposed to porcine collagen matrices (a non-cross-linked monolayer scaffold composed of collagen type I, collagen type III, and elastin (MLCM), a bilayer scaffold made of collagen types I and III (BLCM), and a volume-stable cross-linked monolayer scaffold (VSCM)). The study showed that VSCM and MLCM significantly reduced PGE2 concentrations in THP-1 monocyte cultures. iPRF further reduced PGE2 concentrations when exposed to MLCM. In contrast, incubation of THP-1 monocytes with VSCM and BLCM resulted in a significant increase in TXB2 concentrations compared with control conditions. Incubation of macrophages with MLCM, VSCM, and BLCM increased PGE2 concentrations, with VSCM and BLCM additionally increasing TXB2 concentrations. iPRF in macrophage cultures with VSCM and BLCM also resulted in increased PGE2 and TXB2 concentrations compared with control conditions. Confocal microscopy revealed no visible differences in COX-1 immunoexpression in monocytes and macrophages cultured with collagen matrices, either with or without iPFR. Weak positive COX-2 immunofluorescence was observed in monocytes, while moderate positive immunofluorescence was detected in macrophages. In conclusion, it can be suggested that the studied collagen matrices interact with monocytes/macrophages, with MLCM exhibiting the highest compatibility. Full article

Background/Objectives: Intervertebral disc degeneration is the most common cause of low back pain (LBP), and lumbosciatica is a major challenge to healthcare systems worldwide. For years, ozone therapy has been used with excellent results in intervertebral disc disease and in patients with LBP. In vitro studies have demonstrated the positive action of porcine collagen in extracellular matrix remodeling and homeostasis. These tissue changes, associated with LBP, may suggest an indication for combined ozone/collagen treatment in patients with LBP. However, no studies have been reported regarding this combination of treatments. Methods: The present work compared retrospective data of two treatment groups (each of 10 LBP patients): (A) oxygen–ozone therapy (OOT) vs. (B) OOT plus porcine collagen type 1 injections (COL I). Pain intensity and physiological function were assessed by the numerical rating scale (NSR) method. The Roland–Morris questionnaire was used to assess disability. Patient data were acquired before, during, and at the six-month follow-up. Significant differences were assessed by ANOVA and Student’s t-test. Results: The analyses revealed significant statistical differences comparing the two arms, where the (OOT+COL I) treatment demonstrated a booster efficacy in pain (a reduction of 62% vs. 35%), while the questionnaire revealed a reduction in disability (70% vs. 31%). Conclusions: Therefore, this combination therapy (oxygen–ozone plus porcine injectable collagen) might be a promising approach for the management of patients with LBP. Full article

Currently, an increasing number of patients are undergoing extensive surgeries to restore the mucosa of the gums in the area of recessions. The use of a connective tissue graft from the palate is the gold standard of such surgical treatment, but complications, especially in cases of extensive defects, have led to the development of approaches using xenogeneic collagen matrices and methods to stimulate their regenerative and vasculogenic potential. This study investigated the potential of a xenogeneic scaffold derived from porcine skin Mucoderm and injections of the pCMV-VEGF165 plasmid (‘Neovasculgen’) to enhance soft gingival tissue volume and vascularization in an experimental model in rabbits. In vitro studies demonstrated the biocompatibility of the matrix and plasmid with gingival mesenchymal stem cells, showing no toxic effects and supporting cell viability and metabolic activity. In the in vivo experiment, the combination of Mucoderm and the pCMV-VEGF165 plasmid (0.12 mg) synergistically promoted tissue proliferation and vascularization. The thickness of soft tissues at the implantation site significantly increased with the combined application (3257.8 ± 1093.5 µm). Meanwhile, in the control group, the thickness of the submucosa was 341.8 ± 65.6 µm, and after the implantation of only Mucoderm, the thickness of the submucosa was 2041.6 ± 496.8 µm. Furthermore, when using a combination of Mucoderm and the pCMV-VEGF165 plasmid, the density and diameter of blood vessels were notably augmented, with a mean value of 226.7 ± 45.9 per 1 mm² of tissue, while in the control group, it was only 68.3 ± 17.2 per 1 mm² of tissue. With the application of only Mucoderm, it was 131.7 ± 37.1 per 1 mm² of tissue, and with only the pCMV-VEGF165 plasmid, it was 145 ± 37.82 per 1 mm² of the sample. Thus, the use of the pCMV-VEGF165 plasmid (‘Neovasculgen’) in combination with the xenogeneic collagen matrix Mucoderm potentiated the pro-proliferative effect of the membrane and the pro-vascularization effect of the plasmid. These results indicate the promising potential of this innovative approach for clinical applications in regenerative medicine and dentistry. Full article

Background: Hypersensitivity to the new dermal injectable porcine-based collagen with lidocaine featuring a novel cross-linking technology (test filler) for nasolabial fold correction was compared to the commercially available traditional cross-linked dermal injectable porcine-based collagen with lidocaine (control filler). Methods: Recruited participants (n = 279) received a single 0.1 mL intradermal injection of either test filler or control filler in the left forearm as a screening skin allergy test. Injection sites were assessed clinically at 24 h post-implant. Treatment was given to 252 successfully screened participants, and injection sites were monitored for 21 days. Immunological examinations were performed at screening and then at 4 and 24 weeks post-treatment. Observations for adverse events continued until the 52nd week. Results: Intradermal allergy testing results were negative for all the test recipients (0/124) and positive for two control recipients (2/132, 1.5%). Most of the participants exhibited no changes in serum immunoglobulin (IgG, IgM) and complement (C3, C4) levels. No serious adverse events related to the device were recorded. Most adverse events were common complications of dermal filler treatment and were related to the injection site. Most adverse effects were resolved or under control by 52 weeks. Conclusions: Hypersensitivity reactions with the test filler were lower than those with the control filler, validating the safe use of test filler for nasolabial fold correction without the need for pretreatment skin testing. Full article

Cold atmospheric plasma devices generate reactive oxygen and nitrogen species that can be anti-microbial but also promote cell migration, differentiation, and tissue wound healing. This report investigates the healing of surgical incisions created using cold plasma generated by the J-Plasma scalpel (Precise Open handpiece, Apyx Medical, Inc.) compared to a steel scalpel in in vivo porcine and rat models. The J-Plasma scalpel is currently FDA approved for the delivery of helium plasma to cut, coagulate, and ablate soft tissue during surgical procedures. To our knowledge, this device has not been studied in creating surgical incisions but only during deeper dissection and hemostasis. External macroscopic and histologic grading by blinded reviewers revealed no significant difference in wound healing appearance or physiology in incisions created using the plasma scalpel as compared with a steel blade scalpel. Incisions created with the plasma scalpel also had superior hemostasis and a reduction in tissue and blood carryover. Scanning electron microscopy (SEM) and histology showed collagen fibril fusion occurred as the plasma scalpel incised through the tissue, contributing to a sealing effect. In addition, when bacteria were injected into the dermis before incision, the plasma scalpel disrupted the bacterial membrane as visualized in SEM images. External macroscopic and histologic grading by blinded reviewers revealed no significant difference in wound healing appearance or physiology. Based on these results, we propose additional studies to clinically evaluate the use of cold plasma in applications requiring hemostasis or when an increased likelihood of subdermal pathogen leakage could cause surgical site infection (i.e., sites with increased hair follicles). Full article

Morton’s neuroma (MN) is a compressive neuropathy of the common plantar digital nerve, most commonly affecting the third inter-digital space. The conservative approach is the first recommended treatment option. However, other different approaches have been proposed, offering several options of treatments, where, several degrees of efficacy and safety have been reported. We treated five consecutive patients affected by MN through three indirect ultrasound-guided injections of type I porcine collagen at weekly intervals. All patients were assessed before the treatment, after the treatment and up to 6 months after the last injection via AOFAS and VNS scores for pain, in which the function and pain were evaluated, respectively. In all patients, both analyzed variables progressively ameliorated, with benefits lasting until the last follow-up. The trend of the scores during the follow-up showed significant statistical differences. No side effects occurred. To our knowledge, this is the first study on injections of type I porcine collagen for the treatment of Morton’s neuroma. Future research is needed to confirm the positive trend achieved in this MN mini-series. Full article

Wound healing is a complex process involving cell proliferation, migration, and extracellular matrix (ECM) remodeling. Extracellular vesicles (EVs) or exosomes derived from adipose tissue-derived stem cells (ASCs) are emerging as promising alternatives to cell therapy for advanced wound healing. Hyaluronic acid (HA), a major component of the skin ECM, is widely utilized in wound dressings and dermal fillers. This study aimed to investigate the effects of ASC-derived exosomes (ASC-EXOs) on human dermal fibroblasts (HDFs) and their potential combination with HA in in vivo wound healing and dermal filler models. In HDFs, ASC-EXOs increased cell proliferation and migration. ASC-EXOs also upregulated the expression of genes involved in cell proliferation and wound healing while stimulating collagen production in HDFs. In a porcine wound healing model, topical treatment with a combination of HA and ASC-EXOs led to higher wound closure rates compared to HA alone. Histological examination showed increased re-epithelialization and collagen type III deposition in wounds treated with the combination of HA and ASC-EXOs. In a mouse dermal filler model, tissues injected with the combination of HA and ASC-EXOs exhibited thicker tissue layers, increased vascularization, enhanced infiltration of myofibroblasts, and higher levels of collagen III and collagen fiber content compared to HA alone. These findings suggest that ASC-EXOs have beneficial effects on cell proliferation, migration, and gene expression related to wound healing, and they may accelerate wound closure and promote tissue regeneration. Furthermore, the combination of HA and ASC-EXOs may enhance wound healing and tissue remodeling, indicating its potential for both clinical and regenerative aesthetic applications in skin repair and regeneration. Full article

Gastroesophageal reflux disease (GERD) has been growing globally, with an increasing burden on the healthcare system due to multiple factors, such as aging and obesity. The current study evaluated the feasibility of endoscopic balloon-assisted laser treatment (EBLT) in a porcine model. GERD was initially developed in three animals via botulinum toxin injection into lower esophageal sphincter (LES). A week after the injection, the EBLT was performed on the GERD-developed models (control = 1 vs. treated = 2). A dose of 30 W of 980 nm laser light was endoscopically applied for 90 s to the LES. Both endoscopic ultrasound and manometry were performed before and after the EBLT. After 12 weeks, esophageal tissues were extracted and prepared for histological analysis. The maximum mucosa temperature was below 50 °C during the EBLT. Compared to control, the treated group yielded thicker and shorter LES muscle layers and maintained LES pressure. Through histology, the EBLT reinforced the muscularis layer with preserved mucosa and mild remodeling of the intermuscular collagen in the LES. The current study demonstrated the feasibility of EBLT as a new endoscopic approach for GERD. Further studies will examine the EBLT in a larger number of animals to warrant efficacy and safety for clinical translations Full article

Maintaining periodontal and peri-implant soft tissues health is crucial for the long-term health of teeth and dental implants. New biomedical strategies aimed at avoiding connective tissue alterations and related diseases (e.g., periodontitis and peri-implantitis) are constantly evolving. Among these, collagen-based medical products have proven to be safe and effective. Accordingly, the aim of the present study was to evaluate the effects of Dental SKIN BioRegulation (Guna S.p.a., Milan, Italy), a new injectable medical device composed of type I collagen of porcine origin, on primary cultures of human gingival fibroblasts (hGF). To this end, hGF were cultured on collagen-coated (COL, 100 µg/2 mL) or uncoated plates (CTRL) before evaluating cell viability (24 h, 48 h, 72 h, and 7 d), wound healing properties (3 h, 6 h, 12 h, 24 h, and 48 h), and the activation of mechanotransduction markers, such as FAK, YAP, and TAZ (48 h). The results proved a significant increase in cell viability at 48 h (p < 0.05) and wound closure at 24 h (p < 0.001) of hGF grown on COL, with an increasing trend at all time-points. Furthermore, COL significantly induced the expression of FAK and YAP/TAZ (p < 0.05), thereby promoting the activation of mechanotransduction signaling pathways. Overall, these data suggest that COL, acting as a mechanical bio-scaffold, could represent a useful treatment for gingival rejuvenation and may possibly help in the resolution of oral pathologies. Full article

Lower back pain commonly arises from intervertebral disc (IVD) failure, often caused by deteriorating annulus fibrosus (AF) and/or nucleus pulposus (NP) tissue. High socioeconomic cost, quality of life issues, and unsatisfactory surgical options motivate the rapid development of non-invasive, regenerative repair strategies for lower back pain. This study aims to evaluate the AF regenerative capacity of injectable matrix repair strategy in ex vivo porcine organ culturing using collagen type-I and polycaprolactone nanofibers (PNCOL) with encapsulated fibroblast cells. Upon 14 days organ culturing, the porcine IVDs were assessed using gross optical imaging, magnetic resonance imaging (MRI), histological analysis, and Reverse Transcriptase quantitative PCR (RT-qPCR) to determine the regenerative capabilities of the PNCOL matrix at the AF injury. PNCOL-treated AF defects demonstrated a full recovery with increased gene expressions of AF extracellular matrix markers, including Collagen-I, Aggrecan, Scleraxis, and Tenascin, along with anti-inflammatory markers such as CD206 and IL10. The PNCOL treatment effectively regenerates the AF tissue at the injury site contributing to decreased herniation risk and improved surgical outcomes, thus providing effective non-invasive strategies for treating IVD injuries. Full article

Inflammation and stiffness in the arteries is referred to as vascular calcification. This process is a prevalent yet poorly understood consequence of cardiovascular disease and diabetes mellitus, comorbidities with few treatments clinically available. Because this is an active process similar to bone formation, it is hypothesized that osteoclasts (OCs), bone-resorbing cells in the body, could potentially work to reverse existing calcification by resorbing bone material. The receptor activator of nuclear kappa B-ligand (RANKL) is a molecule responsible for triggering a response in monocytes and macrophages that allows them to differentiate into functional OCs. In this study, OC and RANKL delivery were employed to determine whether calcification could be attenuated. OCs were either delivered via direct injection, collagen/alginate microbeads, or collagen gel application, while RANKL was delivered via injection, through either a porcine subdermal model or aortic injury model. While in vitro results yielded a decrease in calcification using OC therapy, in vivo delivery mechanisms did not provide control or regulation to keep cells localized long enough to induce calcification reduction. However, these results do provide context and direction for the future of OC therapy, revealing necessary steps for this treatment to effectively reduce calcification in vivo. The discrepancy between in vivo and in vitro success for OC therapy points to the need for a more stable and time-controlled delivery mechanism that will allow OCs not only to remain at the site of calcification, but also to be regulated so that they are healthy and functioning normally when introduced to diseased tissue. Full article