Abstract. Objectives. The development of promising therapeutics for cartilage repair/regeneration have been hampered by the inadequacy of existing animal models and lack of suitable translational ex-vivo human tissue models. There is an urgent unmet need for these to assess repair/regenerative (orthobiologic) treatments directly in human tissue. We describe methodology allowing the successful long-term ex-vivo culture of non-degenerate whole human femoral heads that may be used as a model for testing new orthobiologic therapies. Methods. Fifteen fresh, viable human femoral heads were obtained from 15 patients (with ethical permission/consent) undergoing hemiarthroplasty for hip fracture, and cultured aseptically (37°C) for up to 10wks. Culture conditions included static/stirred standard media (Dulbecco's modified Eagle's medium; DMEM) and supplementation with 10% human serum (HS). Chondrocyte viability, density, cell morphology, cell volume, glycosaminoglycan(GAG)/collagen content, surface roughness and cartilage thickness were quantified over time. Results. Chondrocyte viability remained highest (>95%;P<0.01;N(n)=3(12)) under static culture conditons in DMEM+10%HS and was maintained over 10wks. In static DMEM culture without 10%HS, viability remained high for ∼4wks, then decreased rapidly (N(n)=4(16)). Chondrocyte viability declined to <35% over 10wks under all other conditions (N(n)=4(16)). Culturing femoral heads in optimal media (DMEM+10%HS) for 10wks increased the number of chondrocytes producing cytoplasmic processes (P<0.002), but decreased cartilage thickness (P<0.002) and GAG content (P=0.028). Cartilage surface roughness, cellular density, chondrocyte volume and collagen content remained unchanged (P>0.05). Conclusions. The viability of human femoral head articular cartilage could be maintained over 10wks in ex-vivo culture. The model may allow testing of a wide range of orthobiologic therapies directly in human tissue, paving the way for subsequent targeted clinical studies of laboratory-proven strategies with the potential to repair/regenerate articular cartilage. Funder. Chief Scientist's Office, Scotland (Grant TCS/18/01). Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Aims. The aim of this study was to establish consensus statements on the diagnosis, nonoperative management, and indications, if any, for medial patellofemoral complex (MPFC) repair in patients with patellar instability, using the modified Delphi approach. Methods. A total of 60 surgeons from 11 countries were invited to develop consensus statements based on their expertise in this area. They were assigned to one of seven working groups defined by subtopics of interest within patellar instability. Consensus was defined as achieving between 80% and 89% agreement, strong consensus was defined as between 90% and 99% agreement, and 100% agreement was considered to be unanimous. Results. Of 27 questions and statements on patellar instability, three achieved unanimous consensus, 14 achieved strong consensus, five achieved consensus, and five did not achieve consensus. Conclusion. The statements that reached unanimous consensus were that an assessment of physeal status is critical for paediatric patients with patellar instability. There was also unanimous consensus on early mobilization and resistance training following nonoperative management once there is no apprehension. The statements that did not achieve consensus were on the importance of immobilization of the knee, the use of orthobiologics in nonoperative management, the indications for MPFC repair, and whether a vastus medialis oblique advancement should be performed. Cite this article: Bone Joint J 2023;105-B(12):1259–1264

Introduction: In many cases of massive rotator cuff tears, especially in cases of revision repairs the shoulder surgeon is facing a technical and biological challenge. The loss of collagenous material in the tendon, coupled with poor quality of the remaining rotator cuff, makes obtaining a mechanically strong repair difficult. Primary closure of such defects may result in excessive tissue tension, which may further increase the chance of failure. Purpose: The objective of this study is to determine the feasibility of using xenogeneic small intestine submucosa (SIS) as a biomaterial to reinforce repair of massive rotator cuff tears. Clinical Material and Methods: Nine patients ranging in age from 52 to 74 with massive rotator cuff tears were selected for the study. Selection of these patients was based upon the quality of remaining rotator cuff tendon tissue at the time of the repair. Seven cases after failed repair of massive rotator cuff tear and two cases of long standing neglected rotator cuff tears in patients with weight bearing shoulders (bilateral below the knees amputation and incomplete paraplegia after anterior poliomyelitis) were selected for this study. In all patients first the tear was repaired by well-known techniques: tendon to tendon, tendon to bone through bone tunnels or using suture anchors. After the repair was accomplished, the poor quality tissue obtained was reinforced by a patch of Restore Orthobiologic Soft Tissue Implant (DePuy, Johnson & Johnson). The Restore Implant is a xenograft obtained of ten layers of porcine small intestine submucosa, it is biocompatible, infection resistant, possess predictable mechanical properties, and, perhaps most significantly, induce a host connective and epithelial tissue response that results in regeneration of specialized connective tissues. Results: Follow-up ranging between 6 to 22 month excellent and good results were observed in eight cases (88%), whereas in the patient aged 74, the cuff repair failed again (after two previous failures). In the eight successful cases an almost normal painfree active range of movements was observed three month after surgery. Conclusions: The results confirm the usefulness of the SIS graft material in the patients having questionable quality cuff tissue remaining after repair. Use of the Restore soft tissue implant could possibly be utilized to strengthen the repair, as well as the inside ingrowth of the tendon, leading to a successful repair of the rotator cuff

Geriatric syndromes could lead individuals to exhibit significant mobility and psychological deficits resulting in significant healthcare costs. Thus, identifying strategies to delay aging, or prevent progressive loss of tissue homeostasis could dramatically restore the function and independence of millions of elderly patients and significantly improve quality of life. One of the fundamental properties of aging is the accumulation of senescent cells and senescence associated secretory phenotypes (SASPs) that needs to be treated in wide range of therapeutics including orthobiologics. Senolytic compounds selectively target and kill senescent cells and inhibit anti-apoptotic pathways that are upregulated in senescent cells thereby inducing apoptotic cell death and abrogating systemic SASP factors. We have also shown that blocking fibrosis with Losartan (TGF-β1 blocker) can improve musculoskeletal healing and cartilage repair by reducing the amount of fibrosis. Thus, we hypothesize that administration of anti-fibrotic agents will enhance the beneficial effects of orthobiologics. The safety and efficacy of several senolytic and anti-fibrotic agents to delay age-related dysfunction and improve the function of orthobiologics have been demonstrated in a variety of animal models (in vivo). Overall, our innovative approaches target senescent cells (inflammation) and TGF-β1 (fibrosis) to enhance the clinical efficacy and use of orthobiologics for musculoskeletal repair. We will also discuss ongoing active clinical trials on orthobiologics to aiming at evaluating the safety and efficacy of senolytic agent (Fisetin) and anti-fibrotic agent (Losartan), used independently or in combination, to enhance the beneficial effects of orthobiologics for patients afflicted with musculoskeletal diseases and conditions

Disease modifying approaches are commonly applied in OA patients. An aging society with better life expectancies is increasing in Europe and the globe. Orthobiologics cover intraarticular hyaluronan injections and also cellular therapies. Cellular therapies range from platelet rich plasma (PRP) applications to exosomes. Short term follow-up of limited number of patients revealed favorable results in clinical cellular therapies. Most of these studies evaluated decrease of pain and increase in function. Recent basic science studies focused on the action mechanism of orthobiologic therapies however patient perspective is less studied. Our research team has recently performed a qualitative study on the patient perspective of hyaluronan injection of the knee joint. Findings of that study will be shared and future patient knowledge based options on orthobiologics will be discussed

Due to the presence of megakaryocytes, platelets and clotting factors, bone marrow aspirate (BMA) tends to coagulate. For the first time, starting from our previous studies on mesenchymal vertebral stem cells, it has been hypothesized that coagulated BMA represents a safe and effective autologous biological scaffold for bone regeneration in spinal surgery. The present research involved advanced preclinical in vitro models and the execution of a pilot clinical study. Evaluation of cell morphology, growth kinetics, immunophenotyping, clonogenicity, trilineage-differentiation, growth-factors and HOX and TALE gene expression were analyzed on clotted- and un-clotted human V-BMA. In parallel, a pilot clinical study on ten patients with degenerative spine diseases submitted to instrumented posterior arthrodesis, is ongoing to assess the ability of clotted-V-BMA to improve spinal fusion at 6- and 12-months follow-up. Results demonstrated that clotted-V-BMA have significantly higher growth-factor expression and mesenchymal stem cell (MSCs) viability, homogeneity, clonogenicity, and ability to differentiate towards the osteogenic phenotype than un-clotted-V-BMA. Clotted-V-BMA also highlighted significant reduced expression of PBX1 and of MEIS3 genes negatively involved in osteoblast maturation and differentiation. From December 2020, eight patients have already been enrolled with first promising results that will be finally evaluated in the next two months. The application of V-BMA-clot as carrier of progenitors and cytokines and as natural scaffold with a structural texture represents a point-of-care orthobiologic product to improve spinal fusion. Clinical application seems to be efficacy, and we will confirm and strengthen these data with the final results of the pilot clinical study

Introduction. Osteochondral lesions (OCLs) of the talus are a challenging and increasingly recognized problem in chronic ankle pain. Many novel techniques exist to attempt to treat this challenging entity. Difficulties associated with treating OCLs include lesion location, size, chronicity, and problems associated with potential graft harvest sites. Matrix associated stem cell transplantation (MAST) is one such treatment described for larger lesions >15mm2 or failed alternative therapies. This cohort study describes a medium-term review of the outcomes of talar lesions treated with MAST. Methods. A review of all patients treated with MAST by a single surgeon was conducted. Preoperative radiographs, MRIs and FAOS outcome questionnaire scores were conducted. Intraoperative classification was undertaken to correlate with imaging. Postoperative outcomes included FAOS scores, return to sport, revision surgery/failure of treatment and progression to arthritis/fusion surgery. Results. 58 MAST procedures in 57 patients were identified in this cohort. The mean follow up was 5 years. There were 20 females and37males, with a mean age of 37 years (SD 9.1). 22 patients had lateral OCLS were and 35 patients had medial OCLs. Of this cohort 32patients had previous surgery and 25 had this procedure as a primary event. 15 patients had one failed previous surgery, 9 patients had two, four patients had three previous surgeries and three patients had four previous surgeries. 12 patients had corrective or realignment procedures at the time of surgery. In terms of complications 3 patients of this cohort went on to have an ankle fusion and two of these had medial malleolar metal work taken out prior to this, 5 patients had additional procedures for arthrofibrotic debridements, 1 patient had a repeat MAST procedure, 1 additional patients had removal of medial malleolar osteotomy screws for pain at the osteotomy site, there were 2 wound complications one related to the ankle and one related to pain at the iliac crest donor site. Conclusion. MAST has demonstrated positive results in lesions which prove challenging to treat, even in a “ failed microfracture” cohort. RCT still lacking in field of orthobiologics for MAST. Longer term follow up required to evaluate durability

Deriving autologous mesenchymal stem cells (MSCs) from adipose tissues without using enzymes requires sophisticated biomedical instruments. Applied pressure on tissues and cells are adjusted manually although centrifugation and filtration systems are frequently used. The number of derived MSCs therefore could differ between instruments. We compared the number of MSCs obtained from four commercially available devices and our newly designed and produced instrument (A2, B3, L3, M2 and T3). Three-hundred mL of adipose tissue was obtained from a female patient undergoing liposuction using the transillumination solution. Obtained tissue was equally distributed to each device and handled according to the producers' guides. After handling, 3 mL stromal vascular fraction (SVF) was obtained from each device. Freshly isolated SVF was characterized using multi-color flow cytometry (Navios Flow Cytometer, Beckman Coulter, USA). Cell surface antigens were chosen according to IFATS and ISCT. CD31-FITC, CD34-PC5,5, CD73-PE, CD90-PB and CD45-A750 (Backman Coulter, USA) fluorochrome-labeled monoclonal antibodies were assessed. Markers were combined with ViaKrome (Beckman Coulter, USA) to determine cell viability. At least 10. 5. cells were acquired from each sample. A software (Navios EX, Beckman Coulter, USA) was used to create dot plots and to calculate the cell composition percentages. The data was analyzed in the Kaluza 2.1 software package (Beckman Coulter, USA). Graphs were prepared in GraphPad Prism. CD105 PC7/CD31 FITC cell percentages were 23,9%, 13,5%, 24,6%, 11,4% and 28,8% for the A2, B3, L3, M2 and T3 devices, respectively. We conclude that the isolated MSC percentage ranged from 11,4% to 28,8% between devices. The number of MSCs in SVF are key determinants of success in orthobiological treatments. Developing a device should focus on increasing the number of MSCs in the SVF while preserving its metabolic activity. Acknowledgments: Scientific and Technological Research Council of Türkiye (TÜBİTAK)- Technology and Innovation Funding Program Directorate (TEYDEB) funded this project (#321893). Servet Kürümoğlu and Bariscan Önder of Disposet Ltd., Ankara, Türkiye (. www.disposet.com. ) contributed to the industrial design and research studies. Ali Tuncel and Feza Korkusuz are members of the Turkish Academy of Sciences (TÜBA). Nilsu Baysal was funded by the STAR Program of TÜBITAK Grant # 3210893

Background. Subtalar nonunion has a detrimental effect on patients' function, and pose a significant challenge for surgeons particularly in the setting of higher risk factors. Methods. We retrospectively analyzed a consecutive series of 49 subtalar nonunions between October 2001 and July 2013. Patient records and radiographs were reviewed for specific patient demographics and comorbidities, subsequent treatments, revision fusion rate, use of bone graft, complications, and clinical outcome. Results. Forty-nine patients with a mean age of 49 years (range 23–80) were included. Sixteen (32%) were heavy smokers (>1 pack per day) and five (10%) had diabetes. Forty one (84%) of the nonunions were symptomatic and underwent a revision procedure at a mean of 16 months (range 2.8 to 57) from the time of the primary arthrodesis. Four of these patients required a triple arthrodesis at the time of revision. Bone graft was used in all cases, and in 25 cases (61%) additional adjuvant orthobiologics. Thirty-two (78%) of the patients achieved a solid arthrodesis at a mean of 3.4 months (range 1.4 to 7.6). Patients who were diabetic and smokers as a group had a 68% rate of union. Of the nine nonunions following a revision arthrodesis, five were in the setting of a prior ankle arthrodesis, three were complicated by a deep infection, and one had no obvious risk factors. Four of the repeat nonunions elected to not undergo an additional procedure, two had a successful third attempt at arthrodesis, one had an additional nonunion followed by a successful fourth attempt at arthrodesis, one had a successful tibiotalocalcaneal arthrodesis, and one ultimately required a below-knee amputation. Discussion. Management of subtalar nonunions pose a significant challenge with a low rate of arthrodesis at 78% fusion rate, but which can be achieved with rigid fixation and utilization of bone graft and orthobiologics

Summary. The BMP-2 content and bone forming potential of 2 leading allograft products (OsteoAMP® and Osteocel® Plus) was tested across 3 commercially available lots. Surprisingly, there was no BMP-2 content associated with the cells contained within Osteocel® Plus. OsteoAMP® contained greater than 1000 times the overall BMP-2 content than Osteocel® Plus. Correspondingly, Osteocel® Plus did not form new bone at any timepoint in the 12 week in vivo study while OsteoAMP® had increasing new bone formation at each sequential timepoint. Interestingly, the highest cellularity of Osteocel® Plus was just prior to implant at t. 0. , decreasing at each timepoint, decreasing further at the terminal endpoint of the study at 12 weeks (82% of cells had died or migrated). Conversely, the cellularity of OsteoAMP® increased at each timepoint. Introduction. Implants containing living cells are often characterised by the orthobiologics industry as ‘osteogenic’. The positive function and ultimate fate of these cells has been assumed with little to no proof of efficacy. In this study we compare the bone forming ability of the market leading stem cell product claiming osteoinductivity as well as osteogenicity, Osteocel® Plus, against the market leading allograft derived growth factor product, OsteoAMP® which claims osteoinductivity but contains no viable cells. The goal of the study is to determine if a cellular product will form new bone or produce a false positive when evaluated histomorphometrically using an osteoinductive control over time in vivo. Additionally, the osteoinductive potential from each product will be quantified by in vitro by measurement of BMP-2 content via ELISA. Methods. Three different lots of each OsteoAMP® and Osteocel® Plus were implanted by an independent lab into muscle pouches of athymic rats. Implants were assessed for bone formation using H&E histology at time of implant, 1 day, 2w, 4w, 6w, 8w, and 12w. Histomorphometric measurements were done using Image J (NIH) using four sections per implant per timepoint (n=12). Each lot of both products was also digested in water, hydrochloric acid, and guanidine-hydrochloride (Gua-HCl) to facilitate BMP-2 content quantification via ELISA (R&D Systems). The extracts were intended to independently measure cellular, mineral, and collagen phase content of BMP-2. All extracts were analyzed by ELISA independently to characterise the source of osteoinductivity and the resulting release profile in vivo. Results. With each subsequent timepoint, all lots of Osteocel® Plus exhibited increasing osteonecrosis with increasing time. By the terminal 12 week timepoint used in this study, 82% of living bone that was implanted for Osteocel® Plus had died or migrated away from the implant site. In contrast, new bone formation and cellularity increased with OsteoAMP® at each timepoint, still increasing at the terminal 12 week endpoint of this study. The BMP-2 results support the bone formation in vivo. Neither of the 3 Osteocel® Plus lots registered any BMP-2 from the cells on ELISA, nor was there any free BMP-2 that leached out of the product. The mineral phase of Osteocel® Plus exhibited traces of BMP-2 for only one of the 3 donors with an average of 0.04 ng/g for all three donors. The protein phase of Osteocel® Plus had the highest concentration of BMP-2 at 0.63 ng/g BMP-2. For all three lots, OsteoAMP® showed no leaching of BMP-2 after exposure to water and a BMP-2 content in the mineral phase of 50.85 ng/g. The collagen phase of OsteoAMP® had the highest concentration of BMP-2 in all groups tested at 915.54 ng/g. Discussion. The results in this study would suggest that orthobiologic implants that contain living cells and claim osteogenic properties do not maintain viable cells over time and did not form bone. Similarly, the results would indicate the living cells do not contribute to osteoinductivity. In contrast, the higher BMP-2 content and osteoinductive property exhibited by OsteoAMP® was a stronger producer of new bone

Surgical repair of rotator cuff tears have high failure rates (20–70%), often due to a lack of biological healing. Augmenting repairs with extracellular matrix-based scaffolds is a common option for surgeons, although to date, no commercially available product has proven to be effective. In this study, a novel collagen scaffold was assessed for its efficacy in augmenting rotator cuff repair. The collagen scaffold was assessed in vitro for cytocompatability and retention of tenocyte phenotype using alamarBLUE assays, confocal imaging and real-time PCR. Immunogenicity was assessed in vitro by the activation of pre-macrophage cells. In vivo, using a modified rat rotator cuff defect model, supraspinatus tendon repairs were carried out in 46 animals. Overlay augmentation with the collagen scaffold was compared to unaugmented repairs. At 6- and 12-weeks post-op the repairs were tested biomechanically to evaluate repair strength, and histologically for quality of healing. The collagen scaffold supported human tenocyte growth in vitro, with cells appearing morphologically tenocytic and expressing higher tendon gene markers compared to plastic controls. No immunogenic responses were provoked compared to suture material control. In vivo, augmentation with the scaffold improved the histological scores at 12 weeks (8.37/15 vs. 6.43/15, p=0.0317). However, no significant difference was detected on mechanical testing. While the collagen scaffold improved the quality of healing of the tendon, a meaningful increase in biomechanical strength was not achieved. This is likely due to its inability to affect the bone-tendon junction. Future materials/orthobiologics must target both the repaired tendon and the regenerating bone-tendon junction

Rotator cuff tears are common in middle-aged and elderly patients. Despite advances in the surgical repair of rotator cuff tears, the rates of recurrent tear remain high. This may be due to the complexity of the tendons of the rotator cuff, which contributes to an inherently hostile healing environment. During the past 20 years, there has been an increased interest in the use of biologics to complement the healing environment in the shoulder, in order to improve rotator cuff healing and reduce the rate of recurrent tears. The aim of this review is to provide a summary of the current evidence for the use of forms of biological augmentation when repairing rotator cuff tears.

Cite this article: Bone Joint J 2024;106-B(9):978–985.

Aims

Platelet-rich plasma (PRP) intra-articular injections may provide a simple and minimally invasive treatment for early-stage knee osteoarthritis (OA). This has led to an increase in its adoption as a treatment for knee OA, although there is uncertainty about its efficacy and benefit. We hypothesized that patients with early-stage symptomatic knee OA who receive multiple PRP injections will have better clinical outcomes than those receiving single PRP or placebo injections.

Bone is a dynamic organ with remarkable regenerative properties seen only otherwise in the liver. However, bone healing requires vascularity, stability, growth factors, a matrix for growth, and viable cells to obtain effective osteosynthesis. We rely on these principles not only to heal fractures, but also achieve healing of benign bone defects. Unfortunately we are regularly confronted with situations where the local environment and tissue is insufficient and we must rely on our “biologic tool box.” When the process of bone repair requires additional assistance, we often look to bone grafting to provide an osteoconductive, osteoinductive, and/or osteogenic environment to promote bone healing and repair. The primary workhorses of bone grafting include autogenous bone, cadaver allograft, and bone graft substitutes. Among the first types of bone graft used and still used in large quantities today include autogenous and cadaver allograft bone. Allografts are useful because it is present in multiple forms that conform to the desired situation. But autogenous bone graft is considered the gold standard because it possesses all the fundamental properties to heal bone. However, it has been associated with high rates of donor site morbidity and typically requires an inpatient hospitalization following the procedure only adding to the associated costs. The first bone graft substitute use was calcium sulfate in 1892, and over the past 122 years advancements have achieved improved material properties of calcium sulfate and helped usher in additional bioceramics for bone grafting. Today there are predominantly four types of bioceramics available, which include calcium sulfate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. They come in multiple forms ranging from pellets and solid blocks to injectable and moldable putty. In comparison to autogenous bone graft, the primary limitation of bioceramics are the lack of osteogenic and osteoinductive properties. Bioceramics work by creating an osteoconductive scaffold to promote osteosynthesis. The options of bone graft substitutes don't end with these four types of bioceramics. Composite bioceramics take advantage of the differing biomechanical properties of these four basis types of bioceramics to develop improved materials. To overcome the lack of osteoinductive and osteogenic properties growth factors or bone marrow aspirate can be added to the bioceramic. As a result, the list of combinations available in our “biologic tool box” continues to expand. More than 20 BMPs have been identified, but only BMP-2 and BMP-7 have FDA approval. As we look forward to areas of future research and need within orthobiologics, some will likely come in the near future while others are much further in the future. We will continue to strive for the ideal bone graft substitute, which will have similar osteoinductive properties as autograft. The ultimate bone graft substitute will likely involve stem cells because it will allow an alternative to autogenous bone with the same osteogenic potential

Bone is a dynamic organ with remarkable regenerative properties seen only otherwise in the liver. However, bone healing requires vascularity, stability, growth factors, a matrix for growth, and viable cells to obtain effective osteosynthesis. We rely on these principles not only to heal fractures, but also achieve healing of benign bone defects. Unfortunately, we are regularly confronted with situations where the local environment and tissue is insufficient and we must rely on our “biologic tool box.” When the process of bone repair requires additional assistance, we often look to bone grafting to provide an osteoconductive, osteoinductive, and/or osteogenic environment to promote bone healing and repair. The primary workhorses of bone grafting includes autogenous bone, cadaver allograft, and bone graft substitutes. Among the first types of bone graft used and still used in large quantities today include autogenous and cadaver allograft bone. Allografts are useful because it is present in multiple forms that conform to the desired situation. But autogenous bone graft is considered the gold standard because it possesses all the fundamental properties to heal bone. However, it has been associated with high rates of donor site morbidity and typically requires an inpatient hospitalization following the procedure only adding to the associated costs. The first bone graft substitute use was calcium sulfate in 1892, and over the past 122 years advancements have achieved improved material properties of calcium sulfate and helped usher in additional bioceramics for bone grafting. Today there are predominantly 4 types of bioceramics available, which include calcium sulfate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. They come in multiple forms ranging from pellets and solid blocks to injectable and moldable putty. In comparison to autogenous bone graft, the primary limitation of bioceramics are the lack of osteogenic and osteoinductive properties. Bioceramics work by creating an osteoconductive scaffold to promote osteosynthesis. The options of bone graft substitutes don't end with these four types of bioceramics. Composite bioceramics take advantage of the differing biomechanical properties of these four basis types of bioceramics to develop improved materials. To overcome the lack of osteoinductive and osteogenic properties growth factors or bone marrow aspirate can be added to the bioceramic. As a result, the list of combinations available in our “biologic tool box” continues to expand. More than 20 BMPs have been identified, but only BMP-2 and BMP-7 have FDA approval. As we look forward to areas of future research and need within orthobiologics, some will likely come in the near future while others are much further in the future. We will continue to strive for the ideal bone graft substitute, which will have similar osteoinductive properties as autograft. The ultimate bone graft substitute will likely involve stem cells because it will allow an alternative to autogenous bone with the same osteogenic potential

Bone is a dynamic organ with remarkable regenerative properties seen only otherwise in the liver. However, bone healing requires vascularity, stability, growth factors, a matrix for growth, and viable cells to obtain effective osteosynthesis. We rely on these principles not only to heal fractures, but also achieve healing of benign bone defects. Unfortunately we are regularly confronted with situations where the local environment and tissue is insufficient and we must rely on our “biologic tool box.” When the process of bone repair requires additional assistance, we often look to bone grafting to provide an osteoconductive, osteoinductive, and/or osteogenic environment to promote bone healing and repair. The primary workhorses of bone grafting include autogenous bone, cadaver allograft, and bone graft substitutes. Among the first types of bone graft used and still used in large quantities today include autogenous and cadaver allograft bone. Allografts are useful because it is present in multiple forms that conform to the desired situation. But autogenous bone graft is considered the gold standard because it possesses all the fundamental properties to heal bone. However, it has been associated with high rates of donor site morbidity and typically requires an inpatient hospitalization following the procedure only adding to the associated costs. The first bone graft substitute use was calcium sulfate in 1892, and over the past 122 years advancements have achieved improved material properties of calcium sulfate and helped usher in additional bioceramics for bone grafting. Today there are predominantly 4 types of bioceramics available, which include calcium sulfate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. They come in multiple forms ranging from pellets and solid blocks to injectable and moldable putty. In comparison to autogenous bone graft, the primary limitation of bioceramics are the lack of osteogenic and osteoinductive properties. Bioceramics work by creating an osteoconductive scaffold to promote osteosynthesis. The options of bone graft substitutes don't end with these four types of bioceramics. Composite bioceramics take advantage of the differing biomechanical properties of these four basis types of bioceramics to develop improved materials. To overcome the lack of osteoinductive and osteogenic properties growth factors or bone marrow aspirate can be added to the bioceramic. As a result, the list of combinations available in our “biologic tool box” continues to expand. More than 20 BMPs have been identified, but only BMP-2 and BMP-7 have FDA approval. As we look forward to areas of future research and need within orthobiologics, some will likely come in the near future while others are much further in the future. We will continue to strive for the ideal bone graft substitute, which will have similar osteoinductive properties as autograft. The ultimate bone graft substitute will likely involve stem cells because it will allow an alternative to autogenous bone with the same osteogenic potential

Bone is a dynamic organ with remarkable regenerative properties seen only otherwise in the liver. However, bone healing requires vascularity, stability, growth factors, a matrix for growth, and viable cells to obtain effective osteosynthesis. We rely on these principles not only to heal fractures, but also achieve healing of benign bone defects. Unfortunately, we are regularly confronted with situations where the local environment and tissue is insufficient and we must rely on our “biologic tool box.” When the process of bone repair requires additional assistance, we often look to bone grafting to provide an osteoconductive, osteoinductive, and/or osteogenic environment to promote bone healing and repair. The primary workhorses of bone grafting include autogenous bone, cadaver allograft, and bone graft substitutes. Among the first types of bone graft used and still used in large quantities today include autogenous and cadaver allograft bone. Allografts are useful because they are present in multiple forms that conform to the desired situation. But autogenous bone graft is considered the gold standard because it possesses all the fundamental properties to heal bone. However, it has been associated with high rates of donor site morbidity and typically requires an inpatient hospitalization following the procedure only adding to the associated costs. The first bone graft substitute used was calcium sulfate in 1892, and over the past 122 years advancements have achieved improved material properties of calcium sulfate and helped usher in additional bioceramics for bone grafting. Today there are predominantly four types of bioceramics available, which include calcium sulfate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. They come in multiple forms ranging from pellets and solid blocks to injectable and moldable putty. In comparison to autogenous bone graft, the primary limitation of bioceramics are the lack of osteogenic and osteoinductive properties. Bioceramics work by creating an osteoconductive scaffold to promote osteosynthesis. The options of bone graft substitutes don't end with these four types of bioceramics. Composite bioceramics take advantage of the differing biomechanical properties of these four basis types of bioceramics to develop improved materials. To overcome the lack of osteoinductive and osteogenic properties growth factors or bone marrow aspirate can be added to the bioceramic. As a result, the list of combinations available in our “biologic tool box” continues to expand. More than 20 BMPs have been identified, but only BMP-2 and BMP-7 have FDA approval. As we look forward to areas of future research and need within orthobiologics, some will likely come in the near future while others are much further in the future. We will continue to strive for the ideal bone graft substitute, which will have similar osteoinductive properties as autograft. The ultimate bone graft substitute will likely involve stem cells because it will allow an alternative to autogenous bone with the same osteogenic potential

Although mechanical stabilisation has been a hallmark of orthopaedic surgical management, orthobiologics are now playing an increasing role. Platelet-rich plasma (PRP) is a volume of plasma fraction of autologous blood having platelet concentrations above baseline. The platelet α granules are rich in growth factors that play an essential role in tissue healing, such as transforming growth factor-β, vascular endothelial growth factor, and platelet-derived growth factor. PRP is used in various surgical fields to enhance bone and soft-tissue healing by placing supraphysiological concentrations of autologous platelets at the site of tissue damage. The easily obtainable PRP and its possible beneficial outcome hold promise for new regenerative treatment approaches. The aim of this literature review was to describe the bioactivities of PRP, to elucidate the different techniques for PRP preparation, to review animal and human studies, to evaluate the evidence regarding the use of PRP in trauma and orthopaedic surgery, to clarify risks, and to provide guidance for future research

Thirty years ago, rotator cuff surgery was exceedingly uncommon and shoulder arthroplasty almost unknown. Surgery for shoulder instability was largely empirical, non-anatomical and frequently unsuccessful. With the help of arthroscopy and MR scanning, a complex array of labral, ligament and tendon pathologies can now be recognised and treated, precisely and predictably. Anatomy-restoring arthroscopic techniques have largely replaced open stabilisation surgery. As life expectancy rises and citizens remain active into their seventh and eighth decades, the call for rotator cuff surgery has risen dramatically. Complex tendon transfers have expanded the indications for cuff surgery. Open repair has in part been supplanted by increasingly sophisticated arthroscopic techniques. The potential use of orthobiologics and stem cells promises further advances in the foreseeable future. Following the successful development of humeral hemiarthroplasty, and later of total shoulder replacement, surgical techniques and clinical indications for arthroplasty are now well refined. Predictable outcomes have been further enhanced by the present generation of ‘anatomic’ prostheses. More recently, the ‘rediscovery’ and improvement of semi-constrained (reverse) prostheses has transformed the previously dismal outlook for sufferers of cuff arthropathy and similar conditions. Many Australian Orthopaedic Association trainees undertake post-specialisation fellowships in shoulder surgery, both at home and abroad, and there is a steady flow of young overseas fellows through Australian shoulder units. The Shoulder and Elbow Society of Australia, founded in 1990 as a loose grouping of interested colleagues, now boasts over 70 active members. Australian surgeons and researchers are well represented in the prestigious Journal of Shoulder and Elbow Surgery and Australian shoulder surgery has come of age

Bone is a dynamic organ with remarkable regenerative properties seen only otherwise in the liver. However, bone healing requires vascularity, stability, growth factors, a matrix for growth, and viable cells to obtain effective osteosynthesis. We rely on these principles not only to heal fractures, but also achieve healing of benign bone defects. Unfortunately we are regularly confronted with situations where the local environment and tissue is insufficient and we must rely on our “biologic tool box.” When the process of bone repair requires additional assistance, we often look to bone grafting to provide an osteoconductive, osteoinductive, and/or osteogenic environment to promote bone healing and repair. The primary workhorses of bone grafting includes autogenous bone, cadaver allograft, and bone graft substitutes. Among the first types of bone graft used and still used in large quantities today include autogenous and cadaver allograft bone. Allografts are useful because it is present in multiple forms that conform to the desired situation. But autogenous bone graft is considered the gold standard because it possesses all the fundamental properties to heal bone. However, it has been associated with high rates of donor site morbidity and typically requires an inpatient hospitalization following the procedure only adding to the associated costs. The first bone graft substitute use was calcium sulfate in 1892, and over the past 122 years advancements have achieved improved material properties of calcium sulfate and helped usher in additional bioceramics for bone grafting. Today there are predominantly 4 types of bioceramics available, which include calcium sulfate, calcium phosphate, tricalcium phosphate, and coralline hydroxyapatite. They come in multiple forms ranging from pellets and solid blocks to injectable and moldable putty. In comparison to autogenous bone graft, the primary limitation of bioceramics are the lack of osteogenic and osteoinductive properties. Bioceramics work by creating an osteoconductive scaffold to promote osteosynthesis. The options of bone graft substitutes don't end with these four types of bioceramics. Composite bioceramics take advantage of the differing biomechanical properties of these four basis types of bioceramics to develop improved materials. To overcome the lack of osteoinductive and osteogenic properties growth factors or bone marrow aspirate can be added to the bioceramic. As a result, the list of combinations available in our “biologic tool box” continues to expand. More than 20 BMPs have been identified, but only BMP-2 and BMP-7 have FDA approval. As we look forward to areas of future research and need within orthobiologics, some will likely come in the near future while others are much further in the future. We will continue to strive for the ideal bone graft substitute, which will have similar osteoinductive properties as autograft. The ultimate bone graft substitute will likely involve stem cells because it will allow an alternative to autogenous bone with the same osteogenic potential