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Molecular Injection Therapy in Orthopedic and Musculoskeletal Disorders: Conservative Approaches and Innovative Treatments

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Orthopedics".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 4672

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Special Issue Editors

Dr. Niccola Funel

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Guest Editor

Department of Laboratory Diagnostics, Division of Immunohematology, Section of Laboratory Analysis, Azienda Ospedaliera USL Nordovest, Via Lippi Francesconi, 556-55100 Lucca, Italy
Interests: molecular therapy; nucleic acids; tendinitis; statistics; analytical data management
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Prof. Dr. Paolo Domenico Parchi

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Orthopedic and Traumatology, University-Hospital of Pisa, University of Pisa, 56126 Pisa, Italy
Interests: traumatology; articular disorders; tendinitis; rehabilitation; conservative treatment
Special Issues, Collections and Topics in MDPI journals

Dr. Andrea del Chiaro

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Guest Editor Assistant

Department of Surgery, Division of Ortopedics, Azienda Ospedaliera USL Nordovest, Via Lippi Francesconi, 556-55100 Lucca, Italy
Interests: shoulder pathologies; injection therapy; rehabilitation; conservative approach

Special Issue Information

Dear Colleagues,

It is a great pleasure to present the following Special Issue in this journal: “Molecular Injection Therapy in Orthopedic and Musculoskeletal Disorders: Conservative Approaches and Innovative Treatments”, inside the orthopedic field. As we know, chronic pain and traumatic injuries in musculoskeletal disorders represent a significant and widespread health problem. These health difficulties affect people of all ages, negatively impacting the quality of life from a social, economic, and (not least) health point of view. In some cases, various surgical treatments are unavoidable and lead to various problems. When the clinical-surgical approach is deferrable towards physiotherapy, this has played a crucial role in improving the physio-psycho-social conditions of orthopedic patients. Nevertheless, therapies based on emerging minimally invasive approaches, including infiltrations of drugs, substances, or medical devices, are showing promising results in pain management, improving functionality, and accelerating recovery. Among these, hyaluronic acid, collagen, polynucleotides, platelet-rich plasma, and corticosteroids certainly stand out. These procedures can often be assisted by ultrasound imaging in order to increase the loco-regional positioning of the treatment. In the orthopedic field, there is already evidence that demonstrates the use of these combinations in conservative clinical decisions as a valid therapeutic alternative for musculoskeletal disorders.

This Special Issue aims to illustrate to the readers the updated evidence (also clinical experimental) and their consequent conservative clinical approach to the diagnosis and treatment of musculoskeletal disorders. This new evidence will be useful to raise awareness of the application of an appropriate conservative treatment. Original articles, systematic reviews, or meta-analyses are welcome.

We look forward to your contributions.

Dr. Niccola Funel
Prof. Dr. Paolo Domenico Parchi
Guest Editors

Dr. Andrea del Chiaro
Guest Editor Assistant

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Keywords

injection therapy
conservative approaches
medical devices
collagen
polyribonucleotide
plasma-rich platelets
hyaluronic acids
anti-inflammatory therapy
tendinitis, osteoarthritis, musculoskeletal disorder, pain reduction
regenerative medicine
new clinical approaches
physiotherapy
comparative studies: surgery vs. conservative approaches

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Published Papers (5 papers)

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13 pages, 2597 KB

Open AccessArticle

Influence of Tendon Location on the Clinical Response to Platelet-Rich Plasma: A Prospective Cohort Study of Rotator Cuff, Achilles and Patellar Tendinopathies

by Mikel Sánchez, David Santos-Hernández, Cristina Jorquera, Jaime Oraa, Renato Andrade, João Espregueira-Mendes, Fernando Yangüela, Sergio González, Jorge Guadilla and Diego Delgado

J. Clin. Med. 2026, 15(5), 2005; https://doi.org/10.3390/jcm15052005 - 5 Mar 2026

Viewed by 501

Abstract

Background/Objectives: Platelet-rich plasma (PRP) has become a therapeutic option for tendinopathies. Its clinical efficacy depends on several factors, including the target tendon. The aim of this study was to evaluate the PRP efficacy for tendinopathies in the rotator cuff (RC), Achilles tendon (AT), and patellar tendon (PT). Methods: We conducted a prospective cohort study including patients with RC, AT and PT tendinopathies. Each patient received three multitarget PRP (intratendinous and peritendinous) treatments at intervals of two weeks. Clinical outcomes were assessed at baseline and 6 months using tendon-specific scores (DASH for RC, VISA-A for AT and VISA-P for PT). Responders were identified based on the Minimal Clinically Important Improvement (MCII). Comparative statistical tests and multivariate regression were performed for the analysis. Results: A total of 49 patients were included (RC: 15, AT: 18, PT: 16). The number of responders at 6 months was 33 (67.4%), with 11 (73.3%) in the RC Group, 14 (75.0%) in the AT Group and 8 (50.0%) in the PT Group. The RC and AT patients experienced a significant improvement according to their scores (p < 0.001), which was not seen in the PT group (p = 0.065). The percentage of responders was higher in women (12/13, 92.3%) than men (21/36, 58.3%) (p = 0.025). Conclusions: Repeated intratendinous and peritendinous PRP injections in RC, AT, and PT tendinopathy improved joint-related function six months after treatment. This improvement was less pronounced in patients with PT and the proportion of responders was higher among women. Full article

(This article belongs to the Special Issue Molecular Injection Therapy in Orthopedic and Musculoskeletal Disorders: Conservative Approaches and Innovative Treatments)

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13 pages, 1568 KB

Open AccessArticle

Clinical Outcomes of Injectable Porcine Collagen in Diabetic Patients with Achilles Tendinopathy: A Retrospective Study

by Giacomo Placella, Niccolò Biavardi, Mattia Alessio Mazzola and Vincenzo Salini

J. Clin. Med. 2026, 15(4), 1381; https://doi.org/10.3390/jcm15041381 - 10 Feb 2026

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Abstract

Background/Objective: Achilles tendinopathy (AT) is a disabling condition, and treatment options are limited in patients in whom corticosteroid injections are discouraged or contraindicated, including individuals with diabetes. Porcine collagen injections have been proposed as a conservative option; however, clinical evidence in diabetic populations remains limited. This study aims to describe pain and functional outcomes after peritendinous collagen injections in diabetic patients with chronic Achilles tendinopathy. Methods: Twenty-two diabetic patients with ultrasound-confirmed degenerative Achilles tendinopathy refractory to conservative management were retrospectively included and split into two groups according to AT type: insertional (IAT) and non-insertional/midportion (NIAT). All patients received five weekly ultrasound-guided peritendinous collagen injections. Outcomes included VAS assessed at baseline, after the second injection, at 1 month, and at 6 months; VISA-A at baseline and 6 months; return-to-work (RTW) time; and adverse events. Baseline variables included BMI, HbA1c, symptom duration, and previous treatments. Analyses were based on descriptive statistics and within-group comparisons over time. Results: All patients completed the treatment protocol, and no adverse events were recorded. Pain significantly improved over follow-up in both subgroups. Mean VAS decreased from baseline to 6 months (mean ΔVAS: 5.1 in IAT and 4.4 in NIAT; p = 0.001 for within-group change). VISA-A also improved at 6 months (mean ΔVISA-A: 32.78 in IAT and 38.97 in NIAT; p < 0.0001). Median RTW was 37 days in IAT and 35 days in NIAT (p > 0.05). No significant between-group differences were observed for VAS or VISA-A changes (p > 0.05). Conclusions: In this uncontrolled retrospective case series, peritendinous collagen injections were feasible and well-tolerated in diabetic patients with Achilles tendinopathy and were associated with clinically relevant improvements in pain and functional outcomes at 6 months. These findings are hypothesis-generating and warrant confirmation in prospective controlled studies. Full article

(This article belongs to the Special Issue Molecular Injection Therapy in Orthopedic and Musculoskeletal Disorders: Conservative Approaches and Innovative Treatments)

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25 pages, 2638 KB

Open AccessArticle

Toward Personalized ACS Therapy: How Disease Status and Patient Lifestyle Shape the Molecular Signature of Autologous Conditioned Serum

by Christoph Bauer, Daniela Kern, Kalojan Petkin and Stefan Nehrer

J. Clin. Med. 2026, 15(3), 1014; https://doi.org/10.3390/jcm15031014 - 27 Jan 2026

Viewed by 353

Abstract

Background/Objectives: Autologous conditioned serum (ACS) is an intra-articular orthobiologic for osteoarthritis (OA) intended to shift the joint cytokine milieu toward an anti-inflammatory, pro-regenerative profile. In the present study, we compared the molecular composition of ACS (specifically IMPACT^® ACS) from OA patients with that of healthy controls and assessed demographic and lifestyle influences on mediator levels. Methods: ACS was prepared from the whole blood of 50 OA patients and 20 healthy controls using the IMPACT^® centrifugation system (Plasmaconcept, Cologne, Germany) with glass-bead incubation and standardized handling. Cytokines, growth factors, and matrix metalloproteinases (MMPs) were quantified using multiplex immunoassays and ELISA. To account for demographic imbalances across cohorts, the primary findings were verified using age- and sex-adjusted multiple linear regression models. Results: Pro-inflammatory mediators were minimal in both cohorts, with IL-1β undetectable and IL-6 and TNF-α at very low levels. IL-1 receptor antagonist (IL-1RA) was consistently present. Notably, OA-derived ACS exhibited a catabolic shift compared to controls, characterized by significantly higher MMP-2 and MMP-3 levels. Growth factor profiling showed lower TGF-β1 and TGF-β3 in OA-derived ACS, with TGF-β2 showing no significant difference after adjustment. Exploratory stratified analyses indicated potential differences across sex, BMI, smoking status, and diet for select mediators, though subgroup sizes were limited. Conclusions: ACS prepared with a standardized IMPACT^® protocol displays a broad anti-inflammatory profile. However, increased MMPs and isoform-specific differences in TGF-β reflect a disease-associated molecular imprint. Consequently, patient-related heterogeneity supports the need for standardized reporting and motivates further research into stratified ACS therapy. Full article

(This article belongs to the Special Issue Molecular Injection Therapy in Orthopedic and Musculoskeletal Disorders: Conservative Approaches and Innovative Treatments)

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18 pages, 1621 KB

Open AccessArticle

Plasma Rich in Growth Factors (PRGF) Versus Saline Intraosseous Infiltrations Combined with Intra-Articular PRGF in Severe Knee Osteoarthritis: A Prospective Double-Blind Multicentric Randomized Controlled Trial with 1-Year Follow-Up

by Mónica Sánchez Santiuste, Víctor Vaquerizo García, José Antonio Pareja Esteban, Roberto Prado, Sabino Padilla and Eduardo Anitua

J. Clin. Med. 2025, 14(22), 8075; https://doi.org/10.3390/jcm14228075 - 14 Nov 2025

Cited by 3 | Viewed by 1014

Abstract

Background/Objectives: Severe knee osteoarthritis (KOA) is a degenerative disease that significantly affects quality of life (QoL). Although intra-articular (IA) injections of plasma rich in growth factors (PRGF) have proven effective, the subchondral bone plays a crucial role in pathogenesis. The objective of this study was to evaluate the efficacy of intraosseous (IO) PRGF infiltrations in comparison with a saline placebo, followed by the conventional standard treatment of three IA PRGF injections, in enhancing clinical outcomes in patients suffering from severe KOA. Methods: A prospective, randomized, double-blind, multicenter clinical trial was conducted. Eighty-six patients with Kellgren–Lawrence grade III-IV KOA were randomly assigned to two groups: one received an IO infiltration of PRGF and the other received an IO saline solution. Both groups subsequently received three IA PRGF injections. Clinical outcomes were assessed using the KOOS and WOMAC scales at baseline and at 3, 6, and 12 months. Results: Both groups showed a statistically significant improvement in all KOOS and WOMAC subscales at all follow-up points compared to their baseline values. However, the group that received the IO PRGF infiltration demonstrated significantly greater improvements in nearly all domains of the KOOS and WOMAC scales (pain, symptoms, function, and quality of life) at 3, 6, and 12 months compared to the saline group (p < 0.05). No serious adverse events were recorded. Conclusions: The combination of intraosseous and intra-articular PRGF infiltrations is a superior therapeutic strategy to the combination of intraosseous saline solution and intra-articular PRGF for treating severe KOA. These findings suggest that treating the subchondral bone directly with PRGF has a significant and clinically relevant therapeutic effect, resulting in greater pain reduction and functional improvement at one-year follow-up. Full article

(This article belongs to the Special Issue Molecular Injection Therapy in Orthopedic and Musculoskeletal Disorders: Conservative Approaches and Innovative Treatments)

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23 pages, 4540 KB

Open AccessBrief Report

Injectable Porcine Collagen in Musculoskeletal Disorders: A Delphi Consensus

by Orazio De Lucia, Federico Giarda, Andrea Bernetti, Chiara Ceccarelli, Giulia Letizia Mauro, Fabrizio Gervasoni, Lisa Berti and Antonio Robecchi Majnardi

J. Clin. Med. 2025, 14(17), 6058; https://doi.org/10.3390/jcm14176058 - 27 Aug 2025

Cited by 2 | Viewed by 2025

Abstract

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

(This article belongs to the Special Issue Molecular Injection Therapy in Orthopedic and Musculoskeletal Disorders: Conservative Approaches and Innovative Treatments)

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