Regenerative Medicine in Animal Wound Healing and Musculoskeletal Disorders

A special issue of Animals (ISSN 2076-2615). This special issue belongs to the section "Veterinary Clinical Studies".

Deadline for manuscript submissions: closed (31 July 2023) | Viewed by 8543

Special Issue Editors


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Guest Editor
Departamento de Medicina y Cirugía Animal, Facultad de Veterinaria, Universidad Cardenal Herre-ra-CEU, CEU Universities, 46115 Valencia, Spain
Interests: orthopedics; general surgery; regenerative therapies; arthroscopic surgery

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Guest Editor Assistant
Bioregenerative Medicine and Applied Surgery Research Group, Department of Animal Medicine and Surgery, University CEU—Cardenal Herrera, CEU Universities, C/Tirant lo Blanc, 7, Alfara del Patriarca, 46115 Valencia, Spain
Interests: bioregenerative therapies; biomaterials; stem cells; platelet concentrates; osteoarthritis; orthopedics

Special Issue Information

Dear Colleagues,

During the last decade, regenerative therapies, especially stem cells and platelets concentrates, have drawn the attention of both veterinary clinicians and researchers. These cells and cell-free therapies seem to have potential to regenerate all types of animal tissue, and thus, their use has been indicated in the treatment of several conditions, including corneal ulcers, soft tissue damage, chronic and complicated wound healing, and orthopedic pathologies such as osteoarthritis. Currently, significant effort is being dedicated to widening their application scope in veterinary practice.

The aim of this Special Issue is to document evidence-based approaches to the use of these bioregenerative therapies in the clinical management of several diseases in companion animals, with particular emphasis on, but not limited to, orthopedic pathologies and wound healing.

In this Special Issue, original research articles and reviews are welcomed.

Prof. Dr. José María Carrillo
Guest Editor

Marta Torres-Torrillas
Guest Editor Assistant

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Keywords

  • platelet-rich plasma
  • stem cells
  • bioregenerative therapies
  • biomaterials
  • orthopedics
  • wound healing

Published Papers (6 papers)

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Research

15 pages, 3253 KiB  
Article
Structural Features of Connective Tissue Formed around Resin Implants Subcutaneously Embedded in Dairy Cows
by Yuka Katayama, Osamu Ichii, Teppei Nakamura, Keita Yanase, Masaya Hiraishi, Takashi Namba, Yuki Otani, Teppei Ikeda, Erika Tsuji, Natsuko Tsuzuki, Ken Kobayashi, Yasuhiro Kon and Takanori Nishimura
Animals 2023, 13(23), 3700; https://doi.org/10.3390/ani13233700 - 29 Nov 2023
Viewed by 807
Abstract
Foreign body reactions (FBRs) are inadvertently observed in invading or artificially embedded materials, triggering inflammation and subsequent fibrotic processes to occur in situ. Here, we assessed the spatiotemporal formation of connective tissue around implanted materials to establish a technique using connective tissue formed [...] Read more.
Foreign body reactions (FBRs) are inadvertently observed in invading or artificially embedded materials, triggering inflammation and subsequent fibrotic processes to occur in situ. Here, we assessed the spatiotemporal formation of connective tissue around implanted materials to establish a technique using connective tissue formed by FBRs as xenografts. An acrylic resin implant, comprising a columnar inner rod and a tubular outer cylinder (OC) with several slits, was embedded in adult dairy cows. Tissues formed in the inner rod and OC groups were histologically analyzed at weeks 2, 4, 8, and 12. Edematous tissues with non-collagenous fibers formed for 2 weeks and showed increased cellularity after 4 weeks. The weight, thickness, amounts of total protein, collagen, DNA, and quantitative scores of α-smooth muscle actin-positive myofibroblasts or elastic fibers notably increased after 8 weeks, with condensed collagen fibers showing orientation. Inflammatory cells were primarily localized in tissues close to the OC, and their numbers increased, with the count of CD204+ cells peaking at 8 weeks and declining at 12 weeks. The count of Ki67+ proliferating cells slightly increased in tissues close to the OC; however, the number and lumen of CD31+ vessels increased. These results may help understand FBR-related tissue remodeling. Full article
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18 pages, 6753 KiB  
Article
The Use of Stromal Vascular Fraction in Long Bone Defect Healing in Sheep
by Elena I. Pappa, Mariana S. Barbagianni, Stefanos G. Georgiou, Labrini V. Athanasiou, Dimitra Psalla, Dionysios Vekios, Eleni I. Katsarou, Natalia G. C. Vasileiou, Pagona G. Gouletsou, Apostolos D. Galatos, Nikitas N. Prassinos, Dimitris A. Gougoulis, Marianna Angelidou, Vicky Tsioli, George C. Fthenakis and Aikaterini I. Sideri
Animals 2023, 13(18), 2871; https://doi.org/10.3390/ani13182871 - 09 Sep 2023
Cited by 1 | Viewed by 1016
Abstract
The objectives of the present study were to evaluate (a) the feasibility of using stromal vascular fraction (SVF) and nanocrystalline hydroxyapatite (nHA) paste in combination for the treatment of segmental bone defect, (b) the quality of the callus produced, (c) the potential improvement [...] Read more.
The objectives of the present study were to evaluate (a) the feasibility of using stromal vascular fraction (SVF) and nanocrystalline hydroxyapatite (nHA) paste in combination for the treatment of segmental bone defect, (b) the quality of the callus produced, (c) the potential improvement of the autograft technique, and (d) the direct comparison of the biomaterial to the use of autogenous cancellous bone. Unilateral, segmental mid-diaphyseal bone defect was created on the right metatarsus of skeletally mature sheep animals (n = 24) under anesthesia (D0). Residual segments were stabilized by stainless-steel plates and appropriate screws. Defects were managed as follows: group A: use of nHA paste to filling, group B: use of autogenous bone graft mixed with nHA bone paste, placed in defect, group C: use of SVF mixed with nHA bone paste injected into defect, group D: use of bone graft and SVF with nHA paste before apposition in bone defect. SVF had been previously isolated from adipose tissue of the animals intra-operatively after digestion with collagenase solution and neutralization. Animals were evaluated clinically and by X-raying and ultrasonographic examination of the defect, at regular intervals, until D90. Ultrasonographic assessment performed along the length of the defect included calculation of the length of the bone defect and assessment of vascularization. SVF was successfully isolated from group C and D animals, with the average yield being 1.77 × 106 cells. The comparison of clinical scores (based on the ‘Kaler scale’) on each post-operative day indicated significant differences between the four groups on D1 to D30 (p < 0.01); the median clinical score within group A was 2.5 for D1-D30 and 1 for the entire period; respective scores for other groups were 1.5 (p = 0.07) and 0 (p = 0.033). Differences in radiographic assessment scores were significant for scores obtained on D60 (p = 0.049) and D90 (p = 0.006). There was a significant difference between the four groups in the length of the bone defect, as assessed ultrasonographically, for the entire length of the study; median values were 8, 8.5, 6, and 8 mm for groups A, B, C, and D, respectively (p = 0.008). There was a significance in the differences between median scores obtained during the histopathological examination: 2, 11, 13.5, and 12 for group A, B, C, and D (p = 0.022). There was an inverse correlation between the overall scores of histopathological evaluations and the length of the bone defect (observed on D90) (p < 0.0001) and a correlation between the overall scores and the radiographic assessment scores (obtained on D90) (p < 0.0001). This is the first study in which the efficacy of fresh autologous Stromal Vascular Fraction (SVF) from adipose tissue in enhancing bone healing in a long, weight-bearing, diaphyseal bone was evaluated. It is concluded that the lumbosacral region was an attractive site for harvesting adipose tissue, the use of SVF contributed to faster rehabilitation post-operatively, and SVF significantly enhanced bone formation; in general, the results indicated an osteogenic potential of SVF comparable to the gold standard autologous bone graft. Full article
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14 pages, 14038 KiB  
Article
Clinical Evaluation of Medical Ozone Use in Domestic Feline Cutaneous Wounds—A Short Case Series
by Nicuşor-Valentin Oros, Călin Repciuc, Ciprian Ober, Cosmin Peștean, Mircea Valerian Mircean and Liviu-Ioan Oana
Animals 2023, 13(17), 2796; https://doi.org/10.3390/ani13172796 - 02 Sep 2023
Viewed by 1410
Abstract
Support and management of second-intention wound healing involves frequent dressing changes having different properties. Dressings can range from simple ones, such as nonadherent dressings, to more complex options, such as foam, hydrocolloid, alginate or negative pressure dressings. Seven cats were enrolled in the [...] Read more.
Support and management of second-intention wound healing involves frequent dressing changes having different properties. Dressings can range from simple ones, such as nonadherent dressings, to more complex options, such as foam, hydrocolloid, alginate or negative pressure dressings. Seven cats were enrolled in the study with a total of nine wounds of various sizes with different etiology sizes and localizations. Three methods of local ozone administration were used to cover more of the ozone properties in the treatment of wounds: bagging, perilesional subcutaneous infiltrations and lavages with ozonated saline. Evaluation of the healing process was performed by clinical observation and wound area measurements every seven days until the complete recovery of the patients. The results of this study should encourage clinicians to consider medical ozone as a new therapeutic approach with regenerative properties in the second-intention healing of cats presenting cutaneous wounds. Full article
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17 pages, 3685 KiB  
Article
Titanium Dioxide Nano-Formulation: Characterization, Antimicrobial Activity, and Wound Healing in Animals
by Noppason Pangprasit, Yada Thammawong, Alongkorn Kulsirorat, Phongsakorn Chuammitri, Aphisek Kongkaew, Montira Intanon, Witaya Suriyasathaporn, Surachai Pikulkaew and Wasana Chaisri
Animals 2023, 13(17), 2688; https://doi.org/10.3390/ani13172688 - 22 Aug 2023
Cited by 1 | Viewed by 998
Abstract
The use of metal oxide nanoparticles as an alternative antimicrobial agent has gained attention due to the increasing problem of antimicrobial resistance. Understanding its properties and potential benefits can contribute to the development of more effective and sustainable treatments in veterinary medicine. The [...] Read more.
The use of metal oxide nanoparticles as an alternative antimicrobial agent has gained attention due to the increasing problem of antimicrobial resistance. Understanding its properties and potential benefits can contribute to the development of more effective and sustainable treatments in veterinary medicine. The aim of this study was to characterize TiO2-NP formulations and evaluate their antibacterial and wound healing abilities. The diameters and zeta potentials were determined using the Zetasizer in conjunction with dynamic light scattering. The agar-well diffusion method, time-kill kinetic assay and crystal violet assay were used to evaluate their antimicrobial activities. Wound healing assays were conducted both in vitro and in vivo. The study demonstrated that TiO2-NP formulations exhibit significant antimicrobial properties against various bacterial strains such as S. aureus and E. coli. No measurable E. coli growth was observed within a 15-min period following exposure to TiO2-NP formulations. The TiO2-NP formation can improve wound healing by enhancing cell migration and collagen formation in both in vitro and in vivo conditions. In summary, our study suggests that TiO2-NP has the potential for use as an antimicrobial agent for animal wound treatment due to its ability to suppress bacterial growth and biofilm formation, as well as to enhance wound healing. Full article
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12 pages, 2560 KiB  
Article
Platelet- Rich Plasma Treatment Supported by Ultrasound Detection of Septa in Recurrent Canine Aural Hematoma: A Case Series
by Paola Palagiano, Lisa Graziano, Walter Scarabello, Priscilla Berni, Valentina Andreoli and Stefano Grolli
Animals 2023, 13(15), 2456; https://doi.org/10.3390/ani13152456 - 29 Jul 2023
Cited by 1 | Viewed by 1368
Abstract
Aural hematoma is a common pathological condition in veterinary practice with a high incidence rate in dogs. Drainage, corticosteroid injections, and surgical approaches represent the common treatments in these clinical cases. However, surgery leaves visible signs and is usually correlated with recurrence, scars, [...] Read more.
Aural hematoma is a common pathological condition in veterinary practice with a high incidence rate in dogs. Drainage, corticosteroid injections, and surgical approaches represent the common treatments in these clinical cases. However, surgery leaves visible signs and is usually correlated with recurrence, scars, and deformation of the treated pinna. For this reason, more effective and less invasive methods have been proposed over the years. Platelet-Rich Plasma (PRP) is one of the most promising options due to its pro-regenerative properties and capability to modulate the inflammatory state. The present work reports 12 cases of canine aural hematoma treated with PRP. The PRP treatment was combined with an ultrasound evaluation of the pinna to detect and treat all involved septa. The results show that relatively large volumes (2 mL) of PRP associated with an ultrasound guide are safe and efficacious in the treatment of canine aural hematoma requiring a maximum of two infiltrations, both in acute and chronic conditions. All the patients recovered their normal ear thickness (compared with the controlateral one) without relapses, averaging 38.5 days from their first treatment (10–90 days; SD: 24.7). The key role of PRP combined with a tailored diagnosis process carried out by the veterinarian, which included using an ultrasound system and the proper bandage, suggests that this approach may represent a valid alternative to surgery and corticosteroids. Full article
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14 pages, 2730 KiB  
Article
In Vitro Anti-Inflammatory and Regenerative Effects of Autologous Conditioned Serum from Dogs with Osteoarthritis
by Sirikul Soontararak, Piyathida Ardaum, Napaporn Senarat, Sarawut Yangtara, Chalermpol Lekcharoensuk, Iyarath Putchong, Narudee Kashemsant, Monchanok Vijarnsorn, Lyndah Chow, Steven Dow and Porntippa Lekcharoensuk
Animals 2022, 12(19), 2717; https://doi.org/10.3390/ani12192717 - 10 Oct 2022
Cited by 3 | Viewed by 2266
Abstract
Osteoarthritis (OA) is mostly incurable and non-regenerative with long-term complications. Autologous conditioned serum (ACS), which is enriched in Interleukin 1 receptor antagonists (IL-1RA) and growth factors, could be an alternative treatment to accelerate the positive therapeutic effects. ACS is proposed to alleviate inflammation [...] Read more.
Osteoarthritis (OA) is mostly incurable and non-regenerative with long-term complications. Autologous conditioned serum (ACS), which is enriched in Interleukin 1 receptor antagonists (IL-1RA) and growth factors, could be an alternative treatment to accelerate the positive therapeutic effects. ACS is proposed to alleviate inflammation by blocking IL-1 receptors. However, to date, there is no report focusing on the cell-mediated anti-inflammation and regenerative effect caused by ACS, especially the ACS from patients. Therefore, this study aims to investigate the therapeutic potential of ACS generated from dogs with spontaneous OA, focusing on its promising anti-inflammatory and regenerative properties in vitro compared to the matched plasma. We found that ACS prepared from ten OA dogs contained significant concentrations of IL-1RA, vascular endothelial growth factor, and transforming growth factor beta, which are key cytokines in anti-inflammation and angiogenesis. Furthermore, we found that ACS suppressed T cell activity by reducing proliferation of effector T cells and simultaneously expanding numbers of immune suppressive FOXP3+ T cells. Lastly, we showed that ACS enhanced the proliferation of osteocytes and fibroblasts and promoted extracellular matrix gene expression in primary chondrocyte culture. Therefore, these studies indicate that ACS prepared from dogs with OA is active as an immunomodulatory and regenerative strategy for use in OA management. Full article
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