Tissue Healing Process Research Articles

Platelet-rich plasma (PRP) accelerates murine patellar tendon healing through enhancement of angiogenesis and collagen synthesis

PurposeAlthough platelet-rich plasma (PRP) therapy has become an increasingly popular treatment for sports-related injuries, the molecular mechanisms of PRP on tissue healing process remain poorly understood. The aim of the present study was to develop an experimental method quantifying the efficacy of PRP with murine patellar tendon injury model, leading to future elucidation of the mechanisms of PRP on healing processes.MethodsFull-thickness defects were created in the central third of the murine patellar tendon. The prepared allogenic PRP gel was applied on the defect of the patellar tendon (PRP group), while the remaining mice served as the untreated control group. Mice were sacrificed at 2, 4, 6, 8, and 10 weeks after the operation, with histological sections obtained in each time point (n = 4 / time point / group). Semi-quantitative histological evaluation was performed in accordance with the Bonar score. The variables included in this scoring system were cell morphology, ground substance, collagen arrangement, and vascularity, with higher grades indicating worse tendon structures. In addition, the ratio of the collagen fibers to the entire tendon tissue (FT ratio) was measured using KS400 software as a quantitative histological evaluation.ResultsThe total Bonar score in the PRP group was significantly lower than in control group. With regard to the variables in the Bonar score, the vascularity score was significantly higher in the PRP group at 2 and 4 weeks, while the collagen arrangement score was significantly lower in the PRP group at 8 weeks. Based on a quantitative evaluation, the recovery speed of the patellar tendon determined by FT ratio was significantly faster in the PRP group than in the control group at 6 and 8 weeks.ConclusionsWe have developed an experimental method for histological and quantitative evaluation of the effects of PRP on tissue healing using murine patellar tendon injury model. The results of this study suggest that the local application of PRP could enhance the tissue-healing process both directly through action on localized cells and indirectly through the recruitment of reparative cells through the blood flow. Further investigations will be needed to confirm the mechanisms of PRP in tissue-healing processes with the development of this experimental model.

Realization and characterization of double-layer Ca-P coating on WE43 Mg alloy for biomedical applications

Biodegradable magnesium (Mg) and some of its alloys are expected to degrade in the human body in consort with the bone tissue healing process. However, the rapid corrosion rate of Mg and its alloys in the physiological environment hinder their applications as implant materials. In this study, we fabricated a double-layer Ca-P coating on the surface of WE43 Mg alloy with enhanced corrosion resistance. The WE43 alloy was firstly anodized and then coated with dicalcium phosphate dihydrate (CaHPO4·2H2O, DCPD) and hydroxyapatite (Ca10(PO4)6(OH)2, HA) layers, consecutively. The coating morphologies and mechanical properties of the DCPD- and HA-coated samples were characterized using SEM, XRD, FTIR, microhardness and pull-out tests. The corrosion behavior of the coated and uncoated samples was assessed by immersion in modified simulated body fluid (m-SBF) and potentiodynamic polarization tests. Results indicated that the DCPD coating was transformed into a compact and crack-free HA coating through an alkali treatment. The microhardness and adhesion strength of the HA-coating were significantly enhanced compared to the other samples. The HA-coated WE43 exhibited the lowest hydrogen gas evolution, degradation rate and the highest corrosion resistance in m-SBF among all samples.

The effect of smoking on back pain intensity in rehabilitated patients treated conservatively and surgically for discopathy

Back pain is now a very common phenomenon. It is caused by various pathologies in the area of the motor unit of the spine. These changes can cause pressure on the nerve structures within the spinal canal, resulting in various ailments. Pain is the most common symptom. In most cases, patients are qualified for conservative management. In the case of neurological deficits, the patient is qualified for spinal surgery. Unfortunately, surgical treatment is not always 100% effective therapy method. Moreover, many external factors, such as smoking for instance, can affect the process of tissue healing and decide on the time of recovery. The aim of the study was to assess the impact of smoking on back pain intensity in rehabilitated patients with discopathy treated conservatively and surgically. The study included 41 patients after surgical treatment (9 smokers) and 96 patients (20 smokers) undergoing conservative therapy for back pain due to discopathy. All patients underwent a multidirectional rehabilitation programme at the Department of Rehabilitation and Physical Medicine of the Medical University in Łódź. The Laitinen scale was used to assess the patients' pain. Rehabilitation of patients with back pain due to discopathy had a significant analgesic effect (p <0.0001). Furthermore, there was observed a statistically significant effect of smoking on the level of pain intensity on the Laitinen scale in the group of patients who underwent surgery (p <0.0469). The smokers operated on had significantly worse results. 1) Complex rehabilitation of patients with back syndrome pain due to discopathy demonstrated significant analgesic effectiveness. 2) Smoking significantly worsens the results of the therapy in patients who underwent surgery.

Mechano-active biomaterials for tissue repair and regeneration

There is a lack of effective tissue repair and regeneration strategies in current clinical practices. Numerous studies have suggested that smart or responsive biomaterials possessing the ability to respond to endogenous stimuli in vivo may positively mediate the tissue micro-environment towards a tissue repair or regeneration. Mechanical stimuli, which constantly exist in a wide range of biological systems and are involved in almost all the physiological processes, belong to such stimuli to which responsive biomaterials can respond. In recent studies, a new type of smart biomaterials, which can dynamically adapt to the mechanical stimuli in vivo and thus has specific functionality consistently mediated by such mechanical stimuli, has emerged. In contrast to common biomaterials that passively react to the mechanical environment of an implantation site, such mechano-active biomaterials have enabled various active or automatic strategies for tissue repair or regeneration, such as providing precise spatial-temporal controls on delivery of drugs or cells in the organs of the musculoskeletal and the circulatory systems; in situ reconstructing the original or a favorable mechanical environment at a lesion site; and accelerating the tissue remodeling or healing process via a mechanobiological effect. This article elucidates a perspective of perfecting tissue repair or regeneration using mechano-active biomaterials, especially highlighting the rationale behind the concept of mechano-active biomaterials and their potential in the repair or regeneration of musculoskeletal and cardiovascular tissues. Albeit outstanding challenges and unknowns, the emergence of mechano-active biomaterials has become a new avenue for tissue engineering and regenerative medicine.

In situ electrical stimulation for enhanced bone growth: A mini‐review

AbstractThe role of electrical stimuli in directing cellular activities during natural tissue healing and regeneration process has been well recognized. This observation has prompted the development and use of exogenous electrical stimulations in the treatment of delayed unions and non‐unions of bone fracture in different parts of the human skeletal system. Considerable amount of clinical evidences has also been generated on the benefits of exogenous bone growth stimulators. However, the clinical efficacy and safety of these exogenous electrical stimulating methods are being argued to be inconsistent and inconclusive, due to lack of sufficient number of well‐controlled, randomized clinical studies. As a result, there has been significant interest in the development of smart biomaterials, which can generate in situ electrical stimuli, for accelerated bone repair, healing and regeneration. These smart biomaterials are essentially either composite biomaterials containing electrically active materials or biomaterials that can be polarized. The primary objective of this mini review was to provide an overview of different exogenous electrical stimulation methods and biocomposites for in situ stimulation, which can be used for bone growth and healing. The first part is focused on exogenous stimulation methods, and the second part discusses the use of biocomposites containing electrically active materials such as piezoelectric materials and multiferroic materials for accelerated repair and regeneration of bone.

Comparison of the effects of systemic and subcutaneous injection of recombinant human erythropoietin on the tissue-healing process in BALB/c Mice

Introduction: Erythropoietin (EPO) is a glycoprotein hormone that is secreted for biological responses and is regulated by the interaction between EPO and specific cytokine receptors. The EPO is a mediator of angiogenesis and erythropoiesis and can increase several growth factors. The current research aimed to compare the effects of systemic and subcutaneous injection of recombinant human EPO on the tissue-healing process. Methods: For the purposes of the study, 30 male BALB/c mice were selected and divided into three groups. The first one received EPO treatment with systemic injection (n=10) while the second one received EPO treatment with subcutaneous injection (n=10). The third group was the control or placebo group without any treatment (n=10). The biopsies were studied on days 4, 7, 10, and 14 through staining by hematoxylin-eosin and Mallory's trichrome. In each group, 3 mice were sacrificed due to exposure to high doses of anesthetic on days 4 and 7. Moreover, 2 other mice were sacrificed after 10 and 14 days. The collected data and images were analyzed in SPSS (version 18.0) and ImageJ software, respectively. Furthermore, they were analyzed using Wilcoxon signed-rank and analysis of variance tests in. During all the analytical processes, a p-value of &lt;0.05 was considered statistically significant Results: According to the results, the density of inflammatory cells significantly decreased in EPO-treated groups, compared to the control group. Moreover, the EPO-treated groups underwent an increase regarding the number of fibroblast cells, new capillary formation, and epithelial thickness in the margins of the wound, unlike the control group. Conclusions: Findings of the present study indicated that the systemic injection of EPO resulted in a better physiological response regarding the acceleration of tissue-healing in comparison with the subcutaneous injection. Furthermore, the systemic injection of EPO improved the parameters related to skin wound repair.

Coating biopolymer nanofibers with carbon nanotubes accelerates tissue healing and bone regeneration through orchestrated cell- and tissue-regulatory responses

Tailoring the surface of biomaterial scaffolds has been a key strategy to modulate the cellular interactions that are helpful for tissue healing process. In particular, nanotopological surfaces have been demonstrated to regulate diverse behaviors of stem cells, such as initial adhesion, spreading and lineage specification. Here, we tailor the surface of biopolymer nanofibers with carbon nanotubes (CNTs) to create a unique bi-modal nanoscale topography (500nm nanofiber with 25nm nanotubes) and report the performance in modulating diverse in vivo responses including inflammation, angiogenesis, and bone regeneration. When administered to a rat subcutaneous site, the CNT-coated nanofiber exhibited significantly reduced inflammatory signs (down-regulated pro-inflammatory cytokines and macrophages gathering). Moreover, the CNT-coated nanofibers showed substantially promoted angiogenic responses, with enhanced neoblood vessel formation and angiogenic marker expression. Such stimulated tissue healing events by the CNT interfacing were evidenced in a calvarium bone defect model. The in vivo bone regeneration of the CNT- coated nanofibers was significantly accelerated, with higher bone mineral density and up-regulated osteogenic signs (OPN, OCN, BMP2) of in vivo bone forming cells. The in vitro studies using MSCs could demonstrate accelerated adhesion and osteogenic differentiation and mineralization, supporting the osteo-promoting mechanism behind the in vivo bone forming event. These findings highlight that the CNTs interfacing of biopolymer nanofibers is highly effective in reducing inflammation, promoting angiogenesis, and driving adhesion and osteogenesis of MSCs, which eventually orchestrate to accelerate tissue healing and bone regeneration process. STATEMENT OF SIGNIFICANCE: Here we demonstrate that the interfacing of biopolymer nanofibers with carbon nanotubes (CNTs) could modulate multiple interactions of cells and tissues that are ultimately helpful for the tissue healing and bone regeneration process. The CNT-coated scaffolds significantly reduced the pro-inflammatory signals while stimulating the angiogenic marker expressions. Furthermore, the CNT-coated scaffolds increased the bone matrix production of bone forming cells in vivo as well as accelerated the adhesion and osteogenic differentiation of MSCs in vitro. These collective findings highlight that the CNTs coated on the biopolymer nanofibers allow the creation of a promising platform for nanoscale engineering of biomaterial surface that can favor tissue healing and bone regeneration process, through a series of orchestrated events in anti-inflammation, pro-angiogenesis, and stem cell stimulation.

The Role of Marine Organic Extract in Bone Regeneration: A Pilot Study.

Novel biomaterials capable of accelerating the healing process of skeletal tissues are urgently needed in dentistry. The present in vivo study assessed the osteoconductive and osteoinductive properties of experimental biphasic bioceramics (HA-TCP) modified or not by a nacre extract (marine organic extract, MOE) in a sheep model. Fabrication of MOE involved mixing ground nacre (0.05 g, particle sizes < 0.1 mm) with glacial ethanoic acid (5 mL, pH 7) for 72 hours using external magnetic stirring (25°C). Nonreactive carriers (sterile polythene tubes; 3/animal, radius: 2.5 mm, length: 10.0 mm) pertaining to the control (empty) or experimental groups (HA-TCP or MOE-modified HA-TCP) were implanted intramuscularly into the abdominal segment of the torso in sheep (n = 8, age: 2 years, weight: 45 kg). Euthanization of animals was performed at 3 and 6 months after surgery. Tissues harvested were subjected to macroscopic and radiographic assessments. Specimens were then stained for histological analysis. Both control and experimental animals were capable of inducing the neoformation of fibrous connective tissue at both time points where superior amounts of tissue formation and mineralization were detected for experimental groups (unaltered (at 3 and 6 mos) and MOE-modified HA-TCP (at 3 mos)). Histological results, however, revealed that mature bone formation was only observed for specimens fabricated with MOE-modified HA-TCP in a time-dependent manner. The present study has successfully demonstrated the in vivo utility of experimental biphasic bioceramics modified by MOE in an ectopic grafting sheep model. Promising osteoconductive and osteoinductive properties must be further developed and confirmed by subsequent research.

Pulp-Dentin Tissue Healing Response: A Discussion of Current Biomedical Approaches.

Dental pulp tissue exposed to mechanical trauma or cariogenic process results in root canal and/or periapical infections, and conventionally treated with root canal procedures. The more recent regenerative endodontic procedure intends to achieve effective root canal disinfection and adequate pulp–dentin tissue regeneration; however, numerous limitations are reported. Because tooth is composed of vital soft pulp enclosed by the mineralized hard tissue in a highly organized structure, complete pulp–dentin tissue regeneration has been challenging to achieve. In consideration of the limitations and unique dental anatomy, it is important to understand the healing and repair processes through inflammatory-proliferative-remodeling phase transformations of pulp–dentin tissue. Upon cause by infectious and mechanical stimuli, the innate defense mechanism is initiated by resident pulp cells including immune cells through chemical signaling. After the expansion of infection and damage to resident pulp–dentin cells, consequent chemical signaling induces pluripotent mesenchymal stem cells (MSCs) to migrate to the injury site to perform the tissue regeneration process. Additionally, innovative biomaterials are necessary to facilitate the immune response and pulp–dentin tissue regeneration roles of MSCs. This review highlights current approaches of pulp–dentin tissue healing process and suggests potential biomedical perspective of the pulp–dentin tissue regeneration.

Does the Application of Tecar Therapy Affect Temperature and Perfusion of Skin and Muscle Microcirculation? A Pilot Feasibility Study on Healthy Subjects.

Background: Tecar therapy (TT) is an endogenous thermotherapy used to generate warming up of superficial and deep tissues. TT capability to affect the blood flow is commonly considered to be the primary mechanism to promote tissue healing processes. Despite some preliminary evidence about its clinical efficacy, knowledge on the physiologic responses induced by TT is lacking.Objective: The aim of this quantitative randomized pilot study was to determinate if TT, delivered in two modes (resistive and capacitive), affects the perfusion of the skin microcirculation (PSMC) and intramuscular blood flow (IMBF).Design: A randomized controlled pilot feasibility study.Subjects: Ten healthy volunteers (n = 4 females, n = 6 males; mean age 35.9 ± 10.7 years) from a university population were recruited and completed the study.Intervention: All subjects received three different TT applications (resistive, capacitive, and placebo) for a period of 8 min.Outcome measures: PSMC, IMBF, and the skin temperature (ST) were measured pre- and post-TT application using power Doppler sonography, laser speckle contrast imaging (LSCI), and infrared thermography.Results: Compared with placebo application, statistically significant differences in PSMC resulted after both the resistive (p = 0.0001) and the capacitive (p = 0.0001) TT applications, while only the resistive modality compared with the placebo was capable to induce a significant change of IMBF (p = 0.013) and ST (p = 0.0001).Conclusions: The use of power Doppler sonography and LSCI enabled us to evaluate differences in PSMC and IMBF induced by TT application.

The role of microbiota in tissue repair and regeneration.

A comprehensive understanding of the human body endogenous microbiota is essential for acquiring an insight into the involvement of microbiota in tissue healing and regeneration process in order to enable development of biomaterials with a better integration with human body environment. Biomaterials used for biomedical applications are normally germ-free, and the human body as the host of the biomaterials is not germ-free. The complexity and role of the body microbiota in tissue healing/regeneration have been underestimated historically. Traditionally, studies aiming at the development of novel biomaterials had focused on the effects of environment within the target tissue, neglecting the signals generated from the microbiota and their impact on tissue regeneration. The significance of the human body microbiota in relation to metabolism, immune system, and consequently tissue regeneration has been recently realised and is a growing research field. This review summarises recent findings on the role of microbiota and mechanisms involved in tissue healing and regeneration, in particular skin, liver, bone, and nervous system regrowth and regeneration highlighting the potential new roles of microbiota for development of a new generation of biomaterials.

MiR-184 Inhibits Hypertrophic Scar Through Regulating Phosphatidylinositol 3-Kinase (PI3K)/Protein Kinase B (AKT) Signaling Pathway

Hypertrophic scar (HS) is a process of tissue repair and healing, and excessive fibrosis of local tissue leads to scar formation. During HS formation, fibroblasts (Fb) proliferate, synthesize and secrete and promote HS development. miR-184 regulates skin formation and tissue development. However, miR-184’s role in HS remains unclear. miR-184 expression in HS patients and normal healthy (Control) tissues was measured by real-time PCR. pAKT expression was analyzed by Western blot. Fb cells from human HS were cultured and divided into 2 groups, siRNA NC group and miR-184 siRNA group followed by analysis of miR-184 expression by real time PCR, cell proliferation by MTT assay, secretion of inflammatory factors IL-1β and IL-6 by ELISA, as well as expression of pAKT and AKT by western blot. Compared with control group, miR-184 and pAKT expression was significantly increased in the HS group. Transfection of miR-184 siRNA into Fb significantly downregulated miR-184 expression, inhibited cell proliferation, promoted Caspase 3 activity, decreased IL-1β and IL-6 secretion, and reduced pAKT level (P &lt; 0.05). miR-184 expression is increased in hypertrophic scar tissue. Down-regulation of miR-184 expression in proliferative scar tissue fibroblasts can down-regulate PI3K/AKT signaling pathway, inhibit inflammation, promote apoptosis, inhibit fibroblast proliferation, and regulate hypertrophic scar formation.

Use of radioguided surgery technique for the treatment of thyroid cancer recurrence: clinical, surgical and anatomopathological aspects

Introduction: Surgery is the treatment of choice in locoregional thyroid neoplasia recurrence. The intense tissue healing process observed after surgery changes the neck anatomy, makes reoperation difficult, and interferes with surgical success. The use of the Radioguided Occult Lesion Localization (ROLL) technique has become a viable option to localize thyroid tumors. Objective: To analyze the use of the ROLL technique for the treatment of thyroid cancer recurrence with respect to its clinical, surgical and anatomopathological aspects. Methods: A descriptive cross-sectional study that analyzed 56 medical records and anatomopathological examinations of patients of both sexes who had thyroid neoplasms, underwent previous surgeries on this topography, and were submitted to the ROLL technique for recurrence removal from March 2011 to March 2019. Results: Most patients were women aged 46.05 years, on average. Papillary thyroid neoplasm was the most prevalent histological finding. In 100% of the cases, application of the ROLL technique identified and removed the lesions marked with suspicion for malignancy. Conclusion: Radioguided surgery has proved to be a very effective and safe tool to assist with lesion localization for the treatment of thyroid cancer recurrence. This technique has brought no additional side effects to patients, required minimal radiation and made surgery less invasive, reducing postoperative complication rates.

Effect of platelet rich-fibrin on alveolar osteitis incidence following surgical removal of impacted mandibular third molars: A comparative study

Background: Postoperative morbidity after extraction of the impacted mandibular third molar (IMTM) is inevitable. One of the most common postoperative complication is alveolar osteitis (AO) which is a painful non healed socket. Many researches were attempted to prevent the occurrence of AO by introducing and applying a new materials inside the extraction socket. Platelet rich fibrin (PRF) is a biological complex fibrin matrix where autologous platelets and leucocytes are present, used to enhance tissue healing process and reduce the early adverse effects of the inflammation. Aims: To evaluate the effect of PRF on the incidence of AO. Also to assess PRF effect on pain, swelling, and trismus following the surgical removal of IMTM and compare it with the control group. Materials and methods: This clinical prospective study was conducted from October 2016 to October 2017 at the Department of Oral &amp; Maxillofacial Surgery, College of dentistry/University of Baghdad; and Al-Sadr Specialized Health Center. A total number of 50 IMTMs were surgically removed from 45 patients who met the inclusion criteria (21 males and 24 females) with age ranged from 16-41 years. The cases were divided into two groups: a study group (25 cases) where PRF were placed inside the extraction socket and control group (25 cases) where traditional surgery were performed. AO, trismus and swelling were assessed at the 2nd and 7th postoperative day. Pain scored by numeric rating scale daily by the patients. Results: The study showed that age, gender, side of impaction, oral hygiene condition, impacted tooth classification, surgical difficulty, and the time of procedure in both control and study groups had nearly similar distribution with non- significant difference. At the 1st follow up period: Trismus (P-value = 0.834) and Swelling (P-value = 0.592) were non- significant between the two groups. AO had overall incidence of 4% occurred only in the control group, while the PRF group had no occurrence (0%), but the difference was statistically non significant. Postoperative pain had no significance difference in both groups. At the 2nd follow up period there was no significant difference regarding trismus, swelling, and incidence of AO between both groups. Conclusion: Local application of PRF can reduce the incidence of AO but not to a significant level. PRF had no effect concerning postoperative pain, swelling, and trismus.

Bi-Layered Polymer Carriers with Surface Modification by Electrospinning for Potential Wound Care Applications.

Polymeric wound dressings with advanced properties are highly preferred formulations to promote the tissue healing process in wound care. In this study, a combinational technique was investigated for the fabrication of bi-layered carriers from a blend of polyvinyl alcohol (PVA) and sodium alginate (SA). The bi-layered carriers were prepared by solvent casting in combination with two surface modification approaches: electrospinning or three-dimensional (3D) printing. The bi-layered carriers were characterized and evaluated in terms of physical, physicochemical, adhesive properties and for the safety and biological cell behavior. In addition, an initial inkjet printing trial for the incorporation of bioactive substances for drug delivery purposes was performed. The solvent cast (SC) film served as a robust base layer. The bi-layered carriers with electrospun nanofibers (NFs) as the surface layer showed improved physical durability and decreased adhesiveness compared to the SC film and bi-layered carriers with patterned 3D printed layer. Thus, these bi-layered carriers presented favorable properties for dermal use with minimal tissue damage. In addition, electrospun NFs on SC films (bi-layered SC/NF carrier) provided the best physical structure for the cell adhesion and proliferation as the highest cell viability was measured compared to the SC film and the carrier with patterned 3D printed layer (bi-layered SC/3D carrier). The surface properties of the bi-layered carriers with electrospun NFs showed great potential to be utilized in advanced technical approach with inkjet printing for the fabrication of bioactive wound dressings.

Quantifying Vascular Changes Surrounding Bone Regeneration in a Porcine Mandibular Defect Using Computed Tomography.

Angiogenesis is a critical process essential for optimal bone healing. Several in vitro and in vivo systems have been previously used to elucidate some of the mechanisms involved in the process of angiogenesis, and at the same time, to test potential therapeutic agents and bioactive factors that play important roles in neovascularization. Computed tomography (CT) is a noninvasive imaging technique that has recently allowed investigators to obtain a diverse range of high-resolution, three-dimensional characterization of structures, such as bone formation within bony defects. Unfortunately, to date, angiogenesis evaluation relies primarily on histology, or ex vivo imaging and few studies have utilized CT to qualitatively and quantitatively study the vascular response during bone repair. In the current study a clinical CT-based technique was used to evaluate the effects of rhBMP-2 eluting graft treatment on soft tissue vascular architecture surrounding a large segmental bone defect model in the minipig mandible. The objective of this study was to demonstrate the efficacy of contrast-enhanced, clinical 64-slice CT technology in extracting quantitative metrics of vascular architecture over a 12-week period. The results of this study show that the presence of rhBMP-2 had a positive effect on vessel volume from 4 to 12 weeks, which was explained by a concurrent increase in vessel number, which was also significantly higher at 4 weeks for the rhBMP-2 treatment. More importantly, analysis of vessel architecture showed no changes throughout the duration of the study, indicating therapeutic safety. This study validates CT analysis as a relevant imaging method for quantitative and qualitative analysis of morphological characteristics of vascular tissue around a bone healing site. Also important, the study shows that CT technology can be used in large animal models and potentially be translated into clinical models for the development of improved methods to evaluate tissue healing and vascular adaptation processes over the course of therapy. This methodology has demonstrated sensitivity to tracking spatial and temporal changes in vascularization and has the potential to be applied to studying changes in other high-contrast tissues as well. Impact Statement Tissue engineering solutions depend on the surrounding tissue response to support regeneration. The inflammatory environment and surrounding vascular supply are critical to determining if therapies will survive, engraftment occurs, and native physiology is restored. This study for the first time evaluates the blood vessel network changes in surrounding soft tissue to a bone defect site in a large animal model, using clinically available computed tomography tools and model changes in vessel number, size, and architecture. While this study focuses on rhBMP2 delivery impacting surrounding vasculature, this validated method can be extended to studying the vascular network changes in other tissues as well.

Near-Infrared-Triggered Dynamic Surface Topography for Sequential Modulation of Macrophage Phenotypes.

Immune response is critical to tissue repair. Designing biomaterials with immunomodulatory functions has become a promising strategy to facilitate tissue repair. Considering the key roles of macrophages in tissue repair and the significance of the balance of M1 and M2, smart biomaterials, which can harness macrophage phenotypes dynamically to match the tissue healing process on demand, have attracted a lot of attention to be set apart from the traditional anti-inflammatory biomaterials. Here, we prepare a gold nanorod-contained shape memory polycaprolactone film with dynamic surface topography, which has the ability to be transformed from flat to microgrooved under near-infrared (NIR) irradiation. Based on the close relationships between the morphologies and the phenotypes of macrophages, the NIR-triggered surface transformation induces the elongation of macrophages, and consequently the upregulated expressions of arginase-1 and IL-10 in vitro, indicating the change of macrophage phenotypes. The sequential modulation of macrophage phenotypes by dynamic surface topography is further confirmed in an in vivo implantation test. The healing-matched modulation of macrophage phenotypes by dynamic surface topography without the stimuli of cytokines offers an effective and noninvasive strategy to manipulate tissue regenerative immune reactions to achieve optimized healing outcomes.

Сучасні фізичні методи стимуляції процесів загоєння кісткової тканини

Сучасні фізичні методи стимуляції процесів загоєння кісткової тканини

Interacting adipose-derived stem cells and microvascular endothelial cells provide a beneficial milieu for soft tissue healing.

There is growing evidence suggesting that healing of chronic soft tissue wounds profits from the presence of adipose-derived stem cells (ADSC). Among the large spectrum of mechanisms by which ADSC might act, especially the interaction with the microvascular endothelial cell, a main player during angiogenesis, is of special interest. In the present 2D model on the basis of endothelial cell ADSC co-cultures, we focused on the identification of characteristics of both cell types in response to a typical condition in acute and chronic wounds: hypoxia. Parameters like proliferation capacity, migration, myofibroblastoid differentiation of ADSC and the quantification of important paracrine factors related to angiogenesis and inflammation were used to correlate our experimental model with the in vivo situation of soft tissue healing. ADSC were not negatively affected by hypoxia in terms of proliferation, referring to their excellent hypoxia tolerance. Myofibroblastoid differentiation among ADSC was enhanced by hypoxia in mono- but not in co-culture. Furthermore, co-cultures were able to migrate under hypoxia. These effects might be caused to some extent by the distinct milieu created by interacting ADSC and endothelial cells, which was characterized by modulated levels of interleukin-6, interleukin-8, monocyte chemoattractant protein-1 and vascular endothelial growth factor. The identification of these cell characteristics in the present 2D in vitro model provide new insights into the process of human soft tissue healing, and underpin a beneficial role of ADSC by regulating inflammation and angiogenesis.

Pioglitazone-loaded three-dimensional composite polymeric scaffolds: A proof of concept study in wounded diabetic rats.

Diabetic patients suffer from impaired wound healing. In this study, the anti-diabetic drug, Pioglitazone hydrochloride (PG), was loaded in three-dimensional (3D) composite scaffolds (SC) designed to be applied topically for the management of diabetic wounds. Hydroxypropyl methyl cellulose (HPMC) of different molecular weight (E5, K4M or K15M) were used, in different ratios, with chitosan (CS) for the preparation of the 3D-SC. Investigations to examine the prepared SCs revealed that SC-F3 composed of CS /HPMC E5 (2:1) attained the highest porosity (99.12 ± 5.01), highest water absorption capacity % (300.09 ± 20.20), and attained the fastest drug release profile (p < 0.05), with release kinetics following the diffusion model. SEM microphotographs showed the highly porous structure of SC-F3. According to the modified Draize test, the selected 3D-SC (the medicated as well as the unmedicated) showed to be safe for skin application (PII = 0). During the in-vivo studies, both the selected PG-loaded SC and the unmedicated SC showed a significant improvement in the healing process compared to the untreated group, this was evidenced by the measurement of wound contraction % [627% and 467%, respectively, p < 0.05], as well as the level of some biomarkers (TNF-α, VEGF and MMP-9). PG-loaded SC had a significantly better effect than the unmedicated SC (p < 0.05). Histopathological studies confirmed the complete tissue regeneration and healing process after the use of the selected PG-loaded scaffolds. The current study presents a feasible approach to support diabetic wound healing using a simple and safe formulation.