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University of Maryland is the region’s only academic medical center currently implementing regenerative medicine techniques into their orthopaedic clinical practices to safely treat chronic musculoskeletal pain that has not successfully responded to traditional therapies.

Because they leverage the body’s own healing powers to treat common musculoskeletal conditions such as osteoarthritis and tendinopathy, regenerative procedures are showing greater efficacy in managing these conditions compared to the currently standard nonsurgical treatments such as NSAIDs and corticosteroids. Moreover, these standard treatments are replete with risks; NSAIDS have been linked with cardiovascular events, and corticosteroids are chondrotoxic and raise blood sugar in patients with diabetes. While providing short-term pain relief, standard approaches should also be used with caution in patients with tendinopathy because NSAIDS may impair the proliferation and differentiation of tenocytes, negatively affecting tendon healing, and corticosteroids can lead to tenocyte death and tendon rupture. Corticosteroids may also be problematic for treating osteoarthritis; some studies have demonstrated dose-dependent deleterious effects on cartilage morphology, histology and viability in both in vitro and in vivo models.

As a complement to other traditional therapies such as rest, bracing, taping and physical therapy, physicians at University of Maryland Orthopaedics are employing regenerative medicine techniques to help more patients avoid surgery and live pain-free lives. The four regenerative medicine approaches currently used at University of Maryland Orthopedics include dextrose prolotherapy, platelet-rich plasma, amniotic tissue allografts and adipose-derived mesenchymal stem cells, which are explained briefly below.

Synthetic Orthobiologics Provided Through Dextrose Prolotherapy

Prolotherapy, a portmanteau of “proliferative therapy,” is a method of injecting irritant solutions – usually 50% dextrose plus saline and lidocaine – to stimulate the body’s healing processes. It is thought to work because dextrose levels greater than 10% produce an osmotic effect that stimulates cell shrinkage through leakage of lipids, which causes temporary inflammation. This, in turn, creates a natural growth factor elevation of TGF-β, IGF-1, PDGF as well as a needling effect that leads to cell membrane and small blood vessel disruption that recruits platelets to the healing site. Growth factors help to promote collagen expression and synthesis as well as cause anabolic and anti catabolic effects that can lead to cartilage repair. Prolotherapy also targets and destroys some pain-causing signals. Injections can be inserted into a joint space, ligament or tendon, although the focus is on treating an entire region.

Many conditions respond well to prolotherapy, including arthritis, tendon or muscle strains, and joint or ligament sprains, among others. Prolotherapy has a better track record than traditional corticosteroid injections of lasting, and sometimes permanent, pain relief. While a study comparing the two modalities demonstrated greater pain relief for steroid injections at one month after treatment, by two months they were comparable, and by six months the patients who had received prolotherapy had less pain.1

Patients’ Own Platelet-Rich Plasma Applied to Their Injuries

Platelet-rich plasma, or PRP, is a treatment first developed more than three decades ago by the equestrian industry and later adopted for human application first by dentistry. It involves the creation of an autologous blood product through drawing a patient’s blood, spinning it down in a centrifuge and then extracting only the platelet-rich plasma to inject back into the symptomatic tissue or joint. The injection may be guided by additional imaging with an X-ray or ultrasound to ensure the PRP reaches its intended target. The entire process can be completed in the same patient visit.

This modality works because PRP releases growth factors that stimulate a healing cascade by promoting cartilage matrix synthesis, increasing cell growth and migration, and facilitating protein translation. A study comparing PRP injections to hyaluronic acid (HA) injections showed that while both treatments produced no adverse results, PRP led to better pain relief and increased function compared to HA at 6 and 12 months.2

Dehydrated Human Amnion/Chorion Membrane (dHACM) to Produce Collagen and Pain Relief

Previously used primarily for surgical wound healing, amniotic membrane tissue procured from donor placentas during planned C-sections is sterilized and dehydrated to be micronized into a powder that can be injected into joints and soft tissue. While no stem cells are present, the amniotic membrane contains more than 225 different natural growth factors, cytokines, chemokines and collagens that can help the body modulate inflammation and enhance healing of musculoskeletal injuries. 

Dehydrated human amnion/chorion membrane injections are a useful alternative to PRP, especially in the geriatric population who may not have a robust collection of healing factors in their own blood. In a study of 40 patients, it was found that dHACM produced pain relief in 68% at one month, 82% at two months and 91% at three months.3

Adipose-Derived Mesenchymal Stem Cells (ADMSC) to Create an Environment for Healing

The only orthobiologic technique currently available at the University of Maryland that uses stem cells is the micro-fragmented adipose tissue procedure, performed in a medical office or surgical center. Adipose tissue, a small quantity of which can be procured from patients’ own abdominal regions through mini-liposuction, contains a high concentration of mesenchymal stem cells (MSCs). MSCs are adult stem cells thought to be able to be differentiated into fat, cartilage and bone, although this differentiation feature is not activated in this particular treatment. Rather, these harvested cells, the quantity and quality of which may be influenced by the age and health of the patient, are processed and injected with extracellular matrix proteins and growth factors, which promote healing. The MSCs merely act as a stimulus that activates the cells and growth factors that are already present at the treatment site.

Adipose tissue cells can be injected to treat a multitude of orthopaedic conditions. A study of 38 patients with osteoarthritis found that all of them were satisfied with the ASMSC procedure, 92% of them having experienced clinical improvement.4

With all of these modalities, some soreness after the procedure is expected, but many patients return to work or their regular activities on the day of the procedure. One injection may be all that is needed to provide significant benefit, but the procedures can be repeated or another regenerative approach tried if necessary.

Physicians from University of Maryland Orthopaedics are board certified and fellowship-trained. As part of an academic medical center, they are heavily involved in research and teaching in addition to clinical care.

To refer a patient, call 410-448-6400 or visit umortho.org for more information.

Schedule Grand Rounds for your hospital with our orthopaedic physicians or surgeons.

1Jahangiri A, Moghaddam  FR, Najafi S. Hypertonic dextrose versus corticosteroid local injection for the treatment of osteoarthritis in the first carpometacarpal joint: a double-blind randomized clinical trial. J Orthop Sci. 2014 Sep;19(5):737-43. doi: 10.1007/s00776-014-0587-2.
2  Han Y, Huang H, Pan J, Lin J, Zeng L, Liang G, Yang W, Liu J. Meta-analysis comparing platelet-rich plasma vs hyaluronic acid injection in patients with knee osteoarthritis. Pain Med. 2019 Mar 7. pii: pnz011. doi: 10.1093/pm/pnz011.
3Gellhorn AC, Han A. The use of dehydrated human amnion/chorion membrane allograft injection for the treatment of tendinopathy or arthritis: a case series involving 40 patients. PM R. 2017 Dec;9(12):1236-1243. doi: 10.1016/j.pmrj.2017.04.011.
4Cattaneo G, De Caro A, Napoli F, Chiapale D, Trada P, Camera A. Micro-fragmented adipose tissue injection associated with arthroscopic procedures in patients with symptomatic knee osteoarthritis. BMC Musculoskelet Disord. 2018 May 30;19(1):176. doi: 10.1186/s12891-018-2105-8.

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