• AO 42-C3
• callus formation
• fracture healing
• intramedullary nailing
• platelet-rich plasma
• tibial shaft fractures

• Bone
• bone healing
• fracture
• fracture-related infection (FRI)
• non-union

• Humans
• Fractures, Ununited/therapy
• Fracture Healing
• Animals
• Fracture Fixation/adverse effects
• Fractures, Bone/therapy
• Biocompatible Materials/therapeutic use

• cell therapy
• endothelial progenitor cells
• fracture
• nonunion
• platelet-rich plasma

• Humans
• Rats
• Animals
• Endothelial Progenitor Cells
• X-Ray Microtomography
• Femur
• Cell- and Tissue-Based Therapy
• Platelet-Rich Plasma

• Orthopedic Trauma Association

• Bone defects
• Bushen Zhongyao Keli
• Osterix; Tonifying kidneys
• Platelet-rich plasma
• Runx2

• Rats
• Male
• Animals
• Rats, Sprague-Dawley
• Core Binding Factor Alpha 1 Subunit/metabolism
• Femur
• Bone Diseases/metabolism
• Gels
• Platelet-Rich Plasma/metabolism
• Kidney
• China
• Bone Regeneration

• 207138215020 Medical Scientific Research Project of Foshan Health Bureau of Guangdong province, China

• Humans
• Biomimetics
• Fracture Healing
• Bone Morphogenetic Protein 2/therapeutic use
• Fractures, Bone/drug therapy
• Transforming Growth Factor beta
• Treatment Outcome
• Recombinant Proteins

• age-related changes
• age-related diseases (ARDs)
• aging
• anti-aging
• inflammaging
• inflammation
• osteoarthritis
• platelet rich plasma (PRP)
• rejuvenation
• senescence

• aneurysmal bone cyst
• calcaneus
• platelet-rich plasma

• bone repair
• composite scaffold
• oyster shell powder
• stingray skin collagen

Regenerative therapy using platelet-rich plasma (PRP), a rich source of growth factors, has become popular in orthopedic sports medicine. Elite athletes prefer PRP therapy for their injured muscles and tendons primarily to avoid the possible risks of surgical treatment. However, the clinical effectiveness of PRP therapy in elite athletes compared to that in non-athletes remains unknown. Therefore, to investigate the effectiveness of PRP therapy in professional athletes (pro-athletes), we focused on the quality of PRP preparations and compared the levels of bioactive molecules between pro-athletes and non-athletes.

PRP was prepared from healthy, non-smoking male professional soccer players (pro-athletes) (n = 22) and non-athletes (VEGF: n = 34, others: n = 38). The levels of TGFβ1, PDGF-BB, VEGF, and PF4 were determined using ELISA kits. Polyphosphate was probed with 4’,6-diamidino-2-phenylindole and monitored using a fluorometer. The body composition of the donors was determined using a bathroom weighing scale.

The levels of TGFβ1 and VEGF were significantly lower in pro-athletes than in non-athletes, whereas PF4 levels were significantly higher in pro-athletes. No significant difference was found in PDGF-BB levels between these groups. Biomolecule levels were not correlated with polyphosphate levels.

TGFβ1, VEGF, and PDGF-BB levels in pro-athletes were not higher than those in non-athletes. These findings suggest that growth factor levels in PRP may not be a predominant determinant of the clinical effectiveness of PRP therapy in pro-athletes. Increased PF4 levels in pro-athletes suggest an immunological function of PRP that may positively influence tissue regeneration.

• Athlete
• Growth factors
• Platelet-rich plasma
• Polyphosphate

• Delayed union
• Headless screw
• Platelet-rich plasma
• Proximal pole
• Scaphoid
• Scaphoid non-union

• Bone Screws
• Fractures, Bone/surgery
• Hand Injuries
• Humans
• Joint Diseases
• Platelet-Rich Plasma
• Retrospective Studies
• Scaphoid Bone/injuries
• Scaphoid Bone/surgery
• Wrist Injuries

• blood product
• bone formation
• cytokines
• sPL
• wound healing

• Cellulosic scaffolds
• Platelet rich plasma
• Tissue regeneration

The wide range of clinical applications and controversial scientific evidence associated with platelet-rich plasma (PRP) therapy in musculoskeletal medicine requires an examination of the most commonly cited studies within this field.

To identify the 50 most cited articles on PRP, assess their study design, and determine any correlations between the number of citations and level of evidence (LoE) or methodological quality.

Cross-sectional study.

The Web of Science database was queried to identify the top 50 most cited articles on PRP in orthopaedic surgery. Bibliometric characteristics, number of citations, and LoE were recorded. Methodological quality was evaluated using the Modified Coleman Methodology Score (MCMS), Methodological Index for Non-randomized Studies (MINORS), and Minimum Information for Studies Evaluating Biologics in Orthopaedics (MIBO). The Pearson correlation coefficient and Spearman correlation coefficient (r_S) were used to determine the degree of correlation between the number of citations or citation density and LoE, MCMS, MINORS score, and MIBO score. Student t tests were performed for 2-group comparisons.

The top 50 articles were published between 2005 and 2016 in 21 journals. The mean number of citations and citation density were 241 ± 94 (range, 151-625) and 23 ± 8, respectively, and the mean LoE was 2.44 ± 1.67, with 15 studies classified as LoE 1. The mean MCMS, MINORS score, and MIBO score were 66.9 ± 12.6, 16 ± 4.7, and 12.4 ± 3.7, respectively. No correlation was observed between the number of citations or citation density and LoE, MCMS, MINORS score, and MIBO score. A significant difference (P = .02) was noted in LoE in articles from the United States (3.56 ± 1.7) versus outside the United States (2 ± 1.5). Seven of the 8 in vivo studies were published between 2005 and 2010, whereas 19 of the 25 clinical outcome investigations were published between 2011 and 2016. Studies that were published more recently were found to significantly correlate with number of citations (r_S = –0.38; P = .01), citation density (r_S = 0.36; P = .01), and higher LoE (r_S = 0.47; P = .01).

The top 50 most cited articles on PRP consisted of high LoE and fair methodological quality. There was a temporal shift in research from in vivo animal studies toward investigations focused on clinical outcomes.

• electrospinning
• immunomodulation
• macrophage polarization
• osteogenesis
• telmisartan

• Animals
• Bone Regeneration
• Cell Differentiation
• Immunomodulation
• Macrophages/metabolism
• Osteogenesis/physiology
• Rats
• Telmisartan/pharmacology
• Tissue Scaffolds

• Platelet-rich plasma
• sesamoid fracture
• stress fracture

• Delayed union
• Fracture healing
• Non-union
• Orthobiologic
• PRP
• Platelet-rich plasma

As a congenital metabolic bone disease caused by defective osteoclastic resorption of immature bone, osteopetrosis is characterized by diffused sclerosis of bones, brittle bones, easy fracturing, narrow medullary canals, and a weak fracture healing ability. At present, clear standards and principles for the treatment of fractures in patients with osteopetrosis are lacking. Non-operative treatment can prevent fracture hematoma and preserve the blood supply to the bone fragments, while being associated with frequent failures and higher mortality rates. Meanwhile, closed reduction and internal fixation with intramedullary nail (CRIF + IMN) approaches can also protect blood supply to the fracture site. However, IMN cannot be used for the vast majority of patients with osteopetrosis due to the narrowing of medullary canals. Thus, open reduction and internal fixation with plate remains the most appropriate surgical method for treating fractures in patients with osteopetrosis, but this approach is complicated by the lack of intramedullary hematopoiesis in such patients. Fracture healing primarily depends on the blood supply to the external periosteum. Open reduction can also easily destroy the periosteum and cause delayed fracture healing or even nonunion; however, CRIF may be the most practical approach. As a result, it would be prudent to solve the difficulty of drilling during the operation and the problem of postoperative nonunion.

In 2018, we treated an adult patient with osteopetrosis presenting with a subtrochanteric fracture. The fracture was fixed using a femoral locking compression plate. Because of delayed consolidation, at 12 mo postoperatively the patient was further treated with platelet-rich plasma (PRP) combined with radial extracorporeal shock wave therapy (rESWT). Antero-posterior and lateral radiographs obtained at the latest follow-up (10 mo) showed that the callus had grown at the original fracture site, and the medial fracture line almost disappeared.

Osteosynthesis remains the first choice of treatment approach for fractures in patients with osteopetrosis, especially peritrochanteric fractures. Preoperative preparation is necessary to avoid risks such as drill bit breakage and iatrogenic fracture during the operation. Moreover, fractures in a patient with osteopetrosis present with a high risk of delayed union and nonunion, which can be potentially cured with PRP + rESWT.

• Osteopetrosis
• Subtrochanteric fracture
• Nonunion
• Platelet-rich plasma
• Radial extracorporeal shock wave therapy
• Case report

• bone marrow concentrate
• bone marrow edema
• bone marrow lesion
• bone substitutes
• intraosseous injection
• mesenchymal stem cells
• osteoarthritis
• platelet-rich plasma (PRP)
• subchondroplasty
• tricalcium phosphate

• Bone Substitutes/administration & dosage
• Bone Substitutes/therapeutic use
• Calcium Phosphates/administration & dosage
• Calcium Phosphates/therapeutic use
• Humans
• Injections, Intra-Articular
• Osteoarthritis, Knee/therapy
• Platelet-Rich Plasma
• Treatment Outcome

We performed a systematic review on the management of patellar fracture nonunion and report a novel suture-based non-metallic fixation technique associated with platelet-rich plasma and mesenchymal stem cell injections in the management of this injury.

A systematic search was performed up to August 2020 in PubMed and Scopus electronic databases of scholarly articles evaluating different surgical techniques used for nonunion of patellar fractures, with no restrictions on language or year of publication. Furthermore, we describe our novel non-metallic suture fixation technique and a patient in whom this technique was applied.

A total of 9 articles were included in the systematic review. Tension band wiring was the most commonly used procedure (62.7%). Nonoperative procedures (8.1%) resulted in nonunion in all patients. The most common complication after open reduction and internal fixation was infection (7.8%). Our patient at the latest follow-up reported full functional recovery and full extension and flexion of the affected knee with no pain and subjectively normal strength.

The management of patella nonunions is still a challenge. The technique reported here can be used in patellar fracture nonunion, as well as in primary patellar fractures.

• Delayed union
• Fracture
• Non-union
• Patella
• Pseudarthrosis
• Pseudoarthrosis

• KOOS
• Lysholm-Tegner
• VAS
• cytokines
• hyperacute serum
• interleukin
• knee osteoarthritis
• matrix metalloprotease

Nonunions remain a significant burden in orthopedics, often afflicting young males of working age. Positive findings have been published using bone marrow aspirate concentrate (BMAC) and platelet-rich fibrin (PRF) for the treatment augmentation of lower limb nonunions. The aim of this study was to investigate if the treatment augmentation with BMAC and PRF can also accelerate the healing of nonunions of the upper limb.

Sixty-eight patients (45 men, 23 women) affected by 75 nonunions of long bones of the upper limb were treated and divided into two groups. The first series was treated with standard surgery alone (group A); afterwards, the second series benefited from standard surgery with the addition of BMAC and PRF applied on lyophilized bone chips. Nonunions were classified radiographically according to the Weber–Cech method and prognostically using the Calori and Moghaddam scores. All patients were radiographically assessed at 1.5, 3, 6, 12, and 24 months of follow-up.

Baseline demographic characteristics did not present differences between groups. No differences were documented in terms of complications (two in group A and three in group B). Significant differences were instead documented in terms of healing time. The first healing signs were observed 1.5 months after surgery in 90.7% of patients in group B and 34.4% of group A (p < 0.0005). At 1.5, 3, 6, and 12 months, a higher radiographic score was found for group B (all p < 0.0005), while no difference was found at final follow-up of 24 months (90.6% of group A and 97.7% of group B achieved radiological healing). Faster healing with BMAC/PRF augmentation was confirmed for all bones, as well as for the subgroup of patients affected by atrophic nonunions (p = 0.001).

This study showed the benefits of restoring both mechanical and biological aspects when addressing nonunions of the long bones of the upper limb. In particular, the association of BMAC and PRF to lyophilized bone chips was safe and able to accelerate healing time. These good results were confirmed for humerus, radius, and ulna sites, as well as for challenging atrophic nonunions of the upper limb.

• autologous bone grafting
• delayed union
• meta-analysis
• non-union
• platelet-rich plasma

Autologous blood-derived products such as platelet-rich plasma (PRP) are widely used to treat musculoskeletal conditions, including knee osteoarthritis (OA). However, the clinical outcomes after PRP administration are often variable, and there is limited information about the specific characteristics of PRP that impact bioactivity and clinical responses. In this study, we aimed to develop an integrative workflow to evaluate responses to PRP in vitro, and to assess if the in vitro responses to PRP are associated with the PRP composition and clinical outcomes in patients with knee OA. To do this, we used a coculture system of macrophages and fibroblasts paired with transcriptomic analyses to comprehensively characterize the modulation of inflammatory responses by PRP in vitro. Relying on patient-reported outcomes and achievement of minimal clinically important differences in OA patients receiving PRP injections, we identified responders and non-responders to the treatment. Comparisons of PRP from these patient groups allowed us to identify differences in the composition and in vitro activity of PRP. We believe that our integrative workflow may enable the development of targeted approaches that rely on PRP and other orthobiologics to treat musculoskeletal pathologies.

• Fracture healing
• Platelet concentrate
• Platelet-rich plasma, PRP
• Platelets

• Bone and Bones
• Fracture Healing
• Fractures, Bone/therapy
• Humans
• Intercellular Signaling Peptides and Proteins
• Platelet-Rich Plasma

• Bone
• Fracture
• Healing
• Natural
• Osteobiologics
• Synthetic

• Fractures, Bone/surgery
• Humans

To develop cost-effective and efficient bone substitutes for improved regeneration of bone defects, heparin-modified mineralized collagen scaffolds were functionalized with concentrated, naturally occurring bioactive factor mixtures derived from adipose tissue, platelet-rich plasma and conditioned medium from a hypoxia-treated human bone marrow-derived mesenchymal stem cell line. Besides the analysis of the release kinetics of functionalized scaffolds, the bioactivity of the released bioactive factors was tested with regard to chemotaxis and angiogenic tube formation. Additionally, functionalized scaffolds were seeded with human bone marrow-derived mesenchymal stromal cells (hBM-MSC) and their osteogenic and angiogenic potential was investigated. The release of bioactive factors from the scaffolds was highest within the first 3 days. Bioactivity of the released factors could be confirmed for all bioactive factor mixtures by successful chemoattraction of hBM-MSC in a transwell assay as well as by the formation of prevascular structures in a 2D co-culture system of hBM-MSC and human umbilical vein endothelial cells. The cells seeded directly onto the functionalized scaffolds were able to express osteogenic markers and form tubular networks. In conclusion, heparin-modified mineralized collagen scaffolds could be successfully functionalized with naturally occurring bioactive factor mixtures promoting cell migration and vascularization.

• MSC secretome
• adipose tissue extract
• bone regeneration
• bone substitute materials
• collagen scaffold
• growth factor
• hypoxia-conditioned medium
• platelet lysates

• PRP
• allogeneic bone
• bone grafts
• large bone defect
• platelet lysate

• PDGF
• Segmental defect
• beta-TCP
• equine bone
• guided bone regeneration
• histomorphometry

• Bone healing
• Fracture
• Non-union
• Platelet-rich plasma (PRP)

• Fracture Healing/physiology
• Fractures, Ununited/therapy
• Humans
• Platelet-Rich Plasma

Investigations are rapidly increasing into products referred to as orthobiologics and their utility in the nonsurgical and surgical treatment of diverse orthopaedic pathology.

Members (599) of the American Orthopaedic Society for Sports Medicine were sent a survey that assessed their usage, motivation for use, and perceived efficacy of the following orthobiologics: leukocyte-rich platelet-rich plasma, leukocyte-poor platelet-rich plasma (PRP-LP), bone marrow aspirate concentrate, amniotic membrane products, adipose-derived mesenchymal stromal cells, and umbilical cord–derived cells. Application of these orthobiologics for the following pathologies was assessed: osteoarthritis, muscle injuries, tendon injuries, ligament injuries, labral injuries, and focal articular cartilage tears.

The survey was completed by 165 respondents (27.5%), of which 66.1% reported using at least one orthobiologic in their practice. Orthobiologic users reported the following: 71.6% are increasing their use, and 23.9% advertise their use. PRP-LP is the most commonly used orthobiologic for 76.1%, with 30% of PRP-LP users reporting use due to competitor utilization. The pathology most commonly treated with orthobiologics is osteoarthritis, for 71.6% of users, who primarily use PRP-LP in the knee joint. Leukocyte-rich platelet-rich plasma is the most popular orthobiologic in muscle, ligament, tendon, and labral injuries, whereas bone marrow aspirate concentrate is most popular for focal articular cartilage injuries. Primary orthobiologic-eligible groups were adults and recreational noncompetitive athletes. More than half (>50%) of orthobiologic users perceived all but umbilical cord–derived cells to be efficacious.

Orthobiologics are used by a significant number of sports medicine physicians and are likely increasing in popularity. Among orthobiologics, platelet-rich plasmas are the most popular, and osteoarthritis is the pathology most likely to be treated. Orthobiologics are sometimes used for reasons other than clinical efficacy, especially competitor utilization, and physicians are disparate in their application of these products.

Extensive bone defects remain a therapeutic challenge necessitating alternative surgical approaches with better outcomes. Can increase the effectiveness of PRP or EGF treatment in surgical treatment of large bone defects with Masquelet technique?

Aim of this study examined potential therapeutic benefits of the Masquelet technique with induced membranes in combination with platelet-rich plasma (PRP) or epidermal growth factor (EGF) in a rat model of segmental femur defect.

Three groups each consisting of 20 Sprague-Dawley rats were defined as follows: EGF group, PRP group, and control group. A femoral bone defect was created and filled with antibiotic embedded polymethyl methacrylate. Half of the animals in each group were sacrificed at week 6 and the pseudo-membranes formed were analyzed. In the remaining half, the cement was removed and the space was filled with autograft. After another 6 weeks, the structures formed were examined radiologically, histologically, and biochemically.

At week 6, both PRP and EGF groups had significantly higher membrane CD31, TGF-beta, and VEGF levels than controls. At week 12, when compared to controls, PRP and EGF groups had significantly higher membrane CD31 levels and the PRP group had significantly higher membrane TGF levels. Regarding bone tissue levels, PRP and EGF groups had significantly higher VEGF levels and the EGF group had significantly higher BMP levels. In addition, PRP and EGF groups had higher radiological scores than controls. However, the two experimental groups did not differ with respect to any parameter tested in this study.

Both PRP and EGF seem to be associated with histological, biochemical, and radiological improvements in experimental rat model of Masquelet technique, warranting in further clinical studies.

Level 5

• Epidermal growth factor (EGF)
• Experimental study
• Femur
• Induced membrane
• Masquelet technique
• Platelet-rich plasma (PRP)

• Animal Shells/metabolism
• Animals
• Bioengineering/methods
• Bone and Bones/metabolism
• Calcium/metabolism
• Calcium Sulfate/chemistry
• Cell Proliferation
• Cells, Cultured
• Interleukin-6/biosynthesis
• Male
• Mesenchymal Stem Cells/cytology
• Microscopy, Electron, Scanning
• Ostreidae/metabolism
• Platelet-Rich Plasma/chemistry
• Porosity
• Rats
• Rats, Sprague-Dawley
• Spectroscopy, Fourier Transform Infrared
• Tissue Engineering/methods
• Tissue Scaffolds
• Tumor Necrosis Factor-alpha/biosynthesis

• Animal models
• Computer simulation
• Data driven models
• Finite element models
• Fracture healing
• Mathematical models
• Mechanism discovery
• Modeling

• cleft palate
• craniofacial
• drug delivery
• polymer scaffold
• regenerative surgery
• tissue engineering

In recent years, the interest in biological treatment of knee lesions has increased, especially the application of platelet-rich plasma is of particular note. The number of articles evaluating platelet-rich plasma (PRP) efficacy in the recovery of knee disorders and during knee surgery has exponentially increased over the last decade. A systematic review with meta-analyses was performed by assessing selected studies of local PRP injections to the knee joint. The study was completed in accordance with 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A multistep search of PubMed, Embase, Cochrane Database of Systematic Reviews, and Clinicaltrials.gov was performed to identify studies on knee surgery and knee lesion treatment with PRP. Of the 4004 articles initially identified, 357 articles focusing on knee lesions were selected and, consequently, only 83 clinical trials were analyzed using the revised Cochrane risk-of-bias tool to evaluate risk. In total, seven areas of meta-analysis reported a positive effect of PRP. Among them, 10 sub-analyses demonstrated significant differences in favor of PRP when compared to the control groups (p < 0.05). This study showed the positive effects of PRP, both on the recovery of knee disorders and during knee surgery; however further prospective and randomized studies with a higher number of subjects and with lower biases are needed.

• PRP
• anterior cruciate ligament (ACL)
• arthroscopy
• knee lesion
• meniscal repair
• meniscus
• osteoarthritis
• osteoarthritis (OA)
• platelet-rich plasma
• tendinopathy
• total knee arthroplasty

• genetic manipulation
• hypoxia
• inflammation
• mesenchymal stem cell
• mesenchymal stromal cell
• preconditioning

• Bone defect
• Bone nonunion
• Bone transport
• Distraction osteogenesis
• Free vascularized grafts
• Ilizarov method
• Induced membrane technique complication

• chemokines
• cytokines
• inflammation
• osteoarthritis
• platelet rich plasma
• release kinetics
• synovial fibroblasts
• tissue repair

• alginate
• biofunctionalization
• biomaterial characterization
• intervertebral disc
• platelet-rich plasma

• Growth factor delivery
• Microgels
• Platelet lysate

• Blood Platelets/cytology
• Drug Carriers/chemistry
• Drug Liberation
• Humans
• Hyaluronic Acid/chemistry
• Microgels/chemistry
• Tissue Engineering

One option to fight joint degradation and inflammation in osteoarthritis is the injection of activated blood products into the synovial space. It has been demonstrated that hyperacute serum is the most proliferative among plasma products, so we investigated how the cytokine milieu of osteoarthritic knee joint reacts to hyperacute serum treatment in vitro. Cartilage, subchondral bone, and synovial membrane explanted from osteoarthritic knees were stimulated by interleukin-1 beta (IL-1β) and the concentration of 39 biomarkers was measured in the co-culture supernatant after hyperacute serum treatment. The IL-1β stimulation triggered a strong inflammatory response and enhanced the concentrations of matrix metalloproteinase 3 and 13 (MMP-3 and MMP-13), while hyperacute serum treatment reduced inflammation by decreasing the concentrations of IL-1β, tumor necrosis factor alpha (TNF-α), interleukin-6 receptor alpha (IL-6Rα), and by increasing the level of interleukin-1 antagonist (IL-1RA) Cell viability increased by day 5 in the presence of hyperacute serum. The level of MMPs-1, 2, and 9 were higher on day 3, but did not increase further until day 5. The concentrations of collagen 1 alpha 1 (COL1A1) and osteonectin were increased and receptor activator of nuclear factor kappa-B ligand (RANKL) was reduced in response to hyperacute serum. We concluded that hyperacute serum treatment induces cell proliferation of osteoarthritic joint tissues and affects the cytokine milieu towards a less inflamed state.

• bone remodeling
• hyperacute serum
• inflammatory cytokines
• knee osteoarthritis
• matrix metalloproteases

• Adult
• Cartilage/drug effects
• Cartilage/pathology
• Coculture Techniques
• Cytokines/metabolism
• Female
• Humans
• Interleukin-1beta/pharmacology
• Knee Joint/drug effects
• Knee Joint/metabolism
• Knee Joint/pathology
• Male
• Middle Aged
• Osteoarthritis, Knee/therapy
• Synovial Membrane/drug effects
• Tissue Culture Techniques
• Young Adult

• Biomaterial
• Biomimetic
• Bone
• Bone targeting
• Delivery
• Repair

• Biocompatible Materials/chemistry
• Biocompatible Materials/pharmacokinetics
• Biocompatible Materials/therapeutic use
• Bone Regeneration/drug effects
• Delayed-Action Preparations/chemistry
• Delayed-Action Preparations/pharmacokinetics
• Delayed-Action Preparations/therapeutic use
• Drug Carriers/chemistry
• Drug Carriers/pharmacokinetics
• Drug Carriers/therapeutic use
• Humans
• Osteoporosis/drug therapy
• Osteoporosis/metabolism
• Osteoporosis/pathology
• Tissue Distribution

• R01 AR063184 NIAMS NIH HHS
• R01 AR071552 NIAMS NIH HHS

Non-union of bone following fracture is an orthopaedic condition with a high morbidity and clinical burden. Despite its estimated global prevalence of nine million annually, the limit of bone regeneration therapy still results in patients living with pain, a reduced quality of life and associated psychological, social and financial repercussions. This review provides an overview of the current epidemiological and aetiological data, and highlights where the clinical challenges in treating non-union lie. Current treatment strategies are discussed as well as promising future research foci. Development in biotechnologies to treat non-union provides exciting scope for more effective treatment for this debilitating condition.

• biotechnologies
• bone
• bone healing
• fracture
• non-union

• Bone morphogenetic proteins
• Gene therapy
• Mesenchymal stem cell transplantation
• Non-unions
• Osteogenesis

• Bone Morphogenetic Proteins
• Bone Transplantation
• Fracture Healing
• Fractures, Bone
• Humans
• Transplantation, Autologous