Current Non-Surgical Curative Regenerative Therapies for Knee Osteoarthritis.

Osteoarthritis (OA) is a prevalent musculoskeletal disease affecting middle-aged and elderly individuals, with knee pain as a common complaint. Standard therapy approaches generally attempt to alleviate pain and inflammation, using various pharmacological and non-pharmacological options. However, the efficacy of these therapies in long-term tissue repair remains debated. As an alternative, regenerative medicine offers a promising strategy, with decreased adverse event rates and increasing evidence of safety and efficacy. This review will outline current advances in regenerative medicine for knee OA, emphasizing outpatient clinic-based therapies that use orthobiological and non-biological products. Different strategies based on orthobiologics are discussed as potential regenerative options for the management of knee OA. Cell-free therapies including platelet-rich plasma, autologous anti-inflammatories, exosomes, human placenta extract, and mitochondrial transplantation are discussed, focusing on their potential for cartilage regeneration. Additionally, cell-based therapies with regenerative properties including bone marrow aspirate concentrate, adipose stromal vascular fraction, microfat, nanofat, stem cell therapy, and genetically modified cells as part of orthobiologics, are being investigated. Also, this study is looking into non-biological approaches such as using gold-induced cytokines, extracorporeal shockwave therapy, and ozone therapy. The mechanisms of action, effectiveness, and clinical applications of each therapy are being explored, providing insights into their role in the management of knee OA.

A novel multifunctional chitosan-gelatin/carboxymethyl cellulose-alginate bilayer hydrogel containing human placenta extract for accelerating full-thickness wound healing.

The replication of skin's dermal and epidermal morphology within a full-thickness wound using a bi-layer hydrogel to cater to their distinct needs is a compelling pursuit. Moreover, human placenta extract (HPE), containing a diverse array of bioactive agents, has proven to be effective in promoting the wound healing process and enhancing epidermal keratinocytes. This study presents a multifunctional bi-layer hydrogel incorporating HPE for accelerating full-thickness wound healing through sustained HPE release, inhibition of bacteria invasion, and promotion of cell proliferation. The upper layer of the scaffold, known as the dressing layer, is composed of carboxymethyl cellulose and sodium alginate, serving as a supportive layer for cell proliferation. The under layer, referred to as the regenerative layer, is composed of chitosan and gelatin, providing an extracellular matrix-like, porous, moist, and antibacterial environment for cell growth. The scaffold was optimized to replicate the morphology of the dermal and epidermal layers, with suitable fibroblast infiltration and a pore size of approximately 283µm. Furthermore, the degradation rate of the samples matched the wound healing rate and persisted throughout this period. The sustained HPE release rate, facilitated by the degradation rate, was optimized to reach ~98% after 28 days, covering the entire healing period. The samples demonstrated robust antibacterial capabilities, with bacterial inhibition zone diameters of and 2.63±0.12cm for S. aureus and E. coli, respectively. The biocompatibility of the samples remained at approximately 68.33±4.5% after 21 days of fibroblast cell culture. The in vivo experiment indicated that the HPE@Bilayer hydrogel promotes the formation of new blood vessels and fibroblasts during the early stages of healing, leading to the appropriate formation of granulation tissue and a wound contraction rate of (79.31±3.1)%. Additionally, it resulted in the formation of a thick epidermal layer (keratinization) that effectively covered all the impaired areas, achieving a wound contraction rate of 95.83±6.3% at the late stage of wound healing. Furthermore, immunohistochemistry staining for CD31 and TGF-ß revealed that the HPE@Bilayer group had 22 blood vessels/field and 34%-66% immunoactive cells, respectively, after 14 days of healing. However, by day 21, angiogenesis and TGF-ß expression had declined, demonstrating that the wounds had been successfully treated with minimal scarring.

Human placental extract regulates polarization of macrophages via IRGM/NLRP3 in allergic rhinitis.

Allergic rhinitis (AR) is globally prevalent and its pathogenesis remains unclear. Alternative activation of macrophages is suggested in AR and thought to be involved in natural immunoregulatory processes in AR. Aberrant activation of Nod-like receptor protein 3 (NLRP3) inflammasome is linked with AR. Human placenta extract (HPE) is widely used in clinics due to its multiple therapeutic potential carried by diverse bioactive molecules in it. We aim to investigate the effect of HPE on AR and the possible underlying mechanism. Ovalbumin (OVA)-induced AR rat model was set up and treated by HPE or cetirizine. General manifestation of AR was evaluated along with the histological and biochemical analysis performed on rat nasal mucosa. A proteomic analysis was performed on AR rat mucosa. Mouse alveolar macrophages (MH-S cells) were cultured under OVA stimulation to investigate the regulation of macrophages polarization. The morphological changes and the expression of NLRP3 inflammasome and immunity-related GTPase M (IRGM) in nasal mucosa as well as in MH-S cells were evaluated respectively. The results of our study showed the general manifestation of AR along with the histological changes in nasal mucosa of AR rats were improved by HPE. HPE suppresses NLRP3 inflammasome and the decline of IRGM in AR rats and MH-S cells. HPE regulates macrophage polarization through IRGM/NLRP3. We demonstrated that HPE had protection for AR and the protection is achieved partly through suppressing M1 while promoting M2, the process which is mediated by IRGM via inhibiting NLRP3 inflammasome in AR.

Placental extract suppresses cardiac hypertrophy and fibrosis in an angiotensin II-induced cachexia model in mice.

Cachexia is an intractable metabolic disorder that causes extreme weight loss. It is a symptom of many chronic diseases, including cancer, liver failure, congestive heart failure and chronic kidney disease, and there is as yet no effective treatment. While the mechanisms underlying cachexia are complex, it is often accompanied by elevated angiotensin II (Ang II). Human placental extract (HPE) is a source of numerous biologically active molecules and has been used clinically to treat chronic hepatitis, liver cirrhosis and other chronic diseases. Here, we investigated the effects of HPE in an Ang II-induced cachexia model in mice. HPE treatment preserved both fat mass and lean body mass and suppressed weight loss in the cachexia model, though food intake was unaffected. Ang II infusion also caused cardiac hypertrophy and fibrosis. HPE suppressed these effects as well as Ang II-induced cardiac expression of genes related to heart failure and cardiac remodeling. HPE also reversed Ang II-induced downregulation of mitochondria-related molecules and suppressed cardiac inflammation and oxidative stress. HPE administration may thus be an effective approach to the treatment of cachexia, cardiac hypertrophy and fibrosis.

Chronic migraine-cephalgia related to trigeminal artery: a case report of innovative regenerative approach.

Persistent trigeminal artery (PTA) originates from the posterior bend or lateral wall of the intra-cavernous carotid artery and is the most common occurring type of remnant primitive fetal arteries. In literature, there is limited number of reports on migraine-cephalgia (MC) associated with coexisting PTA. The primitive anastomose arteries that fully belong to the intracranial arterial vascular system are not supposed to perform any supportive functional activity; usually they are subjected to normal biological decay caused by the aging process and metabolic dysfunctions. The hypothesis suggests that these primitive fetal arteries such as PTA may not undergo a fast and structural deterioration but they might be active contributors to a series of mechanisms that can cause a variety of idiopathic complaints. Consequently this would bring a different therapeutic approach other than their surgical removal, which is the accepted option today as a solution for these problems. In this case report, a chronic unilateral MC due to coexisting PTA adjacent to trigeminal nerve is presented. The caliber and location of the PTA was confirmed by a CT-Angiography. The MC treatment was achieved by administration of bio-identical testosterone, human placenta extract (HPE), b-nicotinamide adenine dinucleotide (NADH) and low dose amlopidine.

A systematic review on persistent trigeminal artery, in searching for a therapeutic solution to idiopathic and unresponsive trigeminal nerve inflammations and migraines.

The rarely diagnosed persistent trigeminal artery (PTA) originates from the posterior bend or lateral wall of the intracavernous carotid artery and is the most common occurring type of remnant primitive fetal arteries. Even if PTA is uncommon, information and awareness about it could be of great help for clinicians dealing with cranial vascular imaging and operating this region. In addition, it could give a supporting response to the presence of a wide range of idiopathic and unresponsive disturbs that sometimes are erroneously interpreted and treated. There are very few published scientific reports of coexisting PTA and unilateral trigeminal neuralgia and migraine-cephalgia (MC). In this review we describe few reported and unreported cases regarding the manifestation of unresponsive trigeminal neuralgia and migraine due to the presence of PTA. Patients usually present with a clinical symptomatology with unstable blood hypertension, pain of typical trigeminal neuralgia and MC that cover unilaterally the occipital area over the second and third divisions of the nerve. The outbreaks may often become more severe during physical exertion, stress and hypertension. Angio-MRI may reveal the PTA with an occasional occurrence of parietal cavernoma. We also describe a case of chronic left MC case associated with an adjacent PTA close to the trigeminal nerve position. The size and location of the PTA was confirmed by a CT-Angiography. The MC was safely treated by bio-identical testosterone, human placenta extract (HPE), b-nicotinamide adenine dinucleotide (NADH) and low dose amlopidine. It is hypothesized that these types of primitive anastomose arteries that fully belong to the intracranial arterial vascular system do not perform any supportive functional activity. Nevertheless, they undergo the normal biological decay caused by the aging process and metabolic dysfunctions. Therefore, such primitive fetal arteries as PTA might be subjected not only to a faster structural deterioration but they would actively contribute to a series of mechanisms causing a variety of idiopathic intracranial vascular and structural symptoms. Consequently, this would change the primary therapeutic approach to solve this problem, today represented by surgical removal. Anatomic implications related to treatment procedure are also discussed.

Effect of human placental extract in the management of biofilm mediated drug resistance - A focus on wound management.

Management of infectious wounds, particularly chronic wounds and burn injuries, is a matter of global concern. Worldwide estimates reveal that, billions of dollars are being spent annually for the management of such chronic ailments. Evidently, bacterial biofilms pose a greater problem in the effective management of infection in chronic wounds, since most of the currently available antibiotics are unable to act on the microorganisms residing inside the protected environment of the biofilms. Accordingly, in the present study, we have attempted to evaluate the anti-biofilm properties of human placental extract (PLX) and also other virulence factors that are mediated via the quorum sensing (QS) signalling system. PLX is well known for its anti inflammatory action and it has been shown earlier some anti microbial and enzymatic activity also. PLX was found to produce significant inhibition of biofilm formation and also decreased the levels of pyoverdin and pyocyanin. The microscopic analysis (both light microscopy and atomic force microscopy) of biofilms was also used for substantiating the findings from spectrophotometric (crystal violet estimation) and fluorescence analysis (resazurin uptake). PLX pre-treatment decreased the hydrophobicity of gram-positive and gram negative cells, indicating the effect of placental extract on adherence property of planktonic cell, serving as an indicator for its antibiofilm effect on microorganisms. The reduced extracellular DNA (eDNA) content in biofilm matrix following treatment with PLX also indicates the effectiveness of placenta extract on bacterial adherence, which in turn serves as evidence substantiating the antibiofilm effects of the PLX. Furthermore, PLX was also found to be significantly effective in the in vitro wound biofilm model. Thus the present study, the first of its kind with PLX, establishes the therapeutic benefit of the same particularly in infected wounds, opening up newer avenue for further exploration.