Orthopedic Regenerative Medicine Research Articles

Recent trends of stem cell therapies in The management of orthopedic surgical challenges.

Emerged health-related problems especially with increasing population and with the wider occurrence of these issues have always put the utmost concern and led medicine to outgrow its usual mode of treatment, to achieve better outcomes. Orthopedic interventions are one of the most concerning hitches, requiring advancement in several issues, that show complications with conventional approaches. Advanced studies have been undertaken to address the issue, among which stem cell therapy emerged as a better area of growth. The capacity of the stem cells to renovate themselves and adapt into different cell types made it possible to implement its use as a regenerative slant. Harvesting the stem cells, particularly mesenchymal stem cells is easier and can be further grown in vitro. In this review, we have discussed orthopedic-related issues including bone defects and fractures, non-unions, ligament and tendon injuries, degenerative changes, and associated conditions, which require further approaches to execute better outcomes, and the advanced strategies that can be tagged along with various ways of application of mesenchymal stem cells. It aims to objectify the idea of stem cells, with a major focus on the application of Mesenchymal stem cells (MSCs) from different sources in various orthopedic interventions. It also discusses the limitations, and future scopes for further approaches in the field of regenerative medicine. The involvement of mesenchymal stem cells may transition the procedures in orthopedic interventions from predominantly surgical substitution and reconstruction to bio-regeneration and prevention. Nevertheless, additional improvements and evaluations are required to explore the effectiveness and safety of mesenchymal stem cell treatment in orthopedic regenerative medicine.

Sphingolipidomic profiling of human Dental Pulp Stem Cells undergoing osteogenic differentiation

It is now recognized that sphingolipids are involved in the regulation and pathophysiology of several cellular processes such as proliferation, migration, and survival. Growing evidence also implicates them in regulating the behaviour of stem cells, the use of which is increasingly finding application in regenerative medicine. A shotgun lipidomic study was undertaken to determine whether sphingolipid biomarkers exist that can regulate the proliferation and osteogenic differentiation of human Dental Pulp Stem Cells (hDPSCs). Sphingolipids were extracted and identified by direct infusion into an electrospray mass spectrometer. By using cells cultured in osteogenic medium and in medium free of osteogenic stimuli, as a control, we analyzed and compared the SPLs profiles. Both cellular systems were treated at different times (72 hours, 7 days, and 14 days) to highlight any changes in the sphingolipidomic profiles in the subsequent phases of the differentiation process. Signals from sphingolipid species demonstrating clear differences were selected, their relative abundance was determined, and statistical differences were analyzed. Thus, our work suggests a connection between sphingolipid metabolism and hDPSC osteogenic differentiation and provides new biomarkers for improving hDPSC-based orthopaedic regenerative medicine.

Identification of unapproved orthopedic regenerative medicine: Usefulness of the Act on Safety of Regenerative Medicine

In Japan, the Act on Safety of Regenerative Medicine regulates unapproved regenerative medicine. Other nations market regenerative medicine products, bypassing regulatory approval. To identify unapproved orthopedic regenerative medicine, we have used data based on the Act. Platelet-rich plasma was often used. The common target was the knee. Prices averaged $2,490.

Stable Housekeeping Genes in Bone Marrow, Adipose Tissue, and Amniotic Membrane-Derived Mesenchymal Stromal Cells for Orthopedic Regenerative Medicine Approaches.

The therapeutic effect of mesenchymal stromal cells (MSCs) has been described for a variety of disorders, including those affecting musculoskeletal tissues. In this context, the literature reports several data about the regenerative effectiveness of MSCs derived from bone marrow, adipose tissue, and an amniotic membrane (BMSCs, ASCs, and hAMSCs, respectively), either when expanded or when acting as clinical-grade biologic pillars of products used at the point of care. To date, there is no evidence about the superiority of one source over the others from a clinical perspective. Therefore, a reliable characterization of the tissue-specific MSC types is mandatory to identify the most effective treatment, especially when tailored to the target disease. Because molecular characterization is a crucial parameter for cell definition, the need for reliable normalizers as housekeeping genes (HKGs) is essential. In this report, the stability levels of five commonly used HKGs (ACTB, EF1A, GAPDH, RPLP0, and TBP) were sifted into BMSCs, ASCs, and hAMSCs. Adult and fetal/neonatal MSCs showed opposite HKG stability rankings. Moreover, by analyzing MSC types side-by-side, comparison-specific HKGs emerged. The effect of less performant HKG normalization was also demonstrated in genes coding for factors potentially involved in and predicting MSC therapeutic activity for osteoarthritis as a model musculoskeletal disorder, where the choice of the most appropriate normalizer had a higher impact on the donors rather than cell populations when compared side-by-side. In conclusion, this work confirms HKG source-specificity for MSCs and suggests the need for cell-type specific normalizers for cell source or condition-tailored gene expression studies.

DEVELOPMENT OF A DYNAMIC COIL-SHAPED SCAFFOLD FOR ARTICULAR CARTILAGE TISSUE ENGINEERING

Even minor lesions in articular cartilage (AC) can cause underlying bone damage creating an osteochondral (OC) defect. OC defects can cause pain, impaired mobility and can develop to osteoarthritis (OA). OA is a disease that affects nearly 10% of the population worldwide[1], and represents a significant economic burden to patients and society[2]. While significant progress has been made in this field, realising an efficacious therapeutic option for unresolved OA remains elusive and is considered one of the greatest challenges in the field of orthopaedic regenerative medicine[3]. Therefore, there is a societal need to develop new strategies for AC regeneration. In recent years there has been increased interest in the use of tissue-specific aligned porous freeze-dried extracellular matrix (ECM) scaffolds as an off-the-shelf approach for AC repair, as they allow for cell infiltration, provide biological cues to direct target-tissue repair and permit aligned tissue deposition, desired in AC repair[4]. However, most ECM-scaffolds lack the appropriate mechanical properties to withstand the loads passing through the joint[5]. One solution to this problem is to reinforce the ECM with a stiffer framework made of synthetic materials, such as polylactic acid (PLA)[6]. Such framework can be 3D printed to produce anatomically accurate implants[7], attractive in personalized medicine. However, typical 3D prints are static, their design is not optimized for soft-hard interfaces (OC interface), and they may not adapt to the cyclic loading passing through our joints, thus risking implant failure. To tackle this limitation, more compliant or dynamic designs can be printed, such as coil-shaped structures[8]. Thus, in this study we use finite element modelling to create different designs that mimic the mechanical properties of AC and prototype them in PLA, using polyvinyl alcohol as support. The optimal design will be combined with an ECM scaffold containing a tailored microarchitecture mimicking aspects of native AC.Acknowledgments: This project has received funding from the European Union's Horizon Europe research and innovation MSCA PF programme under grant agreement No. 101110000.

Allogenic perinatal tissue for musculoskeletal regenerative medicine applications: a systematic review protocol

BackgroundMusculoskeletal ailments impact the lives of millions of people, and at times necessitate surgery followed by physiotherapy, drug treatments, or immobilization. Regenerative musculoskeletal medicine has undergone enormous progress over the last few decades. Sources of tissues used for regenerative medicine purposes can be grouped into autologous or allogenic. Although autologous sources are promising, there is a wide range of limitations with the treatment, including the lack of randomized controlled studies for orthopaedic conditions, donor site morbidity, and highly variable outcomes for patients. Allogenic sources bypass some of these shortcomings and are a promising source for orthopaedic regenerative medicine applications.MethodsA systematic search will be performed using PubMed, Elsevier, ScienceDirect, and Google Scholar databases for articles published in English before May 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and guidelines will be used. Studies will be eligible if they apply to acute and chronic orthopaedic musculoskeletal complications or animal or human disease models. Publications must include the use of MSCs and/or tissue obtained from amniotic/chorionic membrane, amniotic fluid, umbilical cord, and/or umbilical cord-derived Wharton’s jelly as an intervention. Placebos, noninjury models, acute injury models, non-injury models, and gold standard treatments will be compared. The study selection will be performed by two independent reviewers using a dedicated reference management software. Data synthesis and meta-analysis will be performed separately for preclinical and clinical studies.DiscussionThe results will be published in relevant peer-reviewed scientific journals. Investigators will present results at national or international conferences.Trial registration: The Protocol will be registered on PROSPERO international prospective register of systematic reviews prior to commencement.

Different Sources of Mesenchymal Stem Cells for Tissue Regeneration: A Guide to Identifying the Most Favorable One in Orthopedics and Dentistry Applications.

The success of regenerative medicine in various clinical applications depends on the appropriate selection of the source of mesenchymal stem cells (MSCs). Indeed, the source conditions, the quality and quantity of MSCs, have an influence on the growth factors, cytokines, extracellular vesicles, and secrete bioactive factors of the regenerative milieu, thus influencing the clinical result. Thus, optimal source selection should harmonize this complex setting and ensure a well-personalized and effective treatment. Mesenchymal stem cells (MSCs) can be obtained from several sources, including bone marrow and adipose tissue, already used in orthopedic regenerative applications. In this sense, for bone, dental, and oral injuries, MSCs could provide an innovative and effective therapy. The present review aims to compare the properties (proliferation, migration, clonogenicity, angiogenic capacity, differentiation potential, and secretome) of MSCs derived from bone marrow, adipose tissue, and dental tissue to enable clinicians to select the best source of MSCs for their clinical application in bone and oral tissue regeneration to delineate new translational perspectives. A review of the literature was conducted using the search engines Web of Science, Pubmed, Scopus, and Google Scholar. An analysis of different publications showed that all sources compared (bone marrow mesenchymal stem cells (BM-MSCs), adipose tissue mesenchymal stem cells (AT-MSCs), and dental tissue mesenchymal stem cells (DT-MSCs)) are good options to promote proper migration and angiogenesis, and they turn out to be useful for gingival, dental pulp, bone, and periodontal regeneration. In particular, DT-MSCs have better proliferation rates and AT and G-MSC sources showed higher clonogenicity. MSCs from bone marrow, widely used in orthopedic regenerative medicine, are preferable for their differentiation ability. Considering all the properties among sources, BM-MSCs, AT-MSCs, and DT-MSCs present as potential candidates for oral and dental regeneration.

Finite element analysis of the influence of porosity and pore geometry on mechanical properties of orthopaedic scaffolds

PurposeScaffolds play a key role in regenerative medicine in the repair of injuries, defects and cancerous changes in long bones. For this reason, scaffolds should meet certain mechanobiological requirements, such as adequate porosity and pore geometry to ensure appropriate osteointegration as well as load transfer. Taking into account the most frequently used cell units, this study attempted to evaluate the porous structures of orthopaedic scaffolds in terms of their strength parameters. Materials and methodsFour pore geometries were selected for analyses: sphere, octagonal prism, cube and triangular prism, all with porosities of 10% up to 60%. Three different material properties were considered: Ti6Al4V alloy, CoCr alloy, 316 L steel. Strength compression simulations were carried out on 144 models, 72 structures of cell units with dimensions of 4 × 4 × 4 mm and 72 structures of scaffolds with a diameter of 16 mm and a height of 15 mm. Effective Young's modulus, as well as 0.2%, offset effective yield strength was estimated. ResultsResearch has shown that scaffolds with bone-like strength properties should be made of Ti6Al4V alloy. The value of 40% turned out to be of the best porosity. The remaining porosities showed much lower or much higher strength parameters and were significantly different from the properties of the bones. ConclusionsThe obtained data allow to indicate the most functional porous structure with Young's modulus similar to that possesses by core bone, while maintaining mechanical strength, allowing for its appropriate use in orthopaedic regenerative medicine.

Allogenic Amniotic Tissue for Treatment of Knee and Hip Osteoarthritis.

Osteoarthritis (OA) impacts millions of people and places a high burden on healthcare systems in the United States. Current treatment modalities have limitations and do not address underlying pathology. Lately, there has been an immense growth in the use of biologics, including perinatal allogenic tissues for orthopedic regenerative medicine applications. Amniotic tissue is an exciting new alternative for such applications. Despite several published studies that reported its use for treatment of ophthalmic conditions and complex wounds, there are limited clinical studies evaluating its safety and efficacy in treating patients suffering with knee or hip OA. In this manuscript, I focused on three prospective clinical studies which evaluated the safety and efficacy of amniotic tissue in patients suffering with moderate knee or hip OA. The results from these studies presented the scientific community with much needed, well-executed, and prospective clinical trials. Though these trials demonstrated that administration of amniotic tissue in knee or hip joint is safe and potentially effective, more multi-center, prospective, double-blinded, randomized controlled trials are warranted to further establish the efficacy of amniotic tissue to mitigate symptoms of knee and hip OA to ultimately justify its clinical use.

Bioactive Glass Fiber-Reinforced Plastic Composites Prompt a Crystallographic Lophelia Atoll-Like Skeletal Microarchitecture Actuating Periosteal Cambium.

The touchstone for bone replacing or anchoring trauma implants, besides resorption, includes functional ankylosis at a fixation point and replacement by viable functional neo-bone tissues. These parameters redefined the concept of "resorbability" as "bioresorbability." Interference screws are the most commonly used resorbable anchoring implants for anterior cruciate ligament (ACL) reconstruction (surgery). Over the years, the bioresorbable screw fixation armamentarium has amplified countless choices, but instability and postimplantation complications have raised concerns about its reliability and efficacy. Owing to this interest, in this work, bioactive glass fiber-reinforced plastic (BGFP) composites with (BGFPnb5) and without (BGFP5) niobicoxide composing multiplexed network modifiers are reported as bioresorbable bone-anchoring substitutes. These synergistically designed composites have a fabricated structure of continuous, unidirectional BG fibers reinforced in an epoxy resin matrix using "melt-drawing and microfabrication" technology. The BGFP microarchitecture is comprised of multiplexed oxide components that influence bioactive response in a distinctive lophelia atoll-like apatite formation. Furthermore, it assists in the proliferation, adherence, and migration of bone marrow-derived mesenchymal stem cells. It also exhibits superior physicochemical characteristics such as surface roughness, hydrophilic exposure, distinctive flexural strength, and bioresorption. Thus, it induces restorative bone osseointegration and osteoconduction and actuates periosteum function. In addition, the BGFP influences the reduction of DH5-α Escherichia coli in suspension culture, demonstrating potential antibacterial efficacy. In conclusion, the BGFP composite therapeutic efficacy demonstrates distinctive material characteristics aiding in bone regeneration and restoration that could serve as a pioneer in orthopedic regenerative medicine.

Ilizarov technology and chinese philosophy (To commemorate the 100th anniversary of the birth of Professor Ilizarov)

The Ilizarov technology was honored as a "milestone" in the history of orthopedics in the 20th century, benefiting tens of thousands of patients around the world, including Chinese patients. The paper presents an analysis of the integration of the method into Chinese medicine, taking into account national traditions, culture and clinical thinking. Ilizarov technology has revolutionized the orthopaedic surgery and clinical limb regeneration medicine in China. Ilizarov's methodology arose suddenly and brought about revolutionary changes in terms of theoretical guidance, methods of thinking, tools used and medical procedures. For the first time, Ilizarov's discovery made people realize that the human body, natural selection in biology and joint symbiotic evolutionary characteristics are common, namely, as long as the levers activate the tissue regeneration switch and changes in regulation, any tissue at any age and to any degree can complete the self-healing process in according to the requirements of doctors and the expectations of patients, similar to the growth of children. The process of working with an external Ilizarov fixator is like playing chess and changing a kaleidoscope, and the countless number of free combinations of stress configurations can be changed in accordance with the needs of the treatment. In China, Qin Xihe integrated the Chinese culture into the Ilizarov technology, thus forming the Chinese Ilizarov technology. He proposed new concepts such as the concept of natural reconstruction, evolutionary orthopedics, interpretation of body language, one walk, two lines, the principle of three balances, happy orthopedics, etc., which were introduced into clinical practice in the field of limb deformity correction and functional reconstruction. As of December 31, 2018, 35,075 cases of various deformities and disorders of the limbs were entered into the Qinsihe orthopedic database, of which 8113 cases were treated with external fixation (Ilizarov technology). The statistics of a large number of cases showed striking results: diseases treated with this technique covered almost all sections of orthopedic pathology and more than 10 sections of non-orthopedic and traumatological pathology, including vascular, nervous, genetic, metabolic, and skin diseases. In addition to orthopedic, there are more than 170 diseases in total. When Ilizarov's technology is applied, it can magically transform the old into the young. Therefore it is known as a "lifeboat". Conclusion Over the past 70 years, Ilizarov's ideas and technologies have been preserved, updated and augmented. Ilizarov's technology serves as an evolutionary phenomenon that transcends bone science. If you understand this technique, you will understand the direction of modern orthopedic surgery and regenerative medicine. Professor Ilizarov's morale and the spirit of fighting to alleviate the suffering of patients were transferred to the Chinese medical community. This awakened many Chinese doctors who followed the norms of the old and stereotyped medicine. After celebrating the centenary of the birth of Professor Ilizarov, ASAMI China will also prepare for the “Sixth ASAMI & ILLRS-BR World Conference (Beijing – 2023)”. We believe that orthopedics and allied disciplines around the world have a bright future.

A retrospective analysis of a commercially available platelet-rich plasma kit during clinical use.

Point-of-care analyses of platelet-rich plasma (PRP) are not routine in the orthopedic regenerative medicine field. Therefore, many physicians rely on the manufacturer's reported content for commercial preparation kits. This contributes to a knowledge gap between injectate content and patient outcome. To assess whether the EmCyte PurePRP II 60-mL preparation kit returns PRP content that meets the manufacturer's expectations when used during routine clinical care for a heterogenous patient population, and to determine whether a change in PRP yield volume affects injectate content. Protocol A (exclusion of granulocytes and low hematocrit) and Protocol B (inclusion of granulocytes and higher hematocrit) were evaluated. Retrospective review. Private practice. One hundred five patients (118 preparations) treated for orthopedic conditions over an 8-month period via PRP injection. Thirteen patients had two independently made preparations on different treatment days that qualified for analysis. Not applicable. Complete blood count (absolute counts and calculated fold enrichment from baseline of platelets, white blood cells, red blood cells, granulocytes, lymphocytes, monocytes; and hematocrit levels). Confounding variables included age, gender, and preparation yield volume. During routine clinical use, the cellular content of both Protocols A and B met or exceeded the manufacturer's expectations of platelet enrichment and granulocyte inclusion or exclusion. Hematocrit values were slightly higher than anticipated from Protocol A preparations. The modification of yield volume from 7 to 4mL led to a significant difference in platelet enrichment without affecting absolute cell counts (2.88; 95% confidence interval [CI] 1, 4.76; P=.003). Both gender and age moderately affected the level of platelet enrichment from baseline but did not significantly affect absolute platelet counts. In the absence of widespread characterization, confirming the variation in commercial PRP kits during clinical use is crucial.

Nanomaterial Nitric Oxide Delivery in Traumatic Orthopedic Regenerative Medicine.

Achieving bone fracture union after trauma represents a major challenge for the orthopedic surgeon. Fracture non-healing has a multifactorial etiology and there are many risk factors for non-fusion. Environmental factors such as wound contamination, infection, and open fractures can contribute to non-healing, as can patient specific factors such as poor vascular status and improper immunologic response to fracture. Nitric oxide (NO) is a small, neutral, hydrophobic, highly reactive free radical that can diffuse across local cell membranes and exert paracrine functions in the vascular wall. This molecule plays a role in many biologic pathways, and participates in wound healing through decontamination, mediating inflammation, angiogenesis, and tissue remodeling. Additionally, NO is thought to play a role in fighting wound infection by mitigating growth of both Gram negative and Gram positive pathogens. Herein, we discuss recent developments in NO delivery mechanisms and potential implications for patients with bone fractures. NO donors are functional groups that store and release NO, independent of the enzymatic actions of NOS. Donor molecules include organic nitrates/nitrites, metal-NO complexes, and low molecular weight NO donors such as NONOates. Numerous advancements have also been made in developing mechanisms for localized nanomaterial delivery of nitric oxide to bone. NO-releasing aerogels, sol- gel derived nanomaterials, dendrimers, NO-releasing micelles, and core cross linked star (CCS) polymers are all discussed as potential avenues of NO delivery to bone. As a further target for improved fracture healing, 3d bone scaffolds have been developed to include potential for nanoparticulated NO release. These advancements are discussed in detail, and their potential therapeutic advantages are explored. This review aims to provide valuable insight for translational researchers who wish to improve the armamentarium of the feature trauma surgeon through use of NO mediated augmentation of bone healing.

Numerical Analysis of the Influence of Porosity and Pore Geometry on Functionality of Scaffolds Designated for Orthopedic Regenerative Medicine.

Background: Scaffolds are vital for orthopedic regenerative medicine. Therefore, comprehensive studies evaluating their functionality with consideration of variable parameters are needed. The research aim was to evaluate pore geometry and scaffold porosity influence on first, cell culture efficiency in a perfusion bioreactor and second, osteogenic cell diffusion after its implantation. Methods: For the studies, five pore geometries were selected (triangular prism with a rounded and a flat profile, cube, octagonal prism, sphere) and seven porosities (up to 80%), on the basis of which 70 models were created for finite element analyses. First, scaffolds were placed inside a flow channel to estimate growth medium velocity and wall shear stress. Secondly, scaffolds were placed in a bone to evaluate osteogenic cell diffusion. Results: In terms of fluid minimal velocity (0.005 m/s) and maximal wall shear stress (100 mPa), only cubic and octagonal pores with 30% porosity and spherical pores with 20% porosity fulfilled the requirements. Spherical pores had the highest osteogenic cell diffusion efficiency for porosities up to 30%. For higher porosities, the octagonal prism’s pores gave the best results up to 80%, where no differences were noted. Conclusions: The data obtained allows for the appropriate selection of pore geometry and scaffold porosity for orthopedic regenerative medicine.

Mesenchymal Stem Cells for Orthopedic Treatments and Regenerative Medicine

Mesenchymal Stem Cells for Orthopedic Treatments and Regenerative Medicine

Effects of a Bioactive SPPEPS Peptide on Chondrogenic Differentiation of Mesenchymal Stem Cells.

A synthetic 'chondroinductive' biomaterial that could induce chondrogenesis without the need for growth factors, extracellular matrix, or pre-seeded cells could revolutionize orthopedic regenerative medicine. The objective of the current study was thus to introduce a synthetic SPPEPS peptide and evaluate its ability to induce chondrogenic differentiation. In the current study, dissolving a synthetic chondroinductive peptide candidate (100ng/mL SPPEPS) in the culture medium of rat bone marrow-derived mesenchymal stem cells (rBMSCs) elevated collagen type II gene expression compared to the negative control (no growth factor or peptide in the cell culture medium) after 3days. In addition, proteomic analyses indicated similarities in pathways and protein profiles between the positive control (10ng/mL TGF-β3) and peptide group (100 ng/mL SPPEPS), affirming the potential of the peptide for chondroinductivity. Incorporating the SPPEPS peptide in combination with the RGD peptide in pentenoate-functionalized hyaluronic acid (PHA) hydrogels elevated the collagen type II gene expression of the rBMSCs cultured on top of the hydrogels compared to using either peptide alone. The evidence suggests that SPPEPS may be a chondroinductive peptide, which may be enhanced in combination with an adhesion peptide.

Epigenetics as a New Frontier in Orthopedic Regenerative Medicine and Oncology.

Skeletal regenerative medicine aims to repair or regenerate skeletal tissues using pharmacotherapies, cell-based treatments, and/or surgical interventions. The field is guided by biological principles active during development, wound healing, aging, and carcinogenesis. Skeletal development and tissue maintenance in adults represent highly intricate biological processes that require continuous adjustments in the expression of cell type-specific genes that generate, remodel, and repair the skeletal extracellular matrix. Errors in these processes can facilitate musculoskeletal disease including cancers or injury. The fundamental molecular mechanisms by which cell type-specific patterns in gene expression are established and retained during successive mitotic divisions require epigenetic control, which we review here. We focus on epigenetic regulatory proteins that control the mammalian epigenome at the level of chromatin with emphasis on proteins that are amenable to drug intervention to mitigate skeletal tissue degeneration (e.g., osteoarthritis and osteoporosis). We highlight recent findings on a number of druggable epigenetic regulators, including DNA methyltransferases (e.g., DNMT1, DNMT3A, and DNMT3B) and hydroxylases (e.g., TET1, TET2, and TET3), histone methyltransferases (e.g., EZH1, EZH2, and DOT1L) as well as histone deacetylases (e.g., HDAC3, HDAC4, and HDAC7) and histone acetyl readers (e.g., BRD4) in relation to the development of bone or cartilage regenerative drug therapies. We also review how histone mutations lead to epigenomic catastrophe and cause musculoskeletal tumors. The combined body of molecular and genetic studies focusing on epigenetic regulators indicates that these proteins are critical for normal skeletogenesis and viable candidate drug targets for short-term local pharmacological strategies to mitigate musculoskeletal tissue degeneration. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1465-1474, 2019.

Current Trends in Viral Gene Therapy for Human Orthopaedic Regenerative Medicine.

Viral vector-based therapeutic gene therapy is a potent strategy to enhance the intrinsic reparative abilities of human orthopaedic tissues. However, clinical application of viral gene transfer remains hindered by detrimental responses in the host against such vectors (immunogenic responses, vector dissemination to nontarget locations). Combining viral gene therapy techniques with tissue engineering procedures may offer strong tools to improve the current systems for applications in vivo. The goal of this work is to provide an overview of the most recent systems exploiting biomaterial technologies and therapeutic viral gene transfer in human orthopaedic regenerative medicine. Integration of tissue engineering platforms with viral gene vectors is an active area of research in orthopaedics as a means to overcome the obstacles precluding effective viral gene therapy. In light of promising preclinical data that may rapidly expand in a close future, biomaterial-guided viral gene therapy has a strong potential for translation in the field of human orthopaedic regenerative medicine.

Regenerative rehabilitation: The role of mechanotransduction in orthopaedic regenerative medicine.

Regenerative rehabilitation is an emerging area of investigation that seeks to integrate regenerative medicine with rehabilitation medicine. It is based on the realization that combining these two areas of medicine at an early stage of treatment will produce a better clinical outcome than the traditional linear approach of first administering the elements of regeneration followed, after a delay, by rehabilitation. Indeed, in certain settings, a case can be made for initiating rehabilitation protocols before starting regenerative intervention. This review summarizes the contents of a workshop held during the 2018 annual meeting of the Orthopaedic Research Society. It introduced the concept of regenerative rehabilitation and then provided two orthopaedic examples drawn from the domains of cartilage repair and bone healing. Rehabilitation medicine can supply a variety of physical stimuli, including electrical stimulation, thermal stimulation and mechanical stimulation. Of these, mechanical stimulation has the most obvious relevance to orthopaedics. The mechano-responsiveness of cartilage and bone has been known for a long time, but is poorly understood and has led to only limited clinical application. Improved bioreactor designs that allow multi-axial loading enable new insights into the responsiveness of chondrocytes and chondroprogenitor cells to specific types of load, especially shear. Recent studies on the mechanobiology of bone healing show that modulating the mechanical environment of an experimental osseous lesion by a process of "Reverse Dynamization" soon after injury considerably enhances healing. Future studies are needed to probe the molecular mechanisms responsible for these phenomena and to translate these findings into clinical practice. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1263-1269, 2019.

Morphology and surface topography of Ti6Al4V lattice structure fabricated by selective laser sintering

Abstract Construction of metallic implants with a porous structure that mimics the biomechanical properties of bone is one of the challenges of orthopedic regenerative medicine. The selective laser sintering technique (SLS) allows the production of complex geometries based on three-dimensional model, which offers the prospect of preparing porous metal implants, in which stiffness and porosity can be precisely adjusted to the individual needs of the patient. This requires an interdisciplinary approach to design, manufacturing and testing of porous structures manufactured by selective sintering. An important link in this process is the ability to assess the surface topography of the struts of porous structure. The paper presents a qualitative assessment of the surface morphology based on SEM studies and methodology that allows for quantitative assessment of stereometric structure based on micro-tomographic measurements.