| The Use of Biological Approaches in the Treatment of Shoulder Pathology A Critical Analysis Review Jonas Pogorzelski, MD, MHBA Abstract » The major pathological conditions affecting the shoulder that are Jonathan A. Godin, MD, MBA treated with use of biological applications include focal cartilage Erik M. Fritz, MD lesions and rotator cuff tears. Biological modalities that previously have been used or investigated include platelet-rich plasma (PRP), growth Mark E. Cinque, MS factors, progenitor cells, bone-marrow stimulation, autologous chon- Jorge Chahla, MD drocyte implantation (ACI), matrix-induced ACI (MACI), and biological scaffolds. Johnny Huard, PhD Peter J. Millett, MD, MSc » Marrow-stimulating procedures have been reported to yield positive results when used for the treatment of focal cartilage lesions of the glenoid or humeral head. Limited data are available on the use of PRP, Investigation performed at the ACI, and MACI for the treatment of chondral lesions involving the Steadman Philippon Research shoulder, and therefore no conclusions can be drawn regarding the Institute, Vail, Colorado efficacy of these modalities. » Preclinical and in vitro studies have demonstrated that modulation of growth factors may be helpful for rotator cuff tear healing; however, the optimal modulation and delivery vehicle remain to be elucidated. PRP has received much research attention; however, most studies have been hindered by study setup and conflicting results. Therefore, the use of PRP to enhance rotator cuff healing remains controversial. Progenitor cells have shown positive results in a small number of preclinical and clinical studies, but further research is needed before conclusions can be drawn. » In summary, basic-science studies investigating biological factors to enhance healing in the shoulder have shown potential. However, clinical data are still limited, contradictory, and controversial. Addi- tional research is needed. Most importantly, robust, consistent, well- powered clinical trials are necessary to definitively determine which methods improve clinical outcomes. houlder pain is the second most However, because of increasing patient age common musculoskeletal com- and the rising number of active patients, plaint encountered in primary there is a demand for improved treatment care offices, occurring in about of all shoulder abnormalities. Therefore, 51%S of patients1. Over the last few years, the use of orthobiologics in shoulder sur- major advances have been made in both the gery has expanded rapidly over the past operative and nonoperative treatment of decade. Some of the commonly used shoulder pain and pathological conditions. biologics in shoulder surgery include Disclosure: No funding was received during the preparation or execution of this manuscript. On the Disclosure of Potential Conflicts of Interest which are provided with the online version of the COPYRIGHT © 2017 BY THE forms, JOURNAL OF BONE AND JOINT article, one or more of the authors checked “yes” to indicate that the author had a relevant financial SURGERY, INCORPORATED relationship in the biomedical arena outside the submitted work (http://links.lww.com/JBJSREV/A265). JBJS REVIEWS 2017;5(9):e5 · http://dx.doi.org/10.2106/JBJS.RVW.17.00035 1 | The Use of Biological Approaches in the Treatment of Shoulder Pathology progenitor cells, growth factors, platelet- contained cartilage lesions. The aim of of the patients stated that they would rich plasma (PRP), and biological this technique is to perforate the sub- have the surgery again. Last, Siebold and matrices. The potential advantages of chondral bone to promote the release colleagues11 reported significant im- biological augmentation of traditional of progenitor cells and multiple growth provements in pain and functional shoulder surgical techniques include factors to the chondral defect. Under scores (p 5 0.0053 and p 5 0.018, minimal invasiveness, improved healing favorable mechanical-stress character- respectively) in patients managed capacity, and more-rapid recovery. istics (stress-free joint movement with with microfracture combined with a Conversely, the use of biologics is cur- varying pressure, tensile, and shearing periosteal flap. Poor prognostic predic- rently expensive, and the evidence of forces), these progenitor cells will dif- tors included prior surgery and, poten- long-term effectiveness is limited. Fur- ferentiate into fibrochondrocytes, ul- tially, lesion size, although the results thermore, the body of literature on the timately creating a fibrocartilage layer. were not significant. use and efficacy of biologics in shoulder However, the higher content of type-I surgery is heterogeneous with regard to collagen makes this repair tissue one of Platelet-Rich Plasma (PRP) indications, therapies, processing lesser biomechanical quality than hy- PRP has been widely utilized for the methods, and inoculation. Although aline cartilage, as previously reported treatment of various musculoskeletal some studies have demonstrated en- in animal experiments3. Patient selec- conditions or as an augmentation tool couraging results following either iso- tion is most certainly key for successful on the basis of basic-science and lated treatment with biologics or outcomes. However, clear indications emerging clinical studies12,13.Thebi- biologic-augmented surgery, other are not available in the shoulder liter- ological reasoning behind the clinical studies have failed to demonstrate sub- ature; therefore, on the basis of an al- use of PRP includes local delivery of stantial benefit. Given the heterogeneity gorithm that has been extrapolated growth factors, modification of the in- and paucity of critical analyses within from the knee literature, microfracture flammatory response, increased hemo- the literature, the objective of the is considered to be suitable for the stasis, and positive effects on cell present review is to evaluate the value treatment of small, circumscribed car- proliferation and differentiation14-17. of orthobiologics in the treatment of tilage defects (maximum, 4 cm2)with Although symptomatic relief has been shoulder pathologies. More precisely, intact subchondral bone in young, ac- reported following the use of PRP for we aim to perform a balanced evaluation tive patients4-7. the treatment of early-stage knee oste- of biologic augmentation of existing In general, better results have oarthritis14, we are not aware of any modalities for the treatment of focal been reported for small unipolar de- studies that have evaluated the efficacy chondral defects, osteoarthritis, and ro- fects on either the glenoid or humeral of PRP in the shoulder. However, au- tator cuff tears. side, whereas the worst results have tologous platelet-poor plasma and been seen in association with bipolar platelet gel have been shown to reduce Focal Chondral Defects and glenohumeral lesions2,3,8.Millett pain scores and to yield significantly Glenohumeral Osteoarthritis et al., in a study of 31 shoulders, better functional outcomes (internal A trial of conservative therapy consisting reported significant (p , 0.05) reduc- rotation, p , 0.05) following total of physical therapy and nonsteroidal tion in pain and improvement in shoulder arthroplasty18.Inthestudyby anti-inflammatory medications is typi- function according to the American Lo et al.19, 55 patients with glenohu- cally seen as the primary treatment when Shoulder and Elbow Surgeons (ASES) meral arthritis were managed with a a symptomatic cartilage defect is iden- score9 at a mean of 4 years after the use biologically based resurfacing arthro- tified in the shoulder2. If symptoms of microfracture for the treatment of plasty with use of acellular human persist, biologic-based treatments such full-thickness articular cartilage in- dermal allograft in combination with as marrow-stimulation procedures, juries. Only 19% of the patients in that PRP. After an average duration of bone marrow aspirate concentrate cohort were considered to have had a follow-upof60months,theaverage (BMAC), PRP, and cell-based therapies failure requiring additional surgery2. ASES score was 76 6 22, the average such as autologous chondrocyte im- Likewise, Frank and colleagues, in a Western Ontario Osteoarthritis of the plantation (ACI) or matrix-induced ACI series of 16 patients (17 shoulders), Shoulder (WOOS) index was 76% 6 (MACI) can be used. reported significant improvement in 22%,andtheaverage visualanalogscale shoulder function as demonstrated by (VAS) score for pain was 2.4 6 2.6, Microfracture an increase in the Simple Shoulder Test with an 81% rate of patient satisfaction. The microfracture procedure has been (SST) and ASES scores (p , 0.01 for The average joint space increased from widely used in several joints because of both) and significant pain reduction 1 6 1 mm preoperatively to 2 6 1mm its ease of performance, low cost, and (p , 0.01) at .2 years postoperatively10. postoperatively. Fewer than 10% of the overall positive reported outcomes Outcomes did not significantly vary patients underwent revision to total when used for the treatment of small, with respect to sex or age. Of note, 93% shoulder arthroplasty. 2 SEPTEMBER 2017 · VOLUME 5, ISSUE 9 · e5 The Use of Biological Approaches in the Treatment of Shoulder Pathology | Autologous Chondrocyte improve the regeneration of the native mesenchymal stromal cells (MSCs), Implantation (ACI) and Matrix- cuff insertion site, and to inhibit the platelets, and growth factors. However, Induced ACI (MACI) formation of