The Combination of Bioactive Herbal Compounds with Biomaterials for Regenerative Medicine.

Regenerative medicine aims to restore the function of diseased or damaged tissues and organs by cell therapy, gene therapy, and tissue engineering, along with the adjunctive application of bioactive molecules. Traditional bioactive molecules, such as growth factors and cytokines, have shown great potential in the regulation of cellular and tissue behavior, but have the disadvantages of limited source, high cost, short half-life, and side effects. In recent years, herbal compounds extracted from natural plants/herbs have gained increasing attention. This is not only because herbal compounds are easily obtained, inexpensive, mostly safe, and reliable, but also owing to their excellent effects, including anti-inflammatory, antibacterial, antioxidative, proangiogenic behavior and ability to promote stem cell differentiation. Such effects also play important roles in the processes related to tissue regeneration. Furthermore, the moieties of the herbal compounds can form physical or chemical bonds with the scaffolds, which contributes to improved mechanical strength and stability of the scaffolds. Thus, the incorporation of herbal compounds as bioactive molecules in biomaterials is a promising direction for future regenerative medicine applications. Herein, an overview on the use of bioactive herbal compounds combined with different biomaterial scaffolds for regenerative medicine application is presented. We first introduce the classification, structures, and properties of different herbal bioactive components and then provide a comprehensive survey on the use of bioactive herbal compounds to engineer scaffolds for tissue repair/regeneration of skin, cartilage, bone, neural, and heart tissues. Finally, we highlight the challenges and prospects for the future development of herbal scaffolds toward clinical translation. Overall, it is believed that the combination of bioactive herbal compounds with biomaterials could be a promising perspective for the next generation of regenerative medicine.

Developing Chinese herbal-based functional biomaterials for tissue engineering.

The role of traditional Chinese medicine (TCM) in treating diseases is receiving increasing attention. Chinese herbal medicine is an important part of TCM with various applications and the active ingredients extracted from Chinese herbal medicines have physiological and pathological effects. Tissue engineering combines cell biology and materials science to construct tissues or organs in vitro or in vivo. TCM has been proposed by the World Health Organization as an effective treatment modality. In recent years, the potential use of TCM in tissue engineering has been demonstrated. In this review, the classification and efficacy of TCM active ingredients and delivery systems are discussed based on the TCM theory. We also summarized the current application status and broad prospects of Chinese herbal active ingredients in different specialized biomaterials in the field of tissue engineering. This review provides novel insights into the integration of TCM and modern Western medicine through the application of Chinese medicine in tissue engineering and regenerative medicine.

Organic-inorganic biohybrid films from wool-keratin/jellyfish-collagen/silica/boron via sol-gel reactions for soft tissue engineering applications.

Therapeutic angiogenesis is pivotal in creating effective tissue-engineered constructs that deliver nutrients and oxygen to surrounding cells. Hence, biomaterials that promote angiogenesis can enhance the efficacy of various medical treatments, encompassing tissue engineering, wound healing, and drug delivery systems. Considering these, we propose a rapid method for producing composite silicon-boron-wool keratin/jellyfish collagen (Si-B-WK/JFC) inorganic-organic biohybrid films using sol-gel reactions. In this approach, reactive tetraethyl orthosilicate and boric acid (pKa ⩾ 9.24) were used as silicon and boron sources, respectively, and a solid-state gel was formed through the condensation reaction of these reactive groups with the keratin/collagen mixture. Once the resulting gel was thoroughly suspended in water, the films were prepared by a casting/solvent evaporation methodology. The fabricated hybrid films were characterized structurally and mechanically. In addition, angiogenic characteristics were determined by the in ovo chick chorioallantoic membrane assay, which revealed an increased vascular network within the Si-B-WK/JFC biohybrid films. In conclusion, it is believed that Si-B-WK/JFC biohybrid films with mechanical and pro-angiogenic properties have the potential to be possessed in soft tissue engineering applications, especially wound healing.

Mesenchymal Stem Cell-based Scaffolds in Regenerative Medicine of Dental Diseases.

Biomedical engineering breakthroughs and increased patient expectations and requests for more comprehensive care are propelling the field of regenerative dentistry forward at a fast pace. Stem cells (SCs), bioactive compounds, and scaffolds are the mainstays of tissue engineering, the backbone of regenerative dentistry. Repairing damaged teeth and gums is a significant scientific problem at present. Novel therapeutic approaches for tooth and periodontal healing have been inspired by tissue engineering based on mesenchymal stem cells (MSCs). Furthermore, as a component of the MSC secretome, extracellular vesicles (EVs) have been shown to contribute to periodontal tissue repair and regeneration. The scaffold, made of an artificial extracellular matrix (ECM), acts as a supporting structure for new cell development and tissue formation. To effectively promote cell development, a scaffold must be non-toxic, biodegradable, biologically compatible, low in immunogenicity, and safe. Due to its promising biological characteristics for cell regeneration, dental tissue engineering has recently received much attention for its use of natural or synthetic polymer scaffolds with excellent mechanical properties, such as small pore size and a high surface-to-volume ratio, as a matrix. Moreover, as a bioactive material for carrying MSC-EVs, the combined application of scaffolds and MSC-EVs has a better regenerative effect on dental diseases. In this paper, we discuss how MSCs and MSC-derived EV treatment may be used to regenerate damaged teeth, and we highlight the role of various scaffolds in this process.

Designing bioinspired multifunctional nanoplatforms to support wound healing and skin regeneration: Mg-hydroxyapatite meets melanins.

Melanin is a multifunctional biological pigment that recently emerged as endowed with anti-inflammatory, antioxidant, and antimicrobial properties and with high potentialities in skin protection and regenerative medicine. Here, a biomimetic magnesium-doped nano-hydroxyapatite (MgHA) was synthesized and decorated with melanin molecules starting from two different monomeric precursors, i.e. 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and dopamine (DA), demonstrating to be able to polymerize on the surface of MgHA nanostructures, thus leading to a melanin coating. This functionalization was realized by a simple and green preparation method requiring mild conditions in an aqueous medium and room temperature. Complementary spectroscopy and electron imaging analyses were carried out to define the effective formation of a stable coating, the percentage of the organic compounds, and the structural properties of resulting melanin-coated nanostructures, which showed good antioxidant activity. The in vitro interaction with a cell model, i.e. mouse fibroblasts, was investigated. The excellent biocompatibility of all bioinspired nanostructures was confirmed from a suitable cell proliferation. Finally, the enhanced biological performances of the nanostructures coated with melanin from DHICA were confirmed by scratch assays. Jointly our findings indicated that low crystalline MgHA and melanin pigments can be efficiently combined, and the resulting nanostructures are promising candidates as multifunctional platforms for a more efficient approach for skin regeneration and protection.

The story of melanocyte: a long way from bench to bedside.

Skin is composed of major layers, namely a superficial epidermis and a deeper dermis. The color of skin is influenced by a number of pigments, including melanin, which is produced by cells called melanocytes. Most skin disorders are relatively benign, but a few, including melanomas, can be fatal. A number of more noticeable disorders, namely albinism and vitiligo, affect the appearance of the skin and its accessory organs. Vitiligo is associated with significant psycho-social morbidity and a major effect on quality of life. Topical steroids, calcineurin inhibitors, phototherapy and surgery are the most common treatments for melanoma. However, there are many patients who do not respond to any of these modalities. The transplantation of cultured or non-cultured melanocyte is the most important treatment for hypopigmentory disorders. This study aims at reviewing the history of melanocyte cultivation, and evaluating the effectiveness of transplantation of cultured cells. For this purpose, the authors examined the initial process of isolation, characterization, and transplantation of epidermal cells. This review, thus, summarizes the current understanding of the cutaneous pigmentary system from the start of synthesis in the pigment cells, along with the response of repigmentation. During the production of melanin, melanosomes are transferred to neighboring keratinocyte in order to form perinuclear melanin caps. The objective of this review is to analyze the melanocytes transplantation in the last century to date, and explore the methods epidermal cells can increase pigmentation in hypo-pigmented areas in skin disorders. Moreover, the focus is on the story of the melanocyte back to 1950s. In addition, prior systemic therapy was associated with a significant increase, based on combined additional therapy, achieving desired results and improved outcomes. Despite the short study of a long way of melanocyte assessment and following up patient treatment, results of the all reports confirmed the efficacy of the method used in the treatment of stable vitiligo patients, who did not respond to the common algorithms of non-invasive treatments.

Metal Organic Framework-Incorporated Three-Dimensional (3D) Bio-Printable Hydrogels to Facilitate Bone Repair: Preparation and In Vitro Bioactivity Analysis.

Hydrogels are three-dimensional (3D) water-swellable polymeric matrices that are used extensively in tissue engineering and drug delivery. Hydrogels can be conformed into any desirable shape using 3D bio-printing, making them suitable for personalized treatment. Among the different 3D bio-printing techniques, digital light processing (DLP)-based printing offers the advantage of quickly fabricating high resolution structures, reducing the chances of cell damage during the printing process. Here, we have used DLP to 3D bio-print biocompatible gelatin methacrylate (GelMA) scaffolds intended for bone repair. GelMA is biocompatible, biodegradable, has integrin binding motifs that promote cell adhesion, and can be crosslinked easily to form hydrogels. However, GelMA on its own is incapable of promoting bone repair and must be supplemented with pharmaceutical molecules or growth factors, which can be toxic or expensive. To overcome this limitation, we introduced zinc-based metal-organic framework (MOF) nanoparticles into GelMA that can promote osteogenic differentiation, providing safer and more affordable alternatives to traditional methods. Incorporation of this nanoparticle into GelMA hydrogel has demonstrated significant improvement across multiple aspects, including bio-printability, and favorable mechanical properties (showing a significant increase in the compressive modulus from 52.14 ± 19.42 kPa to 128.13 ± 19.46 kPa with the addition of ZIF-8 nanoparticles). The designed nanocomposite hydrogels can also sustain drug (vancomycin) release (maximum 87.52 ± 1.6% cumulative amount) and exhibit a remarkable ability to differentiate human adipose-derived mesenchymal stem cells toward the osteogenic lineage. Furthermore, the formulated MOF-integrated nanocomposite hydrogel offers the unique capability to coat metallic implants intended for bone healing. Overall, the remarkable printability and coating ability displayed by the nanocomposite hydrogel presents itself as a promising candidate for drug delivery, cell delivery and bone tissue engineering applications.

Efficient Differentiation of Human Induced Pluripotent Stem Cell (hiPSC)-Derived Mesenchymal Progenitors Into Adipocytes and Osteoblasts.

Human induced pluripotent stem cells (hiPSCs) hold immense promise in regenerative medicine as they can differentiate into various cell lineages, including adipocytes, osteoblasts, and chondrocytes. Precisely guiding hiPSC-derived mesenchymal progenitor cells (iMSCs) towards specific differentiation pathways is crucial for harnessing their therapeutic potential in tissue engineering, disease modeling, and regenerative therapies. To achieve this, we present a comprehensive and reproducible protocol for effectively differentiating iMSCs into adipocytes and osteoblasts. The differentiation process entails culturing iMSCs in tailored media supplemented with specific growth factors, which act as cues to initiate adipogenic or osteogenic commitment. Our protocol provides step-by-step guidelines for achieving adipocyte and osteoblast differentiation, ensuring the generation of mature and functional cells. To validate the success of differentiation, key assessment criteria are employed. For adipogenesis, the presence of characteristic lipid droplets within the iMSC-derived cells is considered indicative of successful differentiation. Meanwhile, Alizarin Red staining serves as a marker for the osteogenic differentiation, confirming the formation of mineralized nodules. Importantly, the described method stands out due to its simplicity, eliminating the need for specialized equipment, expensive materials, or complex reagents. Its ease of implementation offers an attractive advantage for researchers seeking robust and cost-effective approaches to derive adipocytes and osteoblasts from iMSCs. Overall, this protocol establishes a foundation for exploring the therapeutic potential of hiPSC-derived cells and advancing the field of regenerative medicine. Key features • iMSC derivation in this protocol uses embryonic body formation technique. • Adipogenesis and osteogenesis protocols were optimized for human iPSC-derived iMSCs. • Derivation of iMSC from hiPSC was developed in a feeder-free culture condition. • This protocol does not include human iPSC reprogramming strategies.

Potential application of PBM use in hair follicle organoid culture for the treatment of androgenic alopecia.

Androgenic alopecia is a hereditary condition of pattern hair loss in genetically susceptible individuals. The condition has a significant impact on an individual's quality of life, with decreased self-esteem, body image issues and depression being the main effects. Various conventional treatment options, such as minoxidil, finasteride and herbal supplements, aim to slow down hair loss and promote hair growth. However, due to the chronic nature of the condition the financial cost of treatment for androgenic alopecia is very high and conventional treatment options are not universally effective and come with a host of side effects. Therefore, to address the limitations of current treatment options a novel regenerative treatment option is required. One promising approach is organoids, organoids are 3D cell aggregates with similar structures and functions to a target organ. Hair follicle organoids can be developed in vitro. However, the main challenges are to maintain the cell populations within the organoid in a proliferative and inductive state, as well as to promote the maturation of organoids. Photobiomodulation is a form of light therapy that stimulates endogenous chromophores. PBM has been shown to improve cell viability, proliferation, migration, differentiation and gene expression in dermal papilla cells and hair follicle stem cells. Therefore, photobiomodulation is a potential adjunct to hair follicle organoid culture to improve the proliferation and inductive capacity of cells.

An in vitro model system based on calcium- and phosphate ion-induced hMSC spheroid mineralization.

A challenge in regenerative medicine is creating the three-dimensional organic and inorganic in vitro microenvironment of bone, which would allow the study of musculoskeletal disorders and the generation of building blocks for bone regeneration. This study presents a microwell-based platform for creating spheroids of human mesenchymal stromal cells, which are then mineralized using ionic calcium and phosphate supplementation. The resulting mineralized spheroids promote an osteogenic gene expression profile through the influence of the spheroids' biophysical environment and inorganic signaling and require less calcium or phosphate to achieve mineralization compared to a monolayer culture. We found that mineralized spheroids represent an in vitro model for studying small molecule perturbations and extracellular mediated calcification. Furthermore, we demonstrate that understanding pathway signaling elicited by the spheroid environment allows mimicking these pathways in traditional monolayer culture, enabling similar rapid mineralization events. In sum, this study demonstrates the rapid generation and employment of a mineralized cell model system for regenerative medicine applications.

Potential use of iPSCs for disease modeling, drug screening, and cell-based therapy for Alzheimer's disease.

Alzheimer's disease (AD) is a chronic illness marked by increasing cognitive decline and nervous system deterioration. At this time, there is no known medication that will stop the course of Alzheimer's disease; instead, most symptoms are treated. Clinical trial failure rates for new drugs remain high, highlighting the urgent need for improved AD modeling for improving understanding of the underlying pathophysiology of disease and improving drug development. The development of induced pluripotent stem cells (iPSCs) has made it possible to model neurological diseases like AD, giving access to an infinite number of patient-derived cells capable of differentiating neuronal fates. This advance will accelerate Alzheimer's disease research and provide an opportunity to create more accurate patient-specific models of Alzheimer's disease to support pathophysiological research, drug development, and the potential application of stem cell-based therapeutics. This review article provides a complete summary of research done to date on the potential use of iPSCs from AD patients for disease modeling, drug discovery, and cell-based therapeutics. Current technological developments in AD research including 3D modeling, genome editing, gene therapy for AD, and research on familial (FAD) and sporadic (SAD) forms of the disease are discussed. Finally, we outline the issues that need to be elucidated and future directions for iPSC modeling in AD.

Harmonizing Magnetic Mitohormetic Regenerative Strategies: Developmental Implications of a Calcium-Mitochondrial Axis Invoked by Magnetic Field Exposure.

Mitohormesis is a process whereby mitochondrial stress responses, mediated by reactive oxygen species (ROS), act cumulatively to either instill survival adaptations (low ROS levels) or to produce cell damage (high ROS levels). The mitohormetic nature of extremely low-frequency electromagnetic field (ELF-EMF) exposure thus makes it susceptible to extraneous influences that also impinge on mitochondrial ROS production and contribute to the collective response. Consequently, magnetic stimulation paradigms are prone to experimental variability depending on diverse circumstances. The failure, or inability, to control for these factors has contributed to the existing discrepancies between published reports and in the interpretations made from the results generated therein. Confounding environmental factors include ambient magnetic fields, temperature, the mechanical environment, and the conventional use of aminoglycoside antibiotics. Biological factors include cell type and seeding density as well as the developmental, inflammatory, or senescence statuses of cells that depend on the prior handling of the experimental sample. Technological aspects include magnetic field directionality, uniformity, amplitude, and duration of exposure. All these factors will exhibit manifestations at the level of ROS production that will culminate as a unified cellular response in conjunction with magnetic exposure. Fortunately, many of these factors are under the control of the experimenter. This review will focus on delineating areas requiring technical and biological harmonization to assist in the designing of therapeutic strategies with more clearly defined and better predicted outcomes and to improve the mechanistic interpretation of the generated data, rather than on precise applications. This review will also explore the underlying mechanistic similarities between magnetic field exposure and other forms of biophysical stimuli, such as mechanical stimuli, that mutually induce elevations in intracellular calcium and ROS as a prerequisite for biological outcome. These forms of biophysical stimuli commonly invoke the activity of transient receptor potential cation channel classes, such as TRPC1.

Current Non-surgical Management of Knee Osteoarthritis.

Osteoarthritis (OA) is a common chronic degenerative disease. The prevalence tends to increase with age and is influenced by underlying risk factors such as gender, obesity, joint injuries (work/sports activities), and geographic region. OA has a distinctive picture, namely, damage to the joint cartilage and the formation of new bone at the edges of the bones, also called osteophytes, due to biochemical, metabolic, physiological, and pathological changes in the joint cartilage and subchondral bone. Symptoms that can be caused include joint pain, inhibition of joint movement, crepitus, deformity, asymmetrical swelling of the joints, signs of inflammation, and changes in gait. Currently, there are various methods of managing OA in terms of reducing pain, including regeneration and non-regeneration therapy. Non-regeneration treatments include physiotherapy (exercise, biomechanical intervention, electrotherapy, diathermy), pharmacology, intra-articular injections (corticosteroids, hyaluronic acid, geniculate nerve blocks), extra-articular injections, and radiofrequency. In comparison, regeneration management includes laser and intra-articular injection (prolotherapy and PRP).

Response to comment on 'A conserved strategy for inducing appendage regeneration in moon jellyfish, Drosophila, and mice'.

Previously we reported evidence that a regenerative response in the appendages of moon jellyfish, fruit flies, and mice can be promoted by nutrient modulation (Abrams et al., 2021). Sustar and Tuthill subsequently reported that they had not been able to reproduce the induced regenerative response in flies (Sustar and Tuthill, 2023). Here we discuss that differences in the amputation method, treatment concentrations, age of the animals, and stress management explain why they did not observe a regenerative response in flies. Typically, 30-50% of treated flies showed response in our assay.

Comment on 'A conserved strategy for inducing appendage regeneration in moon jellyfish, Drosophila, and mice'.

Abrams et al. report that a simple dietary supplement is sufficient to induce appendage regeneration in jellyfish, fruit flies, and mice (Abrams et al., 2021). This conclusion is surprising because it was previously thought that flies and mice lack the capacity for regeneration after injury. We replicated the Drosophila experiments of Abrams et al. but did not observe any instances of leg regeneration. We also conclude that the "white blob" observed at the amputation site by Abrams et al. consists of bacteria and is not regenerated tissue.

Cannabidiol for musculoskeletal regenerative medicine.

Chronic musculoskeletal (MSK) pain is one of the most prevalent causes, which lead patients to a physician's office. The most common disorders affecting MSK structures are osteoarthritis, rheumatoid arthritis, back pain, and myofascial pain syndrome, which are all responsible for major pain and physical disability. Although there are many known management strategies currently in practice, phytotherapeutic compounds have recently begun to rise in the medical community, especially cannabidiol (CBD). This natural, non-intoxicating molecule derived from the cannabis plant has shown interesting results in many preclinical studies and some clinical settings. CBD plays vital roles in human health that go well beyond the classic immunomodulatory, anti-inflammatory, and antinociceptive properties. Recent studies demonstrated that CBD also improves cell proliferation and migration, especially in mesenchymal stem cells (MSCs). The foremost objective of this review article is to discuss the therapeutic potential of CBD in the context of MSK regenerative medicine. Numerous studies listed in the literature indicate that CBD possesses a significant capacity to modulate mammalian tissue to attenuate and reverse the notorious hallmarks of chronic musculoskeletal disorders (MSDs). The most of the research included in this review report common findings like immunomodulation and stimulation of cell activity associated with tissue regeneration, especially in human MSCs. CBD is considered safe and well tolerated as no serious adverse effects were reported. CBD promotes many positive effects which can manage detrimental alterations brought on by chronic MSDs. Since the application of CBD for MSK health is still undergoing expansion, additional randomized clinical trials are warranted to further clarify its efficacy and to understand its cellular mechanisms.

[Low level laser therapy: molecular mechanisms of anti-inflammatory and regenerative effects]. / Nizkointensivnaya lazernaya terapiya: molekulyarnye mekhanizmy protivovospalitel'nogo i regenerativnogo effektov.

Laser therapy as a physiotherapeutic method has been successfully used for a long time in the treatment of various pathologies, but the action mechanisms of low level laser therapy (LLLT) remain understudied. OBJECTIVE: To perform the analysis of published results of LLLT investigations, to describe the physical principles of photobiomodulation, its action mechanisms on various cells and tissues, therapeutic intervention and efficiency of the technique. MATERIAL AND METHODS: The search of articles was done for the period from 2014 to 2022. The preference was given to the articles for the last 5 years in the PubMed database depending on keywords: low level laser therapy, photobiomodulation, exosomes, monocytes, macrophages. RESULTS AND DISCUSSION: This article represents the current conceptions about the action mechanisms and reproduced effects of low level laser therapy, the photobiomodulation influence on the inflammation and reparative processes in human body by intervention on cells and their signal pathways. The discussion of research results and probable causes of conflicting data are performed, as well as the efficacy assessment of laser irradiation in different conditions and diseases is made. CONCLUSION: Laser therapy has certain variety of advantages, among which: non-invasiveness and availability, long-term service of equipment, stable intensity of light radiation and the ability to use in various wavelength ranges. The technique efficacy was proven for a large number of diseases. However, for the successful application of photobiomodulation in clinical practice in current evidence-based medicine, additional investigations are necessary to determine the best dosimetric radiation parameters, as well as further study of action mechanisms on various human cells and tissues.

Aggregating in vitro-grown adipocytes to produce macroscale cell-cultured fat tissue with tunable lipid compositions for food applications.

We present a method of producing bulk cell-cultured fat tissue for food applications. Mass transport limitations (nutrients, oxygen, waste diffusion) of macroscale 3D tissue culture are circumvented by initially culturing murine or porcine adipocytes in 2D, after which bulk fat tissue is produced by mechanically harvesting and aggregating the lipid-filled adipocytes into 3D constructs using alginate or transglutaminase binders. The 3D fat tissues were visually similar to fat tissue harvested from animals, with matching textures based on uniaxial compression tests. The mechanical properties of cultured fat tissues were based on binder choice and concentration, and changes in the fatty acid compositions of cellular triacylglyceride and phospholipids were observed after lipid supplementation (soybean oil) during in vitro culture. This approach of aggregating individual adipocytes into a bulk 3D tissue provides a scalable and versatile strategy to produce cultured fat tissue for food-related applications, thereby addressing a key obstacle in cultivated meat production.

Royal jelly extracellular vesicles promote wound healing by modulating underlying cellular responses.

Apis mellifera royal jelly (RJ) is a well-known remedy in traditional medicine around the world and its versatile effects range from antibacterial to anti-inflammatory properties and pro-regenerative properties. As a glandular product, RJ has been shown to contain a substantial number of extracellular vesicles (EVs), and, in this study, we aimed to investigate the extent of involvement of RJEVs in wound healing-associated effects. Molecular analysis of RJEVs verified the presence of exosomal markers such as CD63 and syntenin, and cargo molecules MRJP1, defensin-1, and jellein-3. Furthermore, RJEVs were demonstrated to modulate mesenchymal stem cell (MSC) differentiation and secretome, as well as decrease LPS-induced inflammation in macrophages by blocking the mitogen-activated protein kinase (MAPK) pathway. In vivo studies confirmed antibacterial effects of RJEVs and demonstrated an acceleration of wound healing in a splinted mouse model. This study suggests that RJEVs play a crucial role in the known effects of RJ by modulating the inflammatory phase and cellular response in wound healing. Transfer of RJ into the clinics has been impeded by the high complexity of the raw material. Isolating EVs from the raw RJ decreases the complexity while allowing standardization and quality control, bringing a natural nano-therapy one step closer to the clinics.

Regenerative medicine for the treatment of chronic low back pain: a narrative review.

Low back pain (LBP) is a common and important clinical problem. In addition to pain, patients are also affected by personal, social, and economic burdens. Intervertebral disc (IVD) degeneration is a common cause of LBP, further increasing the patient's morbidity and medical costs. The limitations of current treatment strategies for long-term pain relief mean that increasing attention has been paid to regenerative medicine. We carried out a narrative review to explore the roles of four types of regenerative medicine for treating LBP: marrow-derived stem cells, growth factors, platelet-rich plasma, and prolotherapy. Marrow-derived stem cells are regarded as an ideal cell source for IVD regeneration. Growth factors may stimulate the synthesis of extracellular matrix and attenuate or reverse the degenerative process in IVD, while platelet-rich plasma, which contains multiple growth factors, is thought to be a promising alternative therapy for IVD degeneration. Prolotherapy can initiate the body's inflammatory healing response to repair injured joints and connective tissues. This review summarizes the mechanisms, in vitro and in vivo studies, and clinical applications of these four types of regenerative medicine in patients with LBP.